Allosteric SHP2 inhibitors in cancer: Targeting the intersection of RAS, resistance, and the immune microenvironment

Cell Signaling by Receptor Tyrosine Kinases

Lemmon, M. A., & Schlessinger, J. (2010) · Cell · doi:10.1016/j.cell.2010.06.011 · Cited by 7,929 · see citing works

Understanding the tumor immune microenvironment (TIME) for effective therapy

Binnewies, M., Roberts, E. W., Kersten, K., Chan, V., Fearon, D. F., Merad, M., Coussens, L. M., Gabrilovich, D. I., Ostrand-Rosenberg, S., Hedrick, C. C., et al. (2018) · Nature Medicine · doi:10.1038/s41591-018-0014-x · Cited by 6,145 · see citing works

Cell Signaling by Receptor Tyrosine Kinases

Schlessinger, J. (2000) · Cell · doi:10.1016/s0092-8674(00)00114-8 · Cited by 3,774 · see citing works

RAS Proteins and Their Regulators in Human Disease

Simanshu, D. K., Nissley, D. V., & McCormick, F. (2017) · Cell · doi:10.1016/j.cell.2017.06.009 · Cited by 1,943 · see citing works

T cell costimulatory receptor CD28 is a primary target for PD-1–mediated inhibition

Hui, E., Cheung, J., Zhu, J., Su, X., Taylor, M. J., Wallweber, H. A., Sasmal, D. K., Huang, J., Kim, J. M., Mellman, I., et al. (2017) · Science · doi:10.1126/science.aaf1292 · Cited by 1,689 · see citing works

Dabrafenib plus trametinib in patients with previously untreated BRAFV600E-mutant metastatic non-small-cell lung cancer: an open-label, phase 2 trial

Planchard, D., Smit, E. F., Groen, H. J. M., Mazières, J., Besse, B., Helland, Å., Giannone, V., D'amelio, A. M., Zhang, P., Mookerjee, B., et al. (2017) · The Lancet Oncology · doi:10.1016/s1470-2045(17)30679-4 · Cited by 1,360 · see citing works

The ‘Shp'ing news: SH2 domain-containing tyrosine phosphatases in cell signaling

Neel, B. G., Gu, H., & Pao, L. (2003) · Trends in Biochemical Sciences · doi:10.1016/s0968-0004(03)00091-4 · Cited by 1,249 · see citing works

RAS-targeted therapies: is the undruggable drugged?

Moore, A. R., Rosenberg, S. C., McCormick, F., & Malek, S. (2020) · Nature Reviews Drug Discovery · doi:10.1038/s41573-020-0068-6 · Cited by 1,103 · see citing works

Understanding and targeting resistance mechanisms in NSCLC

Rotow, J. K., & Bivona, T. G. (2017) · Nature reviews. Cancer · doi:10.1038/nrc.2017.84 · Cited by 978 · see citing works

Allosteric inhibition of SHP2 phosphatase inhibits cancers driven by receptor tyrosine kinases

Chen, Y.-N. P., LaMarche, M. J., Chan, H. M., Fekkes, P., Garcia-Fortanet, J., Acker, M. G., Antonakos, B., Chen, C. H.-T., Chen, Z., Cooke, V. G., et al. (2016) · Nature · doi:10.1038/nature18621 · Cited by 925 · see citing works

PD‐1 inhibits T‐cell receptor induced phosphorylation of the ZAP70/CD3ζ signalosome and downstream signaling to PKCθ

Sheppard, K.-A., Fitz, L. J., Lee, J. M., Benander, C., George, J. A., Wooters, J., Qiu, Y., Jussif, J. M., Carter, L. L., Wood, C. R., et al. (2004) · FEBS Letters · doi:10.1016/j.febslet.2004.07.083 · Cited by 791 · see citing works

Biochemical and Structural Analysis of Common Cancer-Associated KRAS Mutations

Hunter, J. C., Manandhar, A., Carrasco, M. A., Gurbani, D., Gondi, S., & Westover, K. D. (2015) · Molecular Cancer Research · doi:10.1158/1541-7786.mcr-15-0203 · Cited by 786 · see citing works

Protein tyrosine phosphatases in signal transduction

Neel, B. G., & Tonks, N. K. (1997) · Current Opinion in Cell Biology · doi:10.1016/s0955-0674(97)80063-4 · Cited by 757 · see citing works

Allele-specific inhibitors inactivate mutant KRAS G12C by a trapping mechanism

Lito, P., Solomon, M., Li, L.-S., Hansen, R., & Rosen, N. (2016) · Science · doi:10.1126/science.aad6204 · Cited by 691 · see citing works

Molecular Basis of T Cell Inactivation by CTLA-4

Lee, K.-M., Chuang, E., Griffin, M., Khattri, R., Hong, D. K., Zhang, W., Straus, D., Samelson, L. E., Thompson, C. B., & Bluestone, J. A. (1998) · Science · doi:10.1126/science.282.5397.2263 · Cited by 684 · see citing works

The allosteric inhibitor ABL001 enables dual targeting of BCR–ABL1

Wylie, A. A., Schoepfer, J. G., Jahnke, W., Cowan‐Jacob, S. W., Loo, A. T., Furet, P., Marzinzik, A. L., Pellé, X., Donovan, J., Zhu, W. S., et al. (2017) · Nature · doi:10.1038/nature21702 · Cited by 622 · see citing works

MEK1 and MEK2 inhibitors and cancer therapy: the long and winding road

Caunt, C. J., Sale, M. J., Smith, P. D., & Cook, S. J. (2015) · Nature Reviews Cancer · doi:10.1038/nrc4000 · Cited by 606 · see citing works

Combination Cancer Therapy with Immune Checkpoint Blockade: Mechanisms and Strategies

Patel, S. A., & Minn, A. J. (2018) · Immunity · doi:10.1016/j.immuni.2018.03.007 · Cited by 574 · see citing works

Sprouty1 and Sprouty2 provide a control mechanism for the Ras/MAPK signalling pathway

Hanafusa, H., Torii, S., Yasunaga, T., & Nishida, E. (2002) · Nature Cell Biology · doi:10.1038/ncb867 · Cited by 566 · see citing works

Tumours with class 3 BRAF mutants are sensitive to the inhibition of activated RAS

Yao, Z., Yaeger, R., Rodrik-Outmezguine, V. S., Tao, A., Torres, N. M., Chang, M. T., Drosten, M., Zhao, H., Cecchi, F., Hembrough, T., et al. (2017) · Nature · doi:10.1038/nature23291 · Cited by 562 · see citing works

Rapid non-uniform adaptation to conformation-specific KRAS(G12C) inhibition

Xue, J. Y., Zhao, Y., Aronowitz, J., Mai, T. T., Vides, A., Qeriqi, B., Kim, D., Li, C., de Stanchina, E., Mazutis, L., et al. (2020) · Nature · doi:10.1038/s41586-019-1884-x · Cited by 543 · see citing works

Targeting ALK: Precision Medicine Takes on Drug Resistance

Lin, J. J., Riely, G. J., & Shaw, A. T. (2017) · Cancer Discovery · doi:10.1158/2159-8290.cd-16-1123 · Cited by 528 · see citing works

Activating Mutations of the Noonan Syndrome-Associated <b> <i>SHP2/PTPN11</i> </b> Gene in Human Solid Tumors and Adult Acute Myelogenous Leukemia

Bentires-Alj, M., Paez, J. G., David, F. S., Keilhack, H., Halmos, B., Naoki, K., Maris, J. M., Richardson, A., Bardelli, A., Sugarbaker, D. J., et al. (2004) · Cancer Research · doi:10.1158/0008-5472.can-04-1923 · Cited by 509 · see citing works

Inside the human cancer tyrosine phosphatome

Julien, S. G., Dubé, N., Hardy, S., & Tremblay, M. L. (2010) · Nature reviews. Cancer · doi:10.1038/nrc2980 · Cited by 498 · see citing works

Vertical Pathway Inhibition Overcomes Adaptive Feedback Resistance to KRASG12C Inhibition

Ryan, M. B., Fece de la Cruz, F., Phat, S., Myers, D. T., Wong, E., Shahzade, H. A., Hong, C. B., & Corcoran, R. B. (2020) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-19-3523 · Cited by 496 · see citing works

Shp2 regulates SRC family kinase activity and Ras/Erk activation by controlling Csk recruitment.

