Enhancing Antiproliferative Activity and Selectivity of a FLT-3 Inhibitor by Proteolysis Targeting Chimera Conversion

Cell Signaling by Receptor Tyrosine Kinases

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Protacs: Chimeric molecules that target proteins to the Skp1–Cullin–F box complex for ubiquitination and degradation

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Phthalimide conjugation as a strategy for in vivo target protein degradation

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Analysis of FLT3-activating mutations in 979 patients with acute myelogenous leukemia: association with FAB subtypes and identification of subgroups with poor prognosis

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Induced protein degradation: an emerging drug discovery paradigm

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Catalytic in vivo protein knockdown by small-molecule PROTACs

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Selective Small Molecule Induced Degradation of the BET Bromodomain Protein BRD4

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Lessons in PROTAC Design from Selective Degradation with a Promiscuous Warhead

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SU11248 is a novel FLT3 tyrosine kinase inhibitor with potent activity in vitro and in vivo

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Validation of ITD mutations in FLT3 as a therapeutic target in human acute myeloid leukaemia

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The Advantages of Targeted Protein Degradation Over Inhibition: An RTK Case Study

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Acute myeloid leukemia: Epidemiology and etiology

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AC220 is a uniquely potent and selective inhibitor of FLT3 for the treatment of acute myeloid leukemia (AML)

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Modular PROTAC design for the degradation of oncogenic BCR-ABL

Lai, A. C., Toure, M., Hellerschmied, D., Salami, J., Jaime‐Figueroa, S., Ko, E., Hines, J., & Crews, C. M. (2016) · Angewandte Chemie International Edition · doi:10.1002/anie.201507634 · Cited by 618 · see citing works

Targeting the von Hippel-Lindau E3 ubiquitin ligase using small molecules to disrupt the VHL/HIF-1α interaction

Buckley, D. L., Van Molle, I., Gareiss, P. C., Tae, H. S., Michel, J., Noblin, D. J., Jorgensen, W. L., Ciulli, A., & Crews, C. M. (2012) · Journal of the American Chemical Society · doi:10.1021/ja209924v · Cited by 569 · see citing works

Chemical Genetic Control of Protein Levels: Selective in Vivo Targeted Degradation

Schneekloth, J. S., Fonseca, F. N., Koldobskiy, M. A., Mandal, A., Deshaies, R. J., Sakamoto, K. M., & Crews, C. M. (2004) · Journal of the American Chemical Society · doi:10.1021/ja039025z · Cited by 502 · see citing works

HaloPROTACS: Use of Small Molecule PROTACs to Induce Degradation of HaloTag Fusion Proteins

Buckley, D. L., Raina, K., Darricarrere, N., Hines, J., Gustafson, J. L., Smith, I. E., Miah, A. H., Harling, J. D., & Crews, C. M. (2015) · ACS Chemical Biology · doi:10.1021/acschembio.5b00442 · Cited by 488 · see citing works

A Chemoproteomic Approach to Query the Degradable Kinome Using a Multi-kinase Degrader

Huang, H.-T., Dobrovolsky, D., Paulk, J., Yang, G., Weisberg, E. L., Doctor, Z. M., Buckley, D. L., Cho, J.-H., Ko, E., Jang, J., et al. (2018) · Cell Chemical Biology · doi:10.1016/j.chembiol.2017.10.005 · Cited by 437 · see citing works

Protein Knockdown Using Methyl Bestatin−Ligand Hybrid Molecules: Design and Synthesis of Inducers of Ubiquitination-Mediated Degradation of Cellular Retinoic Acid-Binding Proteins

Itoh, Y., Ishikawa, M., Naito, M., & Hashimoto, Y. (2010) · Journal of the American Chemical Society · doi:10.1021/ja100691p · Cited by 404 · see citing works

Targeting the C481S ibrutinib-resistance mutation in Bruton’s tyrosine kinase using PROTAC-mediated degradation

Buhimschi, A. D., Armstrong, H. A., Toure, M., Jaime-Figueroa, S., Chen, T. L., Lehman, A. M., Woyach, J. A., Johnson, A. J., Byrd, J. C., & Crews, C. M. (2018) · Biochemistry · doi:10.1021/acs.biochem.8b00391 · Cited by 394 · see citing works

Androgen receptor degradation by the proteolysis-targeting chimera ARCC-4 outperforms enzalutamide in cellular models of prostate cancer drug resistance

Salami, J., Alabi, S., Willard, R. R., Vitale, N. J., Wang, J., Dong, H., Jin, M., McDonnell, D. P., Crew, A. P., Neklesa, T. K., et al. (2018) · Communications Biology · doi:10.1038/s42003-018-0105-8 · Cited by 349 · see citing works

Small‐Molecule Inhibitors of the Interaction between the E3 Ligase VHL and HIF1α

Buckley, D. L., Gustafson, J. L., Van Molle, I., Roth, A. G., Tae, H. S., Gareiss, P. C., Jorgensen, W. L., Ciulli, A., & Crews, C. M. (2012) · Angewandte Chemie International Edition · doi:10.1002/anie.201206231 · Cited by 302 · see citing works