Zhang, S.-Q., Yang, W., Kontaridis, M. I., Bivona, T., Wen, G., Araki, T., Luo, J.-C., Thompson, J. A., Schraven, B., Philips, M., et al. (2004) · Molecules and Cells · doi:10.1016/s1097-2765(04)00050-4 · Cited by 470 · see citing works

Spred is a Sprouty-related suppressor of Ras signalling

Wakioka, T., Sasaki, A. T., Kato, R., Shouda, T., Matsumoto, A., Miyoshi, K., Tsuneoka, M., Komiya, S., Baron, R., & Yoshimura, A. (2001) · Nature · doi:10.1038/35088082 · Cited by 446 · see citing works

Dissecting the mechanisms of immune checkpoint therapy

Sharma, P., & Allison, J. P. (2020) · Nature reviews. Immunology · doi:10.1038/s41577-020-0275-8 · Cited by 438 · see citing works

RAS nucleotide cycling underlies the SHP2 phosphatase dependence of mutant BRAF-, NF1- and RAS-driven cancers

Nichols, R. J., Haderk, F., Stahlhut, C., Schulze, C. J., Hemmati, G., Wildes, D., Tzitzilonis, C., Mordec, K., Marquez, A., Romero, J., et al. (2018) · Nature Cell Biology · doi:10.1038/s41556-018-0169-1 · Cited by 415 · see citing works

The tyrosine phosphatase Shp2 (PTPN11) in cancer

Chan, G., Kalaitzidis, D., & Neel, B. G. (2008) · Cancer and Metastasis Reviews · doi:10.1007/s10555-008-9126-y · Cited by 386 · see citing works

A model for RAS mutation patterns in cancers: finding the sweet spot

Li, S., Balmain, A., & Counter, C. M. (2018) · Nature Reviews Cancer · doi:10.1038/s41568-018-0076-6 · Cited by 384 · see citing works

KRAS Alleles: The Devil Is in the Detail

Haigis, K. M. (2017) · Trends in Cancer · doi:10.1016/j.trecan.2017.08.006 · Cited by 373 · see citing works

Mutant KRAS-driven cancers depend on PTPN11/SHP2 phosphatase

Ruess, D. A., Heynen, G. J., Ciecielski, K. J., Ai, J., Berninger, A., Kabacaoglu, D., Görgülü, K., Dantes, Z., Wörmann, S. M., Diakopoulos, K. N., et al. (2018) · Nature Medicine · doi:10.1038/s41591-018-0024-8 · Cited by 370 · see citing works

Recent advances in RASopathies

Aoki, Y., Niihori, T., Inoue, S., & Matsubara, Y. (2015) · Journal of Human Genetics · doi:10.1038/jhg.2015.114 · Cited by 369 · see citing works

The molecular functions of Shp2 in the Ras/Mitogen-activated protein kinase (ERK1/2) pathway

Dance, M., Montagner, A., Salles, J.-P., Yart, A., & Raynal, P. (2008) · Cellular Signalling · doi:10.1016/j.cellsig.2007.10.002 · Cited by 361 · see citing works

Selumetinib Plus Docetaxel Compared With Docetaxel Alone and Progression-Free Survival in Patients With <i>KRAS</i> -Mutant Advanced Non–Small Cell Lung Cancer: The SELECT-1 Randomized Clinical Trial

Jänne, P. A., van den Heuvel, M. M., Barlesi, F., Cobo, M., Mazieres, J., Crinò, L., Orlov, S., Blackhall, F., Wolf, J., Garrido, P., et al. (2017) · JAMA · doi:10.1001/jama.2017.3438 · Cited by 335 · see citing works

Revealing mechanisms for SH2 domain mediated regulation of the protein tyrosine phosphatase SHP-2

Barford, D., & Neel, B. G. (1998) · Structure · doi:10.1016/s0969-2126(98)00027-6 · Cited by 321 · see citing works

SHP2 is required for growth of KRAS-mutant non-small-cell lung cancer in vivo

Mainardi, S., Mulero-Sánchez, A., Prahallad, A., Germano, G., Bosma, A., Krimpenfort, P., Lieftink, C., Steinberg, J. D., de Wit, N., Gonçalves-Ribeiro, S., et al. (2018) · Nature Medicine · doi:10.1038/s41591-018-0023-9 · Cited by 320 · see citing works

SHP2 inhibition prevents adaptive resistance to MEK inhibitors in multiple cancer models

Fedele, C., Ran, H., Diskin, B., Wei, W., Jen, J., Geer, M. J., Araki, K., Ozerdem, U., Simeone, D. M., Miller, G., et al. (2018) · Cancer Discovery · doi:10.1158/2159-8290.cd-18-0444 · Cited by 315 · see citing works

Molecular mechanism for a role of SHP2 in epidermal growth factor receptor signaling

Agazie, Y. M., & Hayman, M. J. (2003) · Molecular and Cellular Biology · doi:10.1128/mcb.23.21.7875-7886.2003 · Cited by 306 · see citing works

Allosteric inhibition of SHP2: identification of a potent, selective, and orally efficacious phosphatase inhibitor

Garcia Fortanet, J., Chen, C. H.-T., Chen, Y.-N. P., Chen, Z., Deng, Z., Firestone, B., Fekkes, P., Fodor, M., Fortin, P. D., Fridrich, C., et al. (2016) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.6b00680 · Cited by 298 · see citing works

Loss of NF1 in cutaneous melanoma is associated with RAS activation and MEK dependence

Nissan, M. H., Pratilas, C., Jones, A. M., Ramirez, R., Won, H., Liu, C.-L., Tiwari, S., Kong, L., Hanrahan, A. J., Yao, Z., et al. (2014) · Cancer Research · doi:10.1158/0008-5472.can-13-2625 · Cited by 297 · see citing works

The Tyrosine Phosphatase Shp2 in Development and Cancer

(2010) · Advances in Cancer Research · doi:10.1016/s0065-230x(10)06002-1 · Cited by 277 · see citing works

Site-Specific Incorporation of a Phosphotyrosine Mimetic Reveals a Role for Tyrosine Phosphorylation of SHP-2 in Cell Signaling

Lu, W., Gong, D., Bar-Sagi, D., & Cole, P. A. (2001) · Molecular Cell · doi:10.1016/s1097-2765(01)00369-0 · Cited by 268 · see citing works

Molecular mechanism of SHP2 activation by PD-1 stimulation

Marasco, M., Berteotti, A., Weyershaeuser, J., Thorausch, N., Sikorska, J., Krausze, J., Brandt, H., Kirkpatrick, J., Ríos, P., Schamel, W. W. A., et al. (2020) · Science Advances · doi:10.1126/sciadv.aay4458 · Cited by 268 · see citing works

Phase Separation of Disease-Associated SHP2 Mutants Underlies MAPK Hyperactivation

Zhu, G., Xie, J., Kong, W., Xie, J., Li, Y., Du, L., Zheng, Q., Sun, L., Guan, M., Li, H., et al. (2020) · Cell · doi:10.1016/j.cell.2020.09.002 · Cited by 267 · see citing works

Targeting wild-type KRAS-amplified gastroesophageal cancer through combined MEK and SHP2 inhibition

Wong, G. S., Zhou, J., Liu, J. B., Wu, Z., Xu, X., Li, T., Xu, D., Schumacher, S. E., Puschhof, J., McFarland, J., et al. (2018) · Nature Medicine · doi:10.1038/s41591-018-0022-x · Cited by 266 · see citing works

SHP2 inhibition diminishes KRASG12C cycling and promotes tumor microenvironment remodeling

Fedele, C., Li, S., Teng, K. W., Foster, C. J. R., Peng, D., Ran, H., Mita, P., Geer, M. J., Hattori, T., Koide, A., et al. (2021) · Journal of Experimental Medicine · doi:10.1084/jem.20201414 · Cited by 265 · see citing works

NMR-based functional profiling of RASopathies and oncogenic RAS mutations

Smith, M. J., Neel, B. G., & Ikura, M. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1218173110 · Cited by 257 · see citing works

Handbook of Cell Signaling

(2010) · Elsevier eBooks · doi:10.1016/b978-0-12-374145-5.x0001-0 · Cited by 257 · see citing works

Visualization of the Cysteinyl-phosphate Intermediate of a Protein-tyrosine Phosphatase by X-ray Crystallography

Pannifer, A., Flint, A. J., Tonks, N. K., & Barford, D. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.17.10454 · Cited by 237 · see citing works

Tyrosyl phosphorylation of Shp2 is required for normal ERK activation in response to some, but not all, growth factors

Araki, T., Nawa, H., & Neel, B. G. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m306461200 · Cited by 231 · see citing works

Identification of TNO155, an Allosteric SHP2 Inhibitor for the Treatment of Cancer

LaMarche, M. J., Acker, M., Argintaru, A., Bauer, D., Boisclair, J., Chan, H., Chen, C. H.-T., Chen, Y.-N., Chen, Z., Deng, Z., et al. (2020) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.0c01170 · Cited by 231 · see citing works

SHP2 drives adaptive resistance to ERK signaling inhibition in molecularly defined subsets of ERK-dependent tumors

Ahmed, T. A., Adamopoulos, C., Karoulia, Z., Wu, X., Sachidanandam, R., Aaronson, S. A., & Poulikakos, P. I. (2019) · Cell Reports · doi:10.1016/j.celrep.2018.12.013 · Cited by 214 · see citing works

A Novel Role for Gab1 and SHP2 in Epidermal Growth Factor-induced Ras Activation

Montagner, A., Yart, A., Dance, M., Perret, B., Salles, J., & Raynal, P. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m410012200 · Cited by 205 · see citing works

Spatial constraints on the recognition of phosphoproteins by the tandem SH2 domains of the phosphatase SH-PTP2

Eck, M. J., Pluskey, S., Trüb, T., Harrison, S. C., & Shoelson, S. E. (1996) · Nature · doi:10.1038/379277a0 · Cited by 199 · see citing works

SHP2 inhibition restores sensitivity in ALK-rearranged non-small-cell lung cancer resistant to ALK inhibitors

Dardaei, L., Wang, H. Q., Singh, M., Fordjour, P., Shaw, K. X., Yoda, S., Kerr, G., Yu, K., Liang, J., Cao, Y., et al. (2018) · Nature Medicine · doi:10.1038/nm.4497 · Cited by 199 · see citing works

SHP2 inhibition triggers anti-tumor immunity and synergizes with PD-1 blockade

Zhao, M., Guo, W., Wu, Y., Yang, C., Zhong, L., Deng, G., Zhu, Y., Liu, W., Gu, Y., Lu, Y., et al. (2019) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2018.08.009 · Cited by 190 · see citing works

A framework for understanding and targeting residual disease in oncogene-driven solid cancers

Bivona, T. G., & Doebele, R. C. (2016) · Nature Medicine · doi:10.1038/nm.4091 · Cited by 176 · see citing works

KRAS ^G12C inhibition produces a driver-limited state revealing collateral dependencies

Lou, K., Steri, V., Ge, A. Y., Hwang, Y. C., Yogodzinski, C. H., Shkedi, A. R., Choi, A. L. M., Mitchell, D. C., Swaney, D. L., Hann, B., et al. (2019) · Science Signaling · doi:10.1126/scisignal.aaw9450 · Cited by 175 · see citing works

Discovery of SHP2-D26 as a First, Potent, and Effective PROTAC Degrader of SHP2 Protein

Wang, M., Lu, J., Wang, M., Yang, C.-Y., & Wang, S. (2020) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.0c00471 · Cited by 172 · see citing works

Roles of Gab1 and SHP2 in Paxillin Tyrosine Dephosphorylation and Src Activation in Response to Epidermal Growth Factor

Ren, Y., Meng, S., Mei, L., Zhao, Z. J., Jove, R., & Wu, J. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m312575200 · Cited by 171 · see citing works

PTPN11 is a central node in intrinsic and acquired resistance to targeted cancer drugs

Prahallad, A., Heynen, G. J. J. E., Germano, G., Willems, S. M., Evers, B., Vecchione, L., Gambino, V., Lieftink, C., Beijersbergen, R. L., Di Nicolantonio, F., et al. (2015) · Cell Reports · doi:10.1016/j.celrep.2015.08.037 · Cited by 168 · see citing works

Structural reorganization of SHP2 by oncogenic mutations and implications for oncoprotein resistance to allosteric inhibition

LaRochelle, J. R., Fodor, M., Vemulapalli, V., Mohseni, M., Wang, P., Stams, T., LaMarche, M. J., Chopra, R., Acker, M. G., & Blacklow, S. C. (2018) · Nature Communications · doi:10.1038/s41467-018-06823-9 · Cited by 167 · see citing works

Combination cancer immunotherapy targeting PD-1 and GITR can rescue CD8 ⁺ T cell dysfunction and maintain memory phenotype

Wang, B., Zhang, W., Jankovic, V., Golubov, J., Poon, P., Oswald, E. M., Gurer, C., Wei, J., Ramos, I., Wu, Q., et al. (2018) · Science Immunology · doi:10.1126/sciimmunol.aat7061 · Cited by 167 · see citing works

Combinations with Allosteric SHP2 Inhibitor TNO155 to Block Receptor Tyrosine Kinase Signaling

Liu, C., Lu, H., Wang, H., Loo, A., Zhang, X., Yang, G., Kowal, C., Delach, S., Wang, Y., Goldoni, S., et al. (2021) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-20-2718 · Cited by 167 · see citing works

The developing story of Sprouty and cancer

Masoumi-Moghaddam, S., Amini, A., & Morris, D. L. (2014) · Cancer and Metastasis Reviews · doi:10.1007/s10555-014-9497-1 · Cited by 155 · see citing works

Shp-2 Is Dispensable for Establishing T Cell Exhaustion and for PD-1 Signaling In Vivo

Rota, G., Niogret, C., Dang, A. T., Barros, C. R., Fonta, N. P., Alfei, F., Morgado, L., Zehn, D., Birchmeier, W., Vivier, E., et al. (2018) · Cell Reports · doi:10.1016/j.celrep.2018.03.026 · Cited by 155 · see citing works

Quantitative Interactomics in Primary T Cells Provides a Rationale for Concomitant PD-1 and BTLA Coinhibitor Blockade in Cancer Immunotherapy

Celis-Gutierrez, J., Blattmann, P., Zhai, Y., Jarmuzynski, N., Ruminski, K., Grégoire, C., Ounoughene, Y., Fiore, F., Aebersold, R., Roncagalli, R., et al. (2019) · Cell Reports · doi:10.1016/j.celrep.2019.05.041 · Cited by 154 · see citing works

Germ-line and somatic PTPN11 mutations in human disease

Tartaglia, M., & Gelb, B. D. (2005) · European Journal of Medical Genetics · doi:10.1016/j.ejmg.2005.03.001 · Cited by 141 · see citing works

Dual Allosteric Inhibition of SHP2 Phosphatase

Fodor, M., Price, E. V., Wang, P., Lu, H., Argintaru, A., Chen, Z., Glick, M., Hao, H.-X., Kato, M., Koenig, R., et al. (2018) · ACS Chemical Biology · doi:10.1021/acschembio.7b00980 · Cited by 133 · see citing works

Mechanism of activating mutations and allosteric drug inhibition of the phosphatase SHP2

Pádua, R. A. P., Sun, Y., Marko, I., Pitsawong, W., Stiller, J. B., Otten, R., & Kern, D. (2018) · Nature Communications · doi:10.1038/s41467-018-06814-w · Cited by 133 · see citing works

PD-1 and BTLA regulate T cell signaling differentially and only partially through SHP1 and SHP2

Xu, X., Hou, B., Fulzele, A., Masubuchi, T., Zhao, Y., Wu, Z., Hu, Y., Jiang, Y., Ma, Y., Wang, H., et al. (2020) · The Journal of Cell Biology · doi:10.1083/jcb.201905085 · Cited by 131 · see citing works

Phosphatases start shedding their stigma of undruggability

Mullard, A. (2018) · Nature Reviews Drug Discovery · doi:10.1038/nrd.2018.201 · Cited by 107 · see citing works

Megakaryocyte-specific deletion of the protein-tyrosine phosphatases Shp1 and Shp2 causes abnormal megakaryocyte development, platelet production, and function

Mazharian, A., Mori, J., Wang, Y., Heising, S., Neel, B. G., Watson, S. P., & Senis, Y. A. (2013) · Blood · doi:10.1182/blood-2012-08-449272 · Cited by 106 · see citing works

Essential role for Ptpn11 in survival of hematopoietic stem and progenitor cells

Chan, G., Cheung, L. S., Yang, W., Milyavsky, M., Sanders, A. D., Gu, S. S., Hong, W. X., Liu, A. X., Wang, X., Barbara, M., et al. (2011) · Blood · doi:10.1182/blood-2010-11-319517 · Cited by 102 · see citing works

Allosteric Inhibition of SHP2 Stimulates Antitumor Immunity by Transforming the Immunosuppressive Environment

Quintana, E., Schulze, C. J., Myers, D. R., Choy, T. J., Mordec, K., Wildes, D. P., Shifrin, N. T., Belwafa, A., Koltun, E. S., Gill, A. L., et al. (2020) · Cancer Research · doi:10.1158/0008-5472.can-19-3038 · Cited by 98 · see citing works