Waste disposal—An attractive strategy for cancer therapy

Salami, J., & Crews, C. M. (2017) · Science · doi:10.1126/science.aam7340 · Cited by 279 · see citing works

Chemically Induced Degradation of Sirtuin 2 (Sirt2) by a Proteolysis Targeting Chimera (PROTAC) Based on Sirtuin Rearranging Ligands (SirReals)

Schiedel, M., Herp, D., Hammelmann, S., Swyter, S., Lehotzky, A., Robaa, D., Oláh, J., Ovádi, J., Sippl, W., & Jung, M. (2017) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.6b01872 · Cited by 275 · see citing works

Small-Molecule Modulation of Protein Homeostasis.

Burslem, G., & Crews, C. (2017) · Chemical Reviews · doi:10.1021/acs.chemrev.7b00077 · Cited by 256 · see citing works

Proteolysis-Targeting Chimeras: Induced Protein Degradation as a Therapeutic Strategy

Ottis, P., & Crews, C. M. (2017) · ACS Chemical Biology · doi:10.1021/acschembio.6b01068 · Cited by 227 · see citing works

Expression of the FMS/KIT-like gene FLT3 in human acute leukemias of the myeloid and lymphoid lineages

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Identification of N-(5-tert-Butyl-isoxazol-3-yl)-N′-{4-[7-(2-morpholin-4-yl-ethoxy)imidazo[2,1-b][1,3]benzothiazol-2-yl]phenyl}urea Dihydrochloride (AC220), a Uniquely Potent, Selective, and Efficacious FMS-Like Tyrosine Kinase-3 (FLT3) Inhibitor

Chao, Q., Sprankle, K. G., Grotzfeld, R. M., Lai, A. G., Carter, T. A., Velasco, A. M., Gunawardane, R. N., Cramer, M. D., Gardner, M. F., James, J., et al. (2009) · Journal of Medicinal Chemistry · doi:10.1021/jm9007533 · Cited by 211 · see citing works

Small‐Molecule‐Mediated Degradation of the Androgen Receptor through Hydrophobic Tagging

Gustafson, J. L., Neklesa, T. K., Cox, C. S., Roth, A. G., Buckley, D. L., Tae, H. S., Sundberg, T. B., Stagg, D. B., Hines, J., McDonnell, D. P., et al. (2015) · Angewandte Chemie International Edition · doi:10.1002/anie.201503720 · Cited by 206 · see citing works

A pharmacodynamic study of the FLT3 inhibitor KW-2449 yields insight into the basis for clinical response

Pratz, K. W., Cortes, J. E., Roboz, G. J., Rao, N. S., Arowojolu, O. A., Stine, A., Shiotsu, Y., Shudo, A., Akinaga, S., Small, D., et al. (2008) · Blood · doi:10.1182/blood-2008-09-177030 · Cited by 181 · see citing works

Antitumor activity of sorafenib in FLT3-driven leukemic cells

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FLT3 inhibitors for acute myeloid leukemia: a review of their efficacy and mechanisms of resistance

Grunwald, M. R., & Levis, M. J. (2013) · International Journal of Hematology · doi:10.1007/s12185-013-1334-8 · Cited by 153 · see citing works

Chemical approaches to targeted protein degradation through modulation of the ubiquitin–proteasome pathway

Collins, I., Wang, H., Caldwell, J., & Chopra, R. (2017) · Biochemical Journal · doi:10.1042/bcj20160762 · Cited by 135 · see citing works

Activity of ponatinib against clinically-relevant AC220-resistant kinase domain mutants of FLT3-ITD

Smith, C. C., Lasater, E. A., Zhu, X., Lin, K. C., Stewart, W. K., Damon, L. E., Salerno, S. N., & Shah, N. P. (2013) · Blood · doi:10.1182/blood-2012-07-442871 · Cited by 130 · see citing works

Cancer cell death induced by novel small molecules degrading the TACC3 protein via the ubiquitin–proteasome pathway

Ohoka, N., Nagai, K., Hattori, T., Okuhira, K., Shibata, N., Cho, N. J., & Naito, M. (2014) · Cell Death and Disease · doi:10.1038/cddis.2014.471 · Cited by 100 · see citing works

Pim kinases modulate resistance to FLT3 tyrosine kinase inhibitors in FLT3-ITD acute myeloid leukemia

Green, A. S., Maciel, T. T., Yin, C., Mazed, F., Townsend, E. C., Pilorge, S., Lambert, M., Paubelle, É., Jacquel, A., Zylbersztejn, F., et al. (2015) · Science Advances · doi:10.1126/sciadv.1500221 · Cited by 96 · see citing works

Proteolysis-Targeting Chimeras: Harnessing the Ubiquitin-Proteasome System to Induce Degradation of Specific Target Proteins

Coleman, K. G., & Crews, C. M. (2017) · Annual Review of Cancer Biology · doi:10.1146/annurev-cancerbio-030617-050430 · Cited by 66 · see citing works

Breakdown of the FLT3-ITD/STAT5 Axis and Synergistic Apoptosis Induction by the Histone Deacetylase Inhibitor Panobinostat and FLT3-Specific Inhibitors

Pietschmann, K., Bolck, H. A., Buchwald, M., Spielberg, S., Polzer, H., Spiekermann, K., Bug, G., Heinzel, T., Böhmer, F.-D., & Krämer, O. H. (2012) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-12-0129 · Cited by 50 · see citing works

Reversible Resistance Induced by FLT3 Inhibition: A Novel Resistance Mechanism in Mutant FLT3-Expressing Cells

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Development of a Small Hybrid Molecule That Mediates Degradation of His-Tag Fused Proteins

Okitsu, K., Hattori, T., Misawa, T., Shoda, T., Kurihara, M., Naito, M., & Demizu, Y. (2017) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.7b00413 · Cited by 28 · see citing works

Proteolysis-Targeting Chimeras as Therapeutics and Tools for Biological Discovery

Burslem, G. M., & Crews, C. M. (2020) · Cell · doi:10.1016/j.cell.2019.11.031 · Cited by 1,079 · see citing works

PROteolysis TArgeting Chimeras (PROTACs) — Past, present and future

Pettersson, M., & Crews, C. M. (2019) · Drug Discovery Today Technologies · doi:10.1016/j.ddtec.2019.01.002 · Cited by 818 · see citing works

Advancing targeted protein degradation for cancer therapy

Dale, B., Cheng, M., Park, K., Kanıskan, H. Ü., Xiong, Y., & Jin, J. J. (2021) · Nature reviews. Cancer · doi:10.1038/s41568-021-00365-x · Cited by 671 · see citing works

A Potent and Selective Small-Molecule Degrader of STAT3 Achieves Complete Tumor Regression In Vivo

Bai, L., Zhou, H., Xu, R., Zhao, Y., Chinnaswamy, K., McEachern, D., Chen, J., Yang, C.-Y., Liu, Z., Wang, M., et al. (2019) · Cancer Cell · doi:10.1016/j.ccell.2019.10.002 · Cited by 652 · see citing works

PROTACs: great opportunities for academia and industry

Sun, X., Gao, H., Yang, Y., He, M., Wu, Y., Song, Y.-G., Tong, Y., & Rao, Y. (2019) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-019-0101-6 · Cited by 651 · see citing works

Targeted protein degradation: elements of PROTAC design

Paiva, S.-L., & Crews, C. M. (2019) · Current Opinion in Chemical Biology · doi:10.1016/j.cbpa.2019.02.022 · Cited by 586 · see citing works

Proteolysis-targeting chimera (PROTAC) for targeted protein degradation and cancer therapy

Li, X., & Song, Y. (2020) · Journal of Hematology & Oncology · doi:10.1186/s13045-020-00885-3 · Cited by 550 · see citing works

PROTACs: An Emerging Therapeutic Modality in Precision Medicine

Nalawansha, D. A., & Crews, C. M. (2020) · Cell chemical biology · doi:10.1016/j.chembiol.2020.07.020 · Cited by 514 · see citing works

Targeted Degradation of Oncogenic KRAS ^G12C by VHL-Recruiting PROTACs

Bond, M. J., Chu, L., Nalawansha, D. A., Li, K., & Crews, C. M. (2020) · ACS Central Science · doi:10.1021/acscentsci.0c00411 · Cited by 450 · see citing works

Proteolysis-targeting chimeras (PROTACs) in cancer therapy

Li, X., Pu, W., Zheng, Q., Ai, M., Chen, S., & Peng, Y. (2022) · Molecular Cancer · doi:10.1186/s12943-021-01434-3 · Cited by 374 · see citing works

An overview of PROTACs: a promising drug discovery paradigm

Zi, L., Hu, M., Yu, Y., Du, C., Zhou, H., Liu, C., Chen, Y., Fan, L., Ma, H., Gong, Y., et al. (2022) · Molecular Biomedicine · doi:10.1186/s43556-022-00112-0 · Cited by 366 · see citing works

Antibody–PROTAC Conjugates Enable HER2-Dependent Targeted Protein Degradation of BRD4

Maneiro, M., Forte, N., Shchepinova, M. M., Kounde, C. S., Chudasama, V., Baker, J. R., & Tate, E. W. (2020) · ACS Chemical Biology · doi:10.1021/acschembio.0c00285 · Cited by 350 · see citing works

Targeted protein degradation: advances in drug discovery and clinical practice

Zhong, G., Chang, X., Xie, W., & Zhou, X. (2024) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-024-02004-x · Cited by 326 · see citing works

Degradation of proteins by PROTACs and other strategies

Wang, Y., Jiang, X., Feng, F., Liu, W., & Sun, H. (2020) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2019.08.001 · Cited by 335 · see citing works

Targeted protein degradation: A promise for undruggable proteins

Samarasinghe, K. T. G., & Crews, C. M. (2021) · Cell chemical biology · doi:10.1016/j.chembiol.2021.04.011 · Cited by 291 · see citing works