Sticking It to Cancer with Molecular Glue for SHP2

Ran, H., Tsutsumi, R., Araki, T., & Neel, B. G. (2016) · Cancer Cell · doi:10.1016/j.ccell.2016.07.010 · Cited by 93 · see citing works

Optimization of Fused Bicyclic Allosteric SHP2 Inhibitors

Bagdanoff, J. T., Chen, Z., Acker, M., Chen, Y., Chan, H., Dore, M., Firestone, B., Fodor, M., García‐Fortanet, J., Hentemann, M., et al. (2019) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.8b01725 · Cited by 91 · see citing works

SHP2 Inhibition Overcomes RTK-Mediated Pathway Reactivation in KRAS-Mutant Tumors Treated with MEK Inhibitors

Lu, H., Liu, C., Velazquez, R., Wang, H., Dunkl, L. M., Kazic-Legueux, M., Haberkorn, A., Billy, E., Manchado, E., Brachmann, S. M., et al. (2019) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-18-0852 · Cited by 90 · see citing works

Affinity purification mass spectrometry analysis of PD-1 uncovers SAP as a new checkpoint inhibitor

Peled, M., Tocheva, A. S., Sandigursky, S., Nayak, S., Philips, E. A., Nichols, K. E., Strazza, M., Azoulay-Alfaguter, I., Askenazi, M., Neel, B. G., et al. (2018) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1710437115 · Cited by 87 · see citing works

6-Amino-3-methylpyrimidinones as Potent, Selective, and Orally Efficacious SHP2 Inhibitors

Sarver, P., Acker, M., Bagdanoff, J. T., Chen, Z., Chen, Y.-N., Chan, H., Firestone, B., Fodor, M., Fortanet, J., Hao, H., et al. (2019) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.8b01726 · Cited by 87 · see citing works

Selective Inhibitors of the Protein Tyrosine Phosphatase SHP2 Block Cellular Motility and Growth of Cancer Cells in vitro and in vivo

Grosskopf, S., Eckert, C., Arkona, C., Radetzki, S., Böhm, K., Heinemann, U., Wolber, G., von Kries, J. P., Birchmeier, W., & Rademann, J. (2015) · ChemMedChem · doi:10.1002/cmdc.201500015 · Cited by 84 · see citing works

A12 The SHP2 Inhibitor RMC-4630 in Patients with KRAS-Mutant Non-Small Cell Lung Cancer: Preliminary Evaluation of a First-in-Man Phase 1 Clinical Trial

Ou, S. I., Koczywas, M., Ulahannan, S., Janne, P., Pacheco, J., Burris, H., McCoach, C., Wang, J. S., Gordon, M., Haura, E., et al. (2020) · Journal of Thoracic Oncology · doi:10.1016/j.jtho.2019.12.041 · Cited by 73 · see citing works

Structural and Functional Consequences of Three Cancer-Associated Mutations of the Oncogenic Phosphatase SHP2

LaRochelle, J. R., Fodor, M., Xu, X., Durzynska, I., Fan, L., Stams, T., Chan, H. M., LaMarche, M. J., Chopra, R., Wang, P., et al. (2016) · Biochemistry · doi:10.1021/acs.biochem.5b01287 · Cited by 70 · see citing works

Sprouty proteins are in vivo targets of Corkscrew/SHP-2 tyrosine phosphatases

Jarvis, L. A., Peters, S. T., Simon, M. A., Krasnow, M. A., & Smith-Bolton, R. K. (2006) · Development · doi:10.1242/dev.02255 · Cited by 69 · see citing works

Selective inhibition of leukemia-associated SHP2E69K mutant by the allosteric SHP2 inhibitor SHP099

Sun, X., Ren, Y., Gunawan, S., Teng, P., Chen, Z., Lawrence, H., Cai, J., Lawrence, N. J., & Wu, J. (2018) · Leukemia · doi:10.1038/s41375-018-0020-5 · Cited by 69 · see citing works

Structural Insights into the SPRED1-Neurofibromin-KRAS Complex and Disruption of SPRED1-Neurofibromin Interaction by Oncogenic EGFR

Yan, W., Markegard, E., Dharmaiah, S., Urisman, A., Drew, M. R., Esposito, D., Scheffzek, K., Nissley, D. V., McCormick, F. P., & Simanshu, D. K. (2020) · Cell Reports · doi:10.1016/j.celrep.2020.107909 · Cited by 68 · see citing works

Large-Scale Phosphoproteomics Reveals Shp-2 Phosphatase-Dependent Regulators of Pdgf Receptor Signaling

Batth, T. S., Papetti, M., Pfeiffer, A., Tollenaere, M. A. X., Francavilla, C., & Olsen, J. V. (2018) · Cell Reports · doi:10.1016/j.celrep.2018.02.038 · Cited by 65 · see citing works

Functional Redundancy of Sos1 and Sos2 for Lymphopoiesis and Organismal Homeostasis and Survival

Baltanás, F. C., Pérez‐Andrés, M., Ginel-Picardo, A., Díaz, D., Jimeno, D., Liceras-Boillos, P., Kortum, R. L., Samelson, L. E., Órfão, A., & Santos, E. (2013) · Molecular and Cellular Biology · doi:10.1128/mcb.01026-13 · Cited by 60 · see citing works

Off‐target inhibition by active site‐targeting <scp>SHP</scp> 2 inhibitors

Tsutsumi, R., Ran, H., & Neel, B. G. (2018) · FEBS Open Bio · doi:10.1002/2211-5463.12493 · Cited by 54 · see citing works

Activating PTPN11 mutations play a minor role in pediatric and adult solid tumors

Martinelli, S., Carta, C., Flex, E., Binni, F., Cordisco, E. L., Moretti, S., Puxeddu, E., Tonacchera, M., Pinchera, A., McDowell, H. P., et al. (2006) · Cancer Genetics and Cytogenetics · doi:10.1016/j.cancergencyto.2005.10.003 · Cited by 52 · see citing works

Antagonism between binding site affinity and conformational dynamics tunes alternative cis-interactions within Shp2

Sun, J., Lu, S., Ouyang, M., Lin, L.-J., Zhuo, Y., Liu, B., Chien, S., Neel, B. G., & Wang, Y. (2013) · Nature Communications · doi:10.1038/ncomms3037 · Cited by 48 · see citing works

Resistance to allosteric SHP2 inhibition in FGFR-driven cancers through rapid feedback activation of FGFR

Lu, H., Liu, C., Huynh, H. T., Le, T. B. U., LaMarche, M. J., Mohseni, M., Engelman, J. A., Hammerman, P. S., Caponigro, G., & Hao, H.-X. (2020) · Oncotarget · doi:10.18632/oncotarget.27435 · Cited by 45 · see citing works

Gain-of-Function SHP2 E76Q Mutant Rescuing Autoinhibition Mechanism Associated with Juvenile Myelomonocytic Leukemia

Rehman, A. U., Rafiq, H., Rahman, M. U., Li, J., Liu, H., Luo, S., Arshad, T., Wadood, A., & Chen, H.-F. (2019) · Journal of Chemical Information and Modeling · doi:10.1021/acs.jcim.9b00353 · Cited by 40 · see citing works

Sprouty-related Ena/Vasodilator-stimulated Phosphoprotein Homology 1-Domain-containing Protein (SPRED1), a Tyrosine-Protein Phosphatase Non-receptor Type 11 (SHP2) Substrate in the Ras/Extracellular Signal-regulated Kinase (ERK) Pathway

Quintanar‐Audelo, M., Yusoff, P., Sinniah, S., Chandramouli, S., & Guy, G. R. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.212662 · Cited by 33 · see citing works

Dynamic Substrate Enhancement for the Identification of Specific, Second‐Site‐Binding Fragments Targeting a Set of Protein Tyrosine Phosphatases

Schmidt, M. F., Groves, M. R., & Rademann, J. (2011) · ChemBioChem · doi:10.1002/cbic.201100414 · Cited by 30 · see citing works

Mechanistic insights explain the transforming potential of the T507K substitution in the protein-tyrosine phosphatase SHP2

Zhang, R.-Y., Yu, Z.-H., Chen, L., Walls, C. D., Zhang, S., Wu, L., & Zhang, Z.-Y. (2020) · Journal of Biological Chemistry · doi:10.1074/jbc.ra119.010274 · Cited by 22 · see citing works

Can the Help Match the Hype? KRASG12C-Specific Inhibitors and Beyond

Klempner, S. J., & Hata, A. N. (2020) · Cancer Discovery · doi:10.1158/2159-8290.cd-19-1255 · Cited by 15 · see citing works

SH2-Domain-Containing Protein–Tyrosine Phosphatases

Neel, B. G., Gu, H., & Pao, L. I. (2003) · Elsevier eBooks · doi:10.1016/b978-012124546-7/50479-4 · Cited by 4 · see citing works

Abstract 4877: Allosteric inhibition of SHP2 variants containing cancer-associated activating mutations

Wildes, D. P., Aay, N., Buckl, A. K., Hsieh, D., Jogalekar, A. S., Kiss, G., Koltun, E. S., Marquez, A., Mellem, K. T., Romero, J. M., et al. (2018) · Cancer Research · doi:10.1158/1538-7445.am2018-4877 · Cited by 2 · see citing works

Liquid–liquid phase separation drives cellular function and dysfunction in cancer

Mehta, S., & Zhang, J. (2022) · Nature reviews. Cancer · doi:10.1038/s41568-022-00444-7 · Cited by 443 · see citing works

Recent advances in targeting the “undruggable” proteins: from drug discovery to clinical trials

Xie, X., Yu, T., Li, X., Zhang, N., Foster, L. J., Peng, C., Huang, W., & He, G. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01589-z · Cited by 396 · see citing works

Expanding the Reach of Precision Oncology by Drugging All <i>KRAS</i> Mutants

Hofmann, M. H., Gerlach, D., Misale, S., Petronczki, M., & Kraut, N. (2022) · Cancer Discovery · doi:10.1158/2159-8290.cd-21-1331 · Cited by 336 · see citing works

Progress on Ras/MAPK Signaling Research and Targeting in Blood and Solid Cancers

Dillon, M., Lopez, A. R., Lin, E., Sales, D., Perets, R., & Jain, P. (2021) · Cancers · doi:10.3390/cancers13205059 · Cited by 160 · see citing works

Targeting protein phosphatases in cancer immunotherapy and autoimmune disorders

Stanford, S. M., & Bottini, N. (2023) · Nature Reviews Drug Discovery · doi:10.1038/s41573-022-00618-w · Cited by 136 · see citing works

A comprehensive review of SHP2 and its role in cancer

Asmamaw, M. D., Shi, X.-J., Zhang, L.-R., & Liu, H.-M. (2022) · Cellular Oncology · doi:10.1007/s13402-022-00698-1 · Cited by 119 · see citing works

HDAC-targeting epigenetic modulators for cancer immunotherapy

Cheng, B., Pan, W., Xiao, Y., Ding, Z., Zhou, Y., Fei, X., Liu, J., Su, Z., Peng, X., & Chen, J. (2024) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2024.116129 · Cited by 115 · see citing works

Combined Inhibition of SHP2 and CXCR1/2 Promotes Antitumor T-cell Response in NSCLC

Tang, K. H., Li, S., Khodadadi-Jamayran, A., Jen, J., Han, H., Guidry, K., Chen, T., Hao, Y., Fedele, C., Zebala, J. A., et al. (2022) · Cancer Discovery · doi:10.1158/2159-8290.cd-21-0369 · Cited by 105 · see citing works

Genome-Wide CRISPR Screens Identify Multiple Synthetic Lethal Targets That Enhance KRASG12C Inhibitor Efficacy

Mukhopadhyay, S., Huang, H.-Y., Lin, Z., Ranieri, M., Li, S., Sahu, S., Liu, Y., Ban, Y., Guidry, K., Hu, H., et al. (2023) · Cancer Research · doi:10.1158/0008-5472.can-23-2729 · Cited by 105 · see citing works

Targeting KRAS in pancreatic cancer: new drugs on the horizon

Bannoura, S. F., Uddin, M. H., Nagasaka, M., Fazili, F., Hallak, M. N. A., Philip, P. A., El‐Rayes, B. F., & Azmi, A. S. (2021) · Cancer and Metastasis Reviews · doi:10.1007/s10555-021-09990-2 · Cited by 105 · see citing works

Combinatorial strategies to target RAS-driven cancers

Perurena, N., Situ, L., & Cichowski, K. M. (2024) · Nature reviews. Cancer · doi:10.1038/s41568-024-00679-6 · Cited by 104 · see citing works

Endothelial deletion of SHP2 suppresses tumor angiogenesis and promotes vascular normalization

Xu, Z., Guo, C., Ye, Q., Shi, Y., Sun, Y., Zhang, J., Huang, J., Huang, Y., Zeng, C., Zhang, X. Z., et al. (2021) · Nature Communications · doi:10.1038/s41467-021-26697-8 · Cited by 100 · see citing works

Strategies Targeting Protein Tyrosine Phosphatase SHP2 for Cancer Therapy

Song, Y., Wang, S., Zhao, M., Yang, X., & Yu, B. (2022) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.1c02008 · Cited by 100 · see citing works

Drugging the Undruggable: Advances on RAS Targeting in Cancer

Molina‐Arcas, M., Samani, A., & Downward, J. (2021) · Genes · doi:10.3390/genes12060899 · Cited by 73 · see citing works

Along the allostery stream: Recent advances in computational methods for allosteric drug discovery

Ni, D., Chai, Z., Wang, Y., Li, M., Yu, Z., Liu, Y., Lu, S., & Zhang, J. (2021) · Wiley Interdisciplinary Reviews Computational Molecular Science · doi:10.1002/wcms.1585 · Cited by 67 · see citing works

Targeted therapies for KRAS-mutant non-small cell lung cancer: from preclinical studies to clinical development—a narrative review

Santarpia, M., Ciappina, G., Spagnolo, C. C., Squeri, A., Passalacqua, M. I., Aguilar, A., Gonzalez-Cao, M., Giovannetti, E., Silvestris, N., & Rosell, R. (2023) · Translational Lung Cancer Research · doi:10.21037/tlcr-22-639 · Cited by 65 · see citing works

Resistance looms for KRAS G12C inhibitors and rational tackling strategies

Zhang, J., Zhang, J., Liu, Q., Fan, X., Leung, E. L., Yao, X., & Liu, L. (2021) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2021.108050 · Cited by 56 · see citing works

Single-cell transcriptomics reveals opposing roles of Shp2 in Myc-driven liver tumor cells and microenvironment

Chen, W. S., Liang, Y., Zong, M., Liu, J. J., Kaneko, K., Hanley, K. L., Zhang, K., & Feng, G.-S. (2021) · Cell Reports · doi:10.1016/j.celrep.2021.109974 · Cited by 50 · see citing works

Targeting KRAS in Pancreatic Ductal Adenocarcinoma: The Long Road to Cure

de Jesus, V. H. F., Mathias-Machado, M. C., de Farias, J. P. F., Aruquipa, M. P. S., Jacome, A. A. D. A., & Peixoto, R. D. (2023) · Cancers · doi:10.3390/cancers15205015 · Cited by 47 · see citing works

A structural perspective on targeting the RTK /Ras/ MAP kinase pathway in cancer

Heppner, D. E., & Eck, M. J. (2021) · Protein Science · doi:10.1002/pro.4125 · Cited by 37 · see citing works

Epithelial-to-mesenchymal transition hinders interferon-γ-dependent immunosurveillance in lung cancer cells

Tseng, P., Chen, C., Lee, K.-Y., Feng, P., Wang, Y., Satria, R. D., & Lin, C. (2022) · Cancer Letters · doi:10.1016/j.canlet.2022.215712 · Cited by 39 · see citing works

Crystallographic landscape of SHP2 provides molecular insights for SHP2 targeted drug discovery

Song, Y., Yang, X., Wang, S., Zhao, M., & Yu, B. (2022) · Medicinal Research Reviews · doi:10.1002/med.21890 · Cited by 37 · see citing works

A New View of Activating Mutations in Cancer

Nussinov, R., Tsai, C., & Jang, H. (2022) · Cancer Research · doi:10.1158/0008-5472.can-22-2125 · Cited by 35 · see citing works

Small molecule inhibitors for cancer immunotherapy and associated biomarkers – the current status

Schlicher, L., Green, L. G., Romagnani, A., & Renner, F. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1297175 · Cited by 34 · see citing works

Kinetics of RTK activation determine ERK reactivation and resistance to dual BRAF/MEK inhibition in melanoma

Kim, S. S., Carvajal, R. D., Kim, M., & Yang, H. W. (2023) · Cell Reports · doi:10.1016/j.celrep.2023.112570 · Cited by 34 · see citing works