Major advances in targeted protein degradation: PROTACs, LYTACs, and MADTACs

Alabi, S. B., & Crews, C. M. (2021) · Journal of Biological Chemistry · doi:10.1016/j.jbc.2021.100647 · Cited by 271 · see citing works

Proteolysis targeting chimera (PROTAC) in drug discovery paradigm: Recent progress and future challenges

Zeng, S., Huang, W., Zheng, X., Cheng, L., Zhang, Z., Wang, J., & Shen, Z. (2020) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2020.112981 · Cited by 262 · see citing works

PROteolysis TArgeting Chimeras (PROTACs) as emerging anticancer therapeutics

Khan, S., He, Y., Zhang, X., Yuan, Y., Pu, S., Kong, Q., Zheng, G., & Zhou, D. (2020) · Oncogene · doi:10.1038/s41388-020-1336-y · Cited by 252 · see citing works

Discovery of Highly Potent and Efficient PROTAC Degraders of Androgen Receptor (AR) by Employing Weak Binding Affinity VHL E3 Ligase Ligands

Han, X., Zhao, L., Xiang, W., Qin, C., Miao, B., Xu, T., Wang, M., Yang, C., Chinnaswamy, K., Stuckey, J. A., et al. (2019) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.9b01393 · Cited by 229 · see citing works

Targeting BCR-ABL1 in Chronic Myeloid Leukemia by PROTAC-Mediated Targeted Protein Degradation

Burslem, G. M., Schultz, A. R., Bondeson, D. P., Eide, C. A., Savage Stevens, S. L., Druker, B. J., & Crews, C. M. (2019) · Cancer Research · doi:10.1158/0008-5472.can-19-1236 · Cited by 212 · see citing works

Recent Developments in PROTAC‐Mediated Protein Degradation: From Bench to Clinic

Hu, Z., & Crews, C. M. (2022) · ChemBioChem · doi:10.1002/cbic.202100270 · Cited by 231 · see citing works

Receptor tyrosine kinases and cancer: oncogenic mechanisms and therapeutic approaches

Saraon, P., Pathmanathan, S., Snider, J. D., Lyakisheva, A., Wong, V., & Štagljar, I. (2021) · Oncogene · doi:10.1038/s41388-021-01841-2 · Cited by 212 · see citing works

Targeted protein degradation as a powerful research tool in basic biology and drug target discovery

Wu, T., Yoon, H., Xiong, Y., Dixon-Clarke, S. E., Nowak, R. P., & Fischer, E. S. (2020) · Nature Structural & Molecular Biology · doi:10.1038/s41594-020-0438-0 · Cited by 188 · see citing works

Phenyl‐Glutarimides: Alternative Cereblon Binders for the Design of PROTACs

Min, J., Mayasundari, A., Keramatnia, F., Jonchère, B., Yang, S. W., Jarusiewicz, J., Actis, M., Das, S., Young, B. M., Slavish, J., et al. (2021) · Angewandte Chemie International Edition · doi:10.1002/anie.202108848 · Cited by 182 · see citing works

Harnessing the Power of Proteolysis for Targeted Protein Inactivation

Verma, R., Mohl, D., & Deshaies, R. J. (2020) · Molecular Cell · doi:10.1016/j.molcel.2020.01.010 · Cited by 185 · see citing works

Targeted degradation of transcription factors by TRAFTACs: TRAnscription Factor TArgeting Chimeras

Samarasinghe, K. T. G., Jaime-Figueroa, S., Burgess, M., Nalawansha, D. A., Dai, K., Hu, Z., Bebenek, A., Holley, S. A., & Crews, C. M. (2021) · Cell Chemical Biology · doi:10.1016/j.chembiol.2021.03.011 · Cited by 182 · 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

Cereblon versus VHL: Hijacking E3 ligases against each other using PROTACs

Girardini, M., Maniaci, C., Hughes, S. J., Testa, A., & Ciulli, A. (2019) · Bioorganic & Medicinal Chemistry · doi:10.1016/j.bmc.2019.02.048 · Cited by 157 · see citing works

Rationalizing PROTAC-Mediated Ternary Complex Formation Using Rosetta

Bai, N., Miller, S. A., Andrianov, G. V., Yates, M., Kirubakaran, P., & Karanicolas, J. (2021) · Journal of Chemical Information and Modeling · doi:10.1021/acs.jcim.0c01451 · Cited by 157 · see citing works

Characteristic roadmap of linker governs the rational design of PROTACs

Dong, Y., Ma, T., Xu, T., Feng, Z., Li, Y., Song, L., Yao, X., Ashby, C. R., & Hao, G.-F. (2024) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2024.04.007 · Cited by 146 · see citing works

Strategies toward Discovery of Potent and Orally Bioavailable Proteolysis Targeting Chimera Degraders of Androgen Receptor for the Treatment of Prostate Cancer