Critical roles of PTPN family members regulated by non-coding RNAs in tumorigenesis and immunotherapy

Tang, X., Qi, C., Zhou, H., & Liu, Y. (2022) · Frontiers in Oncology · doi:10.3389/fonc.2022.972906 · Cited by 33 · see citing works

Identification and validation of a tyrosine metabolism-related prognostic prediction model and characterization of the tumor microenvironment infiltration in hepatocellular carcinoma

Zhou, Y., Li, X., Long, G., Tao, Y., Zhou, L., & Tang, J. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.994259 · Cited by 33 · see citing works

Targeting KRAS in Lung Cancer Beyond KRAS G12C Inhibitors: The Immune Regulatory Role of KRAS and Novel Therapeutic Strategies

Cucurull, M., Notario, L., Sánchez‐Céspedes, M., Hierro, C., Estival, A., Carcereny, E., & Saigí, M. (2022) · Frontiers in Oncology · doi:10.3389/fonc.2021.793121 · Cited by 31 · see citing works

Targeting SHP2 phosphatase in hematological malignancies

Kanumuri, R., Pasupuleti, S. K., Burns, S. S., Ramdas, B., & Kapur, R. (2022) · Expert Opinion on Therapeutic Targets · doi:10.1080/14728222.2022.2066518 · Cited by 31 · see citing works

Structural analysis of the basal state of the Artemis:DNA-PKcs complex

Watanabe, G., Lieber, M. R., & Williams, D. (2022) · Nucleic Acids Research · doi:10.1093/nar/gkac564 · Cited by 32 · see citing works

Targeting KRAS in Non-Small Cell Lung Cancer

de la Fuente, E. C., Olmedo, M. E., Rueda, A. G., Lage, Y., & Garrido, P. (2022) · Frontiers in Oncology · doi:10.3389/fonc.2021.792635 · Cited by 33 · see citing works

Inhibition of SHP2 as an approach to block RAS-driven cancers

Chou, Y., & Bivona, T. G. (2022) · Advances in cancer research · doi:10.1016/bs.acr.2021.07.002 · Cited by 30 · see citing works

Mapping the landscape of genetic dependencies in chordoma

Sharifnia, T., Wawer, M. J., Goodale, A. B., Lee, Y., Kazachkova, M., Dempster, J. M., Muller, S., Levy, J. B., Freed, D. M., Sommer, J., et al. (2023) · Nature Communications · doi:10.1038/s41467-023-37593-8 · Cited by 30 · see citing works

Overcoming Immune Checkpoint Therapy Resistance with SHP2 Inhibition in Cancer and Immune Cells: A Review of the Literature and Novel Combinatorial Approaches

Tojjari, A., Saeed, A., Sadeghipour, A., Kurzrock, R., & Cavalcante, L. L. (2023) · Cancers · doi:10.3390/cancers15225384 · Cited by 30 · see citing works

KRAS-Dependency in Pancreatic Ductal Adenocarcinoma: Mechanisms of Escaping in Resistance to KRAS Inhibitors and Perspectives of Therapy

Gurreri, E., Genovese, G., Perelli, L., Agostini, A., Piro, G., Carbone, C., & Tortora, G. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24119313 · Cited by 27 · see citing works

Precision targeted therapy for EGFR mutation‐positive NSCLC : Dilemmas and coping strategies

Meng, Y., Bai, R., & Cui, J. (2023) · Thoracic Cancer · doi:10.1111/1759-7714.14858 · Cited by 28 · see citing works

SHP2 clinical phenotype, cancer, or RASopathies, can be predicted by mutant conformational propensities

Liu, Y., Zhang, W., Jang, H., & Nussinov, R. (2023) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-023-05052-8 · Cited by 25 · see citing works

Discovery of JAB-3312, a Potent SHP2 Allosteric Inhibitor for Cancer Treatment

Ma, C., Kang, D., Gao, P., Zhang, W., Wu, X.-P., Xu, Z., Han, H., Zhang, L., Cai, Y., Wang, Y., et al. (2024) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.4c00360 · Cited by 25 · see citing works

Oncogenic EML4-ALK assemblies suppress growth factor perception and modulate drug tolerance

Gonzalez-Martinez, D., Roth, L., Mumford, T. R., Guan, J., Le, A., Doebele, R. C., Huang, B., Tulpule, A., Niewiadomska–Bugaj, M., Bivona, T. G., et al. (2024) · Nature Communications · doi:10.1038/s41467-024-53451-7 · Cited by 24 · see citing works

Advances in SHP2 tunnel allosteric inhibitors and bifunctional molecules

Guo, Z., Duan, Y., Sun, K., Zheng, T., Liu, J., Xu, S., & Xu, J. (2024) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2024.116579 · Cited by 25 · see citing works

Targeting Oncogenic KRAS in Non-Small-Cell Lung Cancer

Sunaga, N., Miura, Y., Kasahara, N., & Sakurai, R. (2021) · Cancers · doi:10.3390/cancers13235956 · Cited by 22 · see citing works

Mechanisms, functions and therapeutic targeting of protein tyrosine phosphatases

Tiganis, T., & Tonks, N. K. (2025) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-025-00882-9 · Cited by 22 · see citing works

Discriminating between competing models for the allosteric regulation of oncogenic phosphatase SHP2 by characterizing its active state

Calligari, P. A., Santucci, V., Stella, L., & Bocchinfuso, G. (2021) · Computational and Structural Biotechnology Journal · doi:10.1016/j.csbj.2021.10.041 · Cited by 21 · see citing works

Structure-based design, synthesis and biological evaluation of aminopyrazines as highly potent, selective, and cellularly active allosteric SHP2 inhibitors

Tang, K., Zhao, M., Wu, Y.-H., Wu, Q., Wang, S., Dong, Y., Yu, B., Song, Y., & Liu, H.-M. (2022) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2022.114106 · Cited by 20 · see citing works

Discovery of Orally Bioavailable Purine-Based Inhibitors of the Low-Molecular-Weight Protein Tyrosine Phosphatase

Stanford, S. M., Diaz, M. A., Ardecky, R., Zou, J., Roosild, T. P., Holmes, Z. J., Nguyen, T. P., Hedrick, M. P., Rodiles, S., Guan, A., et al. (2021) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.0c02126 · Cited by 20 · see citing works

Targeting KRAS G12C mutation in lung adenocarcinoma

Rohatgi, A., & Govindan, R. (2021) · Lung Cancer · doi:10.1016/j.lungcan.2021.12.021 · Cited by 17 · see citing works

First Approval of Adagrasib for the Treatment of Non-Small Cell Lung Cancer Harboring a KRASG12C Mutation

De, S. K. (2023) · Current Medicinal Chemistry · doi:10.2174/0929867330666230330122000 · Cited by 15 · see citing works

Off-target autophagy inhibition by SHP2 allosteric inhibitors contributes to their antitumor activity in RAS-driven cancers

Miao, Y., Bai, Y., Miao, J., Murray, A. A., Lin, J., Dong, J., Qu, Z., Zhang, R., Nguyen, Q. D., Wang, S., et al. (2024) · Journal of Clinical Investigation · doi:10.1172/jci177142 · Cited by 16 · see citing works

SHANK3 depletion leads to ERK signalling overdose and cell death in KRAS-mutant cancers

Lilja, J., Kaivola, J., Conway, J. R. W., Vuorio, J., Parkkola, H., Roivas, P., Dibus, M., Chastney, M. R., Varila, T., Jacquemet, G., et al. (2024) · Nature Communications · doi:10.1038/s41467-024-52326-1 · Cited by 14 · see citing works

PI3K inhibition circumvents resistance to SHP2 blockade in metastatic triple-negative breast cancer

Amante, R. J., Jehanno, C., Silva, D. D., Coissieux, M., Ackerknecht, M., Romanet, V., Sethi, A., Hamelin, B., Preca, B., Piscuoglio, S., et al. (2023) · Journal of Mammary Gland Biology and Neoplasia · doi:10.1007/s10911-023-09539-9 · Cited by 15 · see citing works

Structural insights into the pSer/pThr dependent regulation of the SHP2 tyrosine phosphatase in insulin and CD28 signaling

Zeke, A., Takács, T., Sok, P., Németh, K., Kirsch, K., Egri, P., Póti, Á., Bento, I., Tusnády, G., & Reményi, A. (2022) · Nature Communications · doi:10.1038/s41467-022-32918-5 · Cited by 14 · see citing works

Targeting the Interplay of Proteins through PROTACs for the Management of Cancer and Associated Disorders

Kumar, P., Sharma, H., Singh, A., Durgapal, S., Kukreti, G., Bhowmick, M., Bhowmick, P., & Ashique, S. (2024) · Current Cancer Therapy Reviews · doi:10.2174/0115733947304806240417092449 · Cited by 14 · see citing works

Design, Synthesis and Antitumor Activity of a Novel Class of SHP2 Allosteric Inhibitors with a Furanyl Amide-Based Scaffold

Zhu, C., Zhao, H., Yang, W., Chen, K., Liu, X., Yu, Y., Li, R., Tan, R., & Yu, Z. (2024) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.4c01217 · Cited by 14 · see citing works

Allosteric SHP2 inhibition increases apoptotic dependency on BCL2 and synergizes with venetoclax in FLT3- and KIT-mutant AML

Popescu, B. O., Stahlhut, C. E., Tarver, T. C., Wishner, S., Lee, B. J., Peretz, C. A. C., Luck, C., Phojanakong, P. J., Cámara, J. A., Hongo, H., et al. (2023) · Cell Reports Medicine · doi:10.1016/j.xcrm.2023.101290 · Cited by 12 · see citing works

TET3-mediated DNA demethylation modification activates SHP2 expression to promote endometrial cancer progression through the EGFR/ERK pathway

Xue, F., Liu, L., Tao, X., & Zhu, W. (2024) · Journal of Gynecologic Oncology · doi:10.3802/jgo.2024.35.e64 · Cited by 13 · see citing works

Skeletal defects and bone metabolism in Noonan, Costello and cardio-facio-cutaneous syndromes

Papadopoulou, A., & Bountouvi, E. (2023) · Frontiers in Endocrinology · doi:10.3389/fendo.2023.1231828 · Cited by 13 · see citing works

Protein tyrosine phosphatases as emerging targets for cancer immunotherapy

Qu, Z., Dong, J., & Zhang, Z. (2023) · British Journal of Pharmacology · doi:10.1111/bph.16304 · Cited by 12 · see citing works

Direct-to-biology platform: From synthesis to biological evaluation of SHP2 allosteric inhibitors

Ponzi, S., Ferrigno, F., Bisbocci, M., Alli, C., Ontoria, J. M., Petrocchi, A., Toniatti, C., & Torrente, E. (2024) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2024.129626 · Cited by 12 · see citing works

Complex Roles of PTPN11/SHP2 in Carcinogenesis and Prospect of Targeting SHP2 in Cancer Therapy

Scheiter, A., Lu, L., Gao, L. H., & Feng, G. (2023) · Annual Review of Cancer Biology · doi:10.1146/annurev-cancerbio-062722-013740 · Cited by 11 · see citing works

New Directions for Advanced Targeting Strategies of EGFR Signaling in Cancer

Zhou, Y., Takahashi, J., & Sakurai, H. (2024) · Biological and Pharmaceutical Bulletin · doi:10.1248/bpb.b23-00924 · Cited by 11 · see citing works

Protein Tyrosine Phosphatases in Metabolism: A New Frontier for Therapeutics

Bennett, A. M., & Tiganis, T. (2024) · Annual Review of Physiology · doi:10.1146/annurev-physiol-022724-105540 · Cited by 12 · see citing works

Evaluation of KRASG12C inhibitor responses in novel murine KRASG12C lung cancer cell line models

Sisler, D. J., Hinz, T. K., Le, A. T., Kleczko, E. K., Nemenoff, R. A., & Heasley, L. E. (2023) · Frontiers in Oncology · doi:10.3389/fonc.2023.1094123 · Cited by 11 · see citing works

Multi-omics analyses of tumor-associated immune-infiltrating cells with the novel immune checkpoint protein tyrosine phosphatase 1B (PTP1B) in extracellular matrix of brain-lower-grade-glioma (LGG) and uveal-melanoma (UVM)

Bai, K., Zhu, M.-J., Zhang, Y., Li, X., Chen, S., Wang, D., & Dai, Y. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.1053856 · Cited by 10 · see citing works

Clinical variability of neurofibromatosis 1: A modifying role of cooccurring PTPN11 variants and atypical brain MRI findings

D’Amico, A., Rosano, C. L., Pannone, L., Pinna, V., Assunto, A., Motta, M., Ugga, L., Daniele, P., Mandile, R., Mariniello, L., et al. (2021) · Clinical Genetics · doi:10.1111/cge.14040 · Cited by 10 · see citing works

Targeting Protein Tyrosine Phosphatases to Improve Cancer Immunotherapies

Salmond, R. J. (2024) · Cells · doi:10.3390/cells13030231 · Cited by 10 · see citing works

Discovery of novel furanylbenzamide inhibitors that target oncogenic tyrosine phosphatase SHP2 in leukemia cells

Dhanya, R.-P., Finlay, D., Layng, F. I., Lambert, L. J., Celeridad, M., Zhao, M., Barbosa, K., Backer, L. J. S. D., Kwong, E. M., Gosalia, P., et al. (2021) · Journal of Biological Chemistry · doi:10.1016/j.jbc.2021.101477 · Cited by 10 · see citing works

Role of Epiregulin in Lung Tumorigenesis and Therapeutic Resistance

Sunaga, N., Miura, Y., Masuda, T., & Sakurai, R. (2024) · Cancers · doi:10.3390/cancers16040710 · Cited by 9 · see citing works

Research progress in bifunctional small molecules for cancer immunotherapy

Cheng, B., Li, H., Hong, Y., Zhou, Y., Chen, J., Shao, C., & Kong, Z. (2025) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2025.117289 · Cited by 9 · see citing works

Proteolysis-Targeting Chimera Molecules Targeting SHP2

Yu, D., Zheng, M., Liu, Y., Chen, L., & Li, H. (2022) · Future Medicinal Chemistry · doi:10.4155/fmc-2021-0324 · Cited by 9 · see citing works

Adagrasib: a novel inhibitor for KRAS G12C -mutated non-small-cell lung cancer

Guo, M. Z., Marrone, K. A., Spira, A. I., & Rosner, S. (2023) · Future Oncology · doi:10.2217/fon-2022-1106 · Cited by 9 · see citing works

Setting sail: Maneuvering SHP2 activity and its effects in cancer

Welsh, C. L., Allen, S., & Madan, L. K. (2023) · Advances in cancer research · doi:10.1016/bs.acr.2023.03.003 · Cited by 8 · see citing works

Waking immune-resistant tumors with neddylation

Huntoon, K. M., Jiang, W., & Kim, B. Y. S. (2023) · Journal of Clinical Investigation · doi:10.1172/jci167894 · Cited by 8 · see citing works

Targeting KRAS in colorectal cancer (Review)

Zhang, M., Wu, D., Tang, C. Y. L., Zhang, L., Zhang, S., Li, W., Li, N., & Yan, X. (2025) · Molecular and Clinical Oncology · doi:10.3892/mco.2025.2873 · Cited by 7 · see citing works

Ajuforrestin A, an Abietane Diterpenoid from Ajuga ovalifolia var. calanthe, Induces A549 Cell Apoptosis by Targeting SHP2

Yan, H.-L., Jiang, M., Yang, F., Tang, X., Lin, M., Zhou, C., Tan, Y., & Liu, D. (2022) · Molecules · doi:10.3390/molecules27175469 · Cited by 7 · see citing works

Clinical Progress of KRAS-targeted Therapies: What next?