Han, X., Zhao, L., Xiang, W., Qin, C., Miao, B., McEachern, D., Wang, Y., Metwally, H., Wang, L., Matvekas, A., et al. (2021) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.1c00882 · Cited by 170 · see citing works

Discovery of SIAIS178 as an Effective BCR-ABL Degrader by Recruiting Von Hippel–Lindau (VHL) E3 Ubiquitin Ligase

Zhao, Q., Ren, C., Liu, L., Chen, J., Shao, Y., Sun, N., Sun, R., Kong, Y., Ding, X., Zhang, X., et al. (2019) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.9b01264 · Cited by 134 · see citing works

Proteolysis targeting chimeras (PROTACs) are emerging therapeutics for hematologic malignancies

He, Y., Khan, S., Huo, Z., Lv, D., Zhang, X., Liu, X., Yuan, Y., Hromas, R., Xu, M., Zheng, G., et al. (2020) · Journal of Hematology & Oncology · doi:10.1186/s13045-020-00924-z · Cited by 126 · see citing works

Strategies for designing proteolysis targeting chimaeras (PROTACs)

He, S., Dong, G., Cheng, J., Wu, Y., & Sheng, C. (2022) · Medicinal Research Reviews · doi:10.1002/med.21877 · Cited by 118 · see citing works

Development of Small Molecule Chimeras That Recruit AhR E3 Ligase to Target Proteins

Ohoka, N., Tsuji, G., Shoda, T., Fujisato, T., Kurihara, M., Demizu, Y., & Naito, M. (2019) · ACS Chemical Biology · doi:10.1021/acschembio.9b00704 · Cited by 118 · see citing works

Discovery of selective CDK9 degraders with enhancing antiproliferative activity through PROTAC conversion

Qiu, X., Li, Y., Yu, B., Ren, J., Huang, H., Wang, M., Ding, H., Li, Z., Wang, J., & Bian, J. (2020) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2020.113091 · Cited by 117 · see citing works

PROTAC’ing oncoproteins: targeted protein degradation for cancer therapy

Kelm, J. M., Pandey, D. S., Malin, E., Kansou, H. W., Arora, S., Kumar, R., & Gavande, N. S. (2023) · Molecular Cancer · doi:10.1186/s12943-022-01707-5 · Cited by 115 · see citing works

Annual review of PROTAC degraders as anticancer agents in 2022

Wang, X., Qin, Z.-L., Li, N., Jia, M.-Q., Liu, Q.-G., Bai, Y., Song, J., Yuan, S., & Zhang, S. (2024) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2024.116166 · Cited by 107 · see citing works

First orally bioavailable prodrug of proteolysis targeting chimera (PROTAC) degrades cyclin-dependent kinases 2/4/6 in vivo

Wei, M., Zhao, R., Cao, Y., Wei, Y., Li, M., Dong, Z., Liu, Y., Ruan, H., Li, Y., Cao, S., et al. (2020) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2020.112903 · Cited by 108 · see citing works

FLT3 Inhibitors in Acute Myeloid Leukemia: Challenges and Recent Developments in Overcoming Resistance

Wang, Z., Cai, J., Cheng, J., Yang, W., Zhu, Y., Li, H., Lu, T., Chen, Y., & Lü, S. (2021) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.0c01851 · Cited by 102 · see citing works

Targeting estrogen receptor α for degradation with PROTACs: A promising approach to overcome endocrine resistance

Lin, X., Xiang, H., & Luo, G. (2020) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2020.112689 · Cited by 100 · see citing works

In vitro and in vivo degradation of programmed cell death ligand 1 (PD-L1) by a proteolysis targeting chimera (PROTAC)

Wang, Y., Zhou, Y., Cao, S., Sun, Y., Dong, Z., Li, C., Wang, H., Yao, Y., Yu, H., Song, X., et al. (2021) · Bioorganic Chemistry · doi:10.1016/j.bioorg.2021.104833 · Cited by 96 · see citing works

Proteolysis targeting chimeras (PROTACs) in cancer therapy

Ocaña, A., & Pandiella, A. (2020) · Journal of Experimental & Clinical Cancer Research · doi:10.1186/s13046-020-01672-1 · Cited by 87 · see citing works

Development of a Brigatinib degrader (SIAIS117) as a potential treatment for ALK positive cancer resistance

Sun, N., Ren, C., Kong, Y., Zhong, H., Chen, J., Li, Y., Zhang, J., Zhou, Y., Qiu, X., Lin, H., et al. (2020) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2020.112190 · Cited by 85 · see citing works

Targeting the Ubiquitin-Proteasome System for Cancer Therapeutics by Small-Molecule Inhibitors

LaPlante, G., & Zhang, W. (2021) · Cancers · doi:10.3390/cancers13123079 · Cited by 82 · see citing works

Structural and Physicochemical Features of Oral PROTACs

Schade, M., Scott, J. S., Hayhow, T. G., Pike, A., Terstiege, I., Ahlqvist, M. M., Johansson, J. R., Diène, C. R., Fallan, C., Balazs, A., et al. (2024) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.4c01017 · Cited by 80 · see citing works

Discovery of thalidomide-based PROTAC small molecules as the highly efficient SHP2 degraders

Yang, X., Wang, Z., Pei, Y., Song, N., Xu, L., Feng, B., Wang, H., Luo, X., Hu, X., Qiu, X., et al. (2021) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2021.113341 · Cited by 85 · see citing works

Degradation of Janus kinases in CRLF2-rearranged acute lymphoblastic leukemia

Chang, Y., Min, J., Jarusiewicz, J., Actis, M., Bradford, S. Y. C., Mayasundari, A., Yang, L., Chepyala, D., Alcock, L. J., Roberts, K. G., et al. (2021) · Blood · doi:10.1182/blood.2020006846 · Cited by 79 · see citing works

Recent Advances in PROTACs for Drug Targeted Protein Research

Yao, T., Xiao, H., Wang, H., & Xu, X. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms231810328 · Cited by 78 · see citing works

Advancing targeted protein degradation for metabolic diseases therapy

Zhou, Q., Xiao, H., Yang, F., Wang, Y., Li, P., & Zheng, Z. (2022) · Pharmacological Research · doi:10.1016/j.phrs.2022.106627 · Cited by 76 · see citing works

Advancing Strategies for Proteolysis-Targeting Chimera Design

Li, M., Zhi, Y., Liu, B., & Yao, Q. (2023) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.2c01555 · Cited by 76 · see citing works

Targeted protein degradation in vivo with Proteolysis Targeting Chimeras: Current status and future considerations

Watt, G. F., Scott‐Stevens, P., & Gaohua, L. (2019) · Drug Discovery Today Technologies · doi:10.1016/j.ddtec.2019.02.005 · Cited by 72 · see citing works

Recent progress in degradation of membrane proteins by PROTACs and alternative targeted protein degradation techniques

Chen, S., Cui, J., Chen, H., Yu, B., & Long, S. (2023) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2023.115911 · Cited by 70 · see citing works

Evolution of Cereblon-Mediated Protein Degradation as a Therapeutic Modality

Chamberlain, P. P., D’Agostino, L. A., Ellis, J. M., Hansen, J. D., Matyskiela, M. E., McDonald, J. J., Riggs, J. R., & Hamann, L. G. (2019) · ACS Medicinal Chemistry Letters · doi:10.1021/acsmedchemlett.9b00425 · Cited by 69 · see citing works

VHL-based PROTACs as potential therapeutic agents: Recent progress and perspectives

Wang, C., Zhang, Y., Wang, J., & Xing, D. (2021) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2021.113906 · Cited by 71 · see citing works

Applications of covalent chemistry in targeted protein degradation

Lu, D., Yu, X., Lin, H., Cheng, R., Monroy, E. Y., Qi, X., Wang, M. C., & Wang, J. (2022) · Chemical Society Reviews · doi:10.1039/d2cs00362g · Cited by 66 · see citing works

Small molecule PROTACs: an emerging technology for targeted therapy in drug discovery

Pei, H., Peng, Y., Zhao, Q., & Chen, Y. (2019) · RSC Advances · doi:10.1039/c9ra03423d · Cited by 65 · see citing works

A beginner’s guide to current synthetic linker strategies towards VHL-recruiting PROTACs

Zografou-Barredo, N. A., Hallatt, A. J., Goujon-Ricci, J., & Cano, C. (2023) · Bioorganic & Medicinal Chemistry · doi:10.1016/j.bmc.2023.117334 · Cited by 64 · see citing works

Targeted degradation of extracellular secreted and membrane proteins

Chen, X., Zhou, Y., Zhao, Y., & Tang, W. (2023) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2023.08.013 · Cited by 59 · see citing works

DNA framework-engineered chimeras platform enables selectively targeted protein degradation

Zhou, L.-M., Yu, B., Gao, M., Chen, R., Li, Z., Gu, Y., Bian, J., & Ma, Y. (2023) · Nature Communications · doi:10.1038/s41467-023-40244-7 · Cited by 57 · see citing works

Proteolysis-Targeting Chimera (PROTAC) Modification of Dovitinib Enhances the Antiproliferative Effect against FLT3-ITD-Positive Acute Myeloid Leukemia Cells

Cao, S., Ma, L., Liu, Y., Wei, M., Yao, Y., Li, C., Wang, R., Liu, N., Dong, Z., Li, X., et al. (2021) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.1c00996 · Cited by 55 · see citing works

Small molecule PROTACs in targeted therapy: An emerging strategy to induce protein degradation

Xi, M., Chen, Y., Yang, H., Xu, H., Du, K., Wu, C., Xu, Y., Deng, L., Luo, X., Yu, L., et al. (2019) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2019.04.036 · Cited by 56 · see citing works

Recent Advances in PROTAC-Based Antiviral Strategies

Ahmad, H., Zia, B., Husain, H., & Husain, A. (2023) · Vaccines · doi:10.3390/vaccines11020270 · Cited by 54 · see citing works