Nagasaka, M., & Azmi, A. S. (2022) · Future Medicinal Chemistry · doi:10.4155/fmc-2022-0128 · Cited by 7 · see citing works

Promising natural products targeting protein tyrosine phosphatase SHP2 for cancer therapy

Lu, J., Yu, D., Li, H., Qin, P., Chen, H., & Chen, L. (2024) · Phytotherapy Research · doi:10.1002/ptr.8185 · Cited by 6 · see citing works

SHP2 Inhibitors Show Anti-Myeloma Activity and Synergize With Bortezomib in the Treatment of Multiple Myeloma

Zhou, P., Xiao, M., Li, W., Sun, X., Bai, Y., Meng, F., Zhu, Z., Yuan, W., & Sun, K. (2022) · Frontiers in Pharmacology · doi:10.3389/fphar.2022.841308 · Cited by 6 · see citing works

Shp2 in Alveolar Macrophages Regulates Macrophage I Phenotype in Acute Lung Injury

Wang, D., & Cao, Q. (2022) · International Journal of Toxicology · doi:10.1177/10915818221105227 · Cited by 6 · see citing works

SHP2 inhibition displays efficacy as a monotherapy and in combination with JAK2 inhibition in preclinical models of myeloproliferative neoplasms

Pandey, G., Mazzacurati, L., Rowsell, T. M., Horvat, N. P., Amin, N. E., Zhang, G., Akuffo, A. A., Colin, C., Haura, E. B., Kuykendall, A. T., et al. (2024) · American Journal of Hematology · doi:10.1002/ajh.27282 · Cited by 6 · see citing works

Cross the Undruggable Barrier, the Development of SHP2 Inhibitors: From Catalytic Site Inhibitors to Allosteric Inhibitors

Guo, Y. L., Xu, Y., Dong, X., & Zhang, J. (2021) · ChemistrySelect · doi:10.1002/slct.202100186 · Cited by 5 · see citing works

Targeting SHP2 with Natural Products: Exploring Saponin-Based Allosteric Inhibitors and Their Therapeutic Potential

Moon, D. (2025) · Current Issues in Molecular Biology · doi:10.3390/cimb47050309 · Cited by 4 · see citing works

SHP2 is a multifunctional target in anaplastic thyroid carcinoma: Cell intrinsic and immune-dependent anti-tumor effects

Marotta, M., Zirpoli, S., Prevete, N., Simone, C. D., Cristofano, A. D., Liotti, F., & Melillo, R. M. (2025) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2025.118384 · Cited by 4 · see citing works

From Stem to Sternum: The Role of Shp2 in the Skeleton

Jensen, N. R., Kelly, R. R., Kelly, K. D., Khoo, S. K., Sidles, S. J., & LaRue, A. C. (2022) · Calcified Tissue International · doi:10.1007/s00223-022-01042-3 · Cited by 4 · see citing works

Causal associations of BAFF-R on IgD+ CD24- B cell immune cell trait with hepatocellular carcinoma and the mediating role of phenylacetylglutamate levels: a Mendelian randomization study

Zhu, X., Qiu, Z., Yang, M., Yang, J., Kong, L., Li, L., Huang, Y., & Xie, L. (2024) · Journal of Cancer · doi:10.7150/jca.96059 · Cited by 4 · see citing works

A hotspot phosphorylation site on SHP2 drives oncoprotein activation and drug resistance

Karunaraj, P., Scheele, R., Wells, M. L., Rathod, R., Gokulu, I. S., Abrahamson, S. R., Taylor, L., Chowdhury, L., Kazmi, A., Song, W., et al. (2026) · Nature Communications · doi:10.1038/s41467-026-70060-8 · Cited by 7 · see citing works

Enzyme Is the Name—Adapter Is the Game

Huber, M., & Brummer, T. (2024) · Cells · doi:10.3390/cells13151249 · Cited by 3 · see citing works

A first-in-human phase 1 study of the SHP2 inhibitor BBP-398 in patients with advanced solid tumors

Falchook, G. S., Xavier, C. B., Veenhuyzen, D. F. V., Malhotra, J. D., Sadeghi, S., Kalebasty, A. R., Wood, L., Rahman, F., Li, E., Pak, Y., et al. (2026) · npj Precision Oncology · doi:10.1038/s41698-026-01340-1 · Cited by 3 · see citing works

Systematic and precise interventions for KRAS-mutant cancers

Liang, J., Wu, J., Zhang, Y., Wang, H., Zheng, Y., & He, Q. (2026) · Experimental Hematology and Oncology · doi:10.1186/s40164-026-00763-7 · Cited by 3 · see citing works

Study on SHP2 Conformational Transition and Structural Characterization of Its High-Potency Allosteric Inhibitors by Molecular Dynamics Simulations Combined with Machine Learning

Wujieti, B., Hao, M., Liu, E., Zhou, L., Wang, H., Zhang, Y., Cui, W., & Chen, B. (2024) · Molecules · doi:10.3390/molecules30010014 · Cited by 3 · see citing works

Integration of signaling pathway and bromodomain and extra-terminal domain inhibition for the treatment of mutant Kirsten rat sarcoma viral oncogene homolog cancer

Hamilton, G., Stickler, S., & Rath, B. (2023) · Exploration of Targeted Anti-tumor Therapy · doi:10.37349/etat.2023.00178 · Cited by 3 · see citing works

Therapeutic Targeting of RAS Mutant Cancers

Stites, E. C., Paskvan, K. V., & Kato, S. (2022) · Cambridge University Press eBooks · doi:10.1017/9781009064828 · Cited by 2 · see citing works

Structure-Guided Design of Pyrazolopyrimidinones as Highly Potent and Selective Allosteric SHP2 Inhibitors

Song, Y., Ren, X., Yang, X., Xiong, J., Wang, W., Tang, K., & Yu, B. (2025) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.5c00524 · Cited by 2 · see citing works

Exploring the allosteric effect of SHP2 Tyr62 phosphorylation on the emergence of acquired resistance to allosteric inhibitor SHP099

Du, T., Gu, L., Xu, S., Zhang, J., Qiu, X., Liu, W., Zheng, G., Li, B., Zhou, B., & Li, M.-Y. (2025) · Journal of Biomolecular Structure and Dynamics · doi:10.1080/07391102.2025.2507815 · Cited by 2 · see citing works

SHP2-targeted cancer therapeutics: Structural insights, inhibitor development and emerging modalities

Zhang, Y., Zhu, C., Si, C., Lin, Y., Guo, Q., Zhou, H., & Yu, Z. (2026) · Bioorganic & Medicinal Chemistry · doi:10.1016/j.bmc.2026.118708 · Cited by 2 · see citing works

SHP2 is involved in the occurrence, development and prognosis of cancer

Li, S., Qu, J., Wang, X., Zou, Q., & Li, C. (2023) · Oncology Letters · doi:10.3892/ol.2023.13979 · Cited by 2 · see citing works

Sidestepping SHP2 inhibition

Popescu, B. O., & Shannon, K. (2023) · The Journal of Experimental Medicine · doi:10.1084/jem.20230082 · Cited by 2 · see citing works

Prediction of SHP2-E76K binding sites based on molecular dynamics simulation and Markov algorithm

Zhang, S., Chen, L., Shi, Z., Li, X., & Ma, Y. (2024) · Journal of Biomolecular Structure and Dynamics · doi:10.1080/07391102.2024.2431193 · Cited by 1 · see citing works

Structure-guided expansion strategy unveils potent allosteric SHP2 inhibitors with synergistic efficacy against AML through MCL-1 co-targeting

Zhang, M., Wu, S., Liu, M., Li, H., Wang, L., Duan, F., Han, R., Shan, C., Jiang, Z., Liao, J., et al. (2025) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2025.117988 · Cited by 1 · see citing works

PZR: Advances in research from cellular signaling Hub to emerging therapeutic targets

Wang, H. P., Sha, W., Fu, Y., & Wang, H. (2025) · Cellular Signalling · doi:10.1016/j.cellsig.2025.112061 · Cited by 1 · see citing works

Tumoral IL-10-activated SHP2 in macrophages promotes mammary carcinoma progression

Gao, J., Chen, Z., Wang, Y., Guo, L., Fan, M., Zhou, L., Wang, L., Huang, Y., Sun, Y., Guo, W., et al. (2024) · Fundamental Research · doi:10.1016/j.fmre.2024.03.026 · Cited by 1 · see citing works

Overcoming Immune Checkpoint Therapy Resistance with SHP2 Inhibition in Cancer and Immune Cells: A Review of the Literature and Novel Combinatorial Approaches

Tojjari, A., Saeed, A., Sadeghipour, A., Kurzrock, R., & Cavalcante, L. L. (2023) · Cancers · doi:10.3390/cancers15225384 · Cited by 30 · see citing works

Inhibition of SHP2 as an approach to block RAS-driven cancers

Chou, Y., & Bivona, T. G. (2022) · Advances in cancer research · doi:10.1016/bs.acr.2021.07.002 · Cited by 30 · see citing works

Strategies to overcome drug resistance using SHP2 inhibitors

Liu, M., Gao, S., Elhassan, R. M., Hou, X., & Fang, H. (2021) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2021.03.037 · Cited by 59 · see citing works

Allosteric Inhibitors of SHP2 with Therapeutic Potential for Cancer Treatment

Xie, J., Si, X., Gu, S., Wang, M., Shen, J. H., Li, H., Shen, J. H., Li, D., Fang, Y., Liu, C., et al. (2017) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.7b01520 · Cited by 113 · see citing works

Research progress in development of SHP2 inhibitors and their application in tumor therapy

Yuxiao, S., Xiaoguang, L., & Ba, Q. (2026) · DOAJ (DOAJ: Directory of Open Access Journals) · doi:10.3969/j.issn.1674-8115.2026.06.003