Degrading FLT3-ITD protein by proteolysis targeting chimera (PROTAC)

Chen, Y. X., Yuan, X., Tang, M., Shi, M., Yang, T., Liu, K., Deng, D., & Chen, L. (2021) · Bioorganic Chemistry · doi:10.1016/j.bioorg.2021.105508 · Cited by 52 · see citing works

Proteolysis Targeting Chimeras (PROTACs): A Perspective on Integral Membrane Protein Degradation

Ruffilli, C., Röth, S., Rodrigo, M., Boyd, H., Zelcer, N., & Moreau, K. (2022) · ACS Pharmacology & Translational Science · doi:10.1021/acsptsci.2c00142 · Cited by 50 · see citing works

Wu-5, a novel USP10 inhibitor, enhances crenolanib-induced FLT3-ITD-positive AML cell death via inhibiting FLT3 and AMPK pathways

Yu, M., Fang, Z., Wang, W., Zhang, Y., Bu, Z., Liu, M., Xiao, X., Zhang, Z., Zhang, X.-M., Cao, Y., et al. (2020) · Acta Pharmacologica Sinica · doi:10.1038/s41401-020-0455-x · Cited by 48 · see citing works

Modulation of FLT3-ITD and CDK9 in acute myeloid leukaemia cells by novel proteolysis targeting chimera (PROTAC)

Řezníčková, E., Krajčovičová, S., Peřina, M., Kovalová, M., Soural, M., & Kryštof, V. (2022) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2022.114792 · Cited by 43 · see citing works

Induced proximity-based therapeutic modalities

King, E. A., Meyers, M., & Nomura, D. K. (2025) · Nature Reviews Drug Discovery · doi:10.1038/s41573-025-01316-z · Cited by 42 · see citing works

Inhibitors, PROTACs and Molecular Glues as Diverse Therapeutic Modalities to Target Cyclin-Dependent Kinase

Rana, S., Mallareddy, J. R., Singh, S., Boghean, L., & Natarajan, A. (2021) · Cancers · doi:10.3390/cancers13215506 · Cited by 42 · see citing works

Therapeutic Targeting of FLT3 in Acute Myeloid Leukemia: Current Status and Novel Approaches

Tecik, M., & Adan, A. (2022) · OncoTargets and Therapy · doi:10.2147/ott.s384293 · Cited by 42 · see citing works

Native Mass Spectrometry for the Study of PROTAC GNE‐987‐Containing Ternary Complexes

Sternicki, L. M., Nonomiya, J., Liu, M., Mulvihill, M. M., & Quinn, R. J. (2021) · ChemMedChem · doi:10.1002/cmdc.202100113 · Cited by 40 · see citing works

Discovery of a Brigatinib Degrader SIAIS164018 with Destroying Metastasis-Related Oncoproteins and a Reshuffling Kinome Profile

Ren, C., Sun, N., Liu, H., Kong, Y., Sun, R., Qiu, X., Chen, J., Li, Y., Zhang, J., Zhou, Y., et al. (2021) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.1c00373 · Cited by 40 · see citing works

PROTACs, molecular glues and bifunctionals from bench to bedside: Unlocking the clinical potential of catalytic drugs

Maneiro, M., Vita, E. D., Conole, D., Kounde, C. S., Zhang, Q., & Tate, E. W. (2021) · Progress in medicinal chemistry · doi:10.1016/bs.pmch.2021.01.002 · Cited by 38 · see citing works

Cooperatively designed aptamer-PROTACs for spatioselective degradation of nucleocytoplasmic shuttling protein for enhanced combinational therapy

Liu, R., Liu, Z., Chen, M., Xing, H., Zhang, P., & Zhang, J. (2023) · Chemical Science · doi:10.1039/d3sc04249a · Cited by 38 · see citing works

Identification of Pyrrolo[2,3-d]pyrimidine-Based Derivatives as Potent and Orally Effective Fms-like Tyrosine Receptor Kinase 3 (FLT3) Inhibitors for Treating Acute Myelogenous Leukemia

Yuan, X., Chen, Y. X., Zhang, W., He, J., Lei, L., Tang, M., Liu, J., Li, M., Dou, C., Yang, T., et al. (2019) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.9b00223 · Cited by 38 · see citing works

Targeted protein degradation: current molecular targets, localization, and strategies

Pliatsika, D., Blatter, C., & Riedl, R. (2024) · Drug Discovery Today · doi:10.1016/j.drudis.2024.104178 · Cited by 37 · see citing works

PROTAC: targeted drug strategy. Principles and limitations

Koroleva, O. A., Dutikova, Y. V., Trubnikov, A. V., Zenov, F. A., Manasova, E. V., Shtil, A. A., & Kurkin, A. V. (2022) · Russian Chemical Bulletin · doi:10.1007/s11172-022-3659-z · Cited by 38 · see citing works

Development of Potent and Selective Coactivator-Associated Arginine Methyltransferase 1 (CARM1) Degraders

Xie, H., Bacabac, M. S., Ma, M., Kim, E., Wang, Y., Wu, W., Li, L., Xu, W., & Tang, W. (2023) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.3c00982 · Cited by 35 · see citing works

Discovery of a Novel Orally Bioavailable FLT3-PROTAC Degrader for Efficient Treatment of Acute Myeloid Leukemia and Overcoming Resistance of FLT3 Inhibitors

Wang, J., Rong, Q., Ye, L., Fang, B., Zhao, Y., Sun, Y., Zhou, H., Wang, D., He, J., Cui, Z., et al. (2024) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.4c00051 · Cited by 35 · see citing works

Scaffold hopping enables direct access to more potent PROTACs with in vivo activity

Burslem, G. M., Bondeson, D. P., & Crews, C. M. (2020) · Chemical Communications · doi:10.1039/d0cc02201b · Cited by 35 · see citing works

Ubiquitination and Ubiquitin-Like Modifications in Multiple Myeloma: Biology and Therapy

Wirth, M., Schick, M., Keller, U. B., & Krönke, J. (2020) · Cancers · doi:10.3390/cancers12123764 · Cited by 34 · see citing works

Targeting FMS-like tyrosine kinase 3 (FLT3) in acute myeloid leukemia: Novel molecular approaches and therapeutic challenges

Rataj, J., Górecki, L., Muthná, D., Sorf, A., Kryštof, V., Klener, P., Čečková, M., Řezáčová, M., & Korábečný, J. (2024) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2024.117788 · Cited by 31 · see citing works

Small-molecule PROTACs: Novel Agents for Cancer Therapy

Wan, Y., Yan, C., Gao, H. J., & Liu, T. (2020) · Future Medicinal Chemistry · doi:10.4155/fmc-2019-0340 · Cited by 32 · see citing works

Progress of small molecules for targeted protein degradation: PROTACs and other technologies

Zhao, H., Xin, M., & Zhang, S. (2023) · Drug Development Research · doi:10.1002/ddr.22026 · Cited by 31 · see citing works

Selective degradation of mutant FMS-like tyrosine kinase-3 requires BIM-dependent depletion of heat shock proteins

Halilovic, M., Abdelsalam, M. A. M., Zabkiewicz, J., Lazenby, M., Alvares, C. L., Schmidt, M., Brenner, W., Najafi, S., Oehme, I., Hieber, C., et al. (2024) · Leukemia · doi:10.1038/s41375-024-02405-5 · Cited by 28 · see citing works

FLT3-selective PROTAC: Enhanced safety and increased synergy with Venetoclax in FLT3-ITD mutated acute myeloid leukemia

Tan, Y., Xin, L., Wang, Q., Xu, R., Tong, X., Chen, G., Ma, L., Yang, F., Jiang, H., Zhang, N., et al. (2024) · Cancer Letters · doi:10.1016/j.canlet.2024.216933 · Cited by 27 · see citing works

Targeted protein degradation in hematologic malignancies: clinical progression towards novel therapeutics

Feng, Y., Hu, X., & Wang, X. (2024) · Biomarker Research · doi:10.1186/s40364-024-00638-1 · Cited by 27 · see citing works

Discovery of LWY713 as a potent and selective FLT3 PROTAC degrader with in vivo activity against acute myeloid leukemia

Liu, W., Bai, Y., Zhou, L., Jin, J., Zhang, M., Wang, Y., Lin, R., Huang, W., Ren, X., Ma, N., et al. (2023) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2023.115974 · Cited by 27 · see citing works

Recent Advances in FLT3 Inhibitors for Acute Myeloid Leukemia

Tong, L., Li, X., Hu, Y., & Liu, T. (2020) · Future Medicinal Chemistry · doi:10.4155/fmc-2019-0365 · Cited by 24 · see citing works

FLT3 inhibitors and novel therapeutic strategies to reverse AML resistance: An updated comprehensive review

Abdel‐Aziz, A. K., Dokla, E. M. E., & Saadeldin, M. K. (2023) · Critical Reviews in Oncology/Hematology · doi:10.1016/j.critrevonc.2023.104139 · Cited by 24 · see citing works

Development of Gilteritinib-Based Chimeric Small Molecules that Potently Induce Degradation of FLT3-ITD Protein

Ohoka, N., Suzuki, M., Uchida, T., Tsuji, G., Tsukumo, Y., Yoshida, M., Inoué, T., Demizu, Y., Ohki, H., & Naito, M. (2022) · ACS Medicinal Chemistry Letters · doi:10.1021/acsmedchemlett.2c00402 · Cited by 23 · see citing works

M1/M2 macrophage-targeted nanotechnology and PROTAC for the treatment of atherosclerosis

Ma, Y., Yang, X., Ning, K., & Guo, H. (2024) · Life Sciences · doi:10.1016/j.lfs.2024.122811 · Cited by 23 · see citing works

Targeted Protein Degradation: An Emerging Therapeutic Strategy in Cancer

Barghout, S. H. (2020) · Anti-Cancer Agents in Medicinal Chemistry · doi:10.2174/1871520620666200410082652 · Cited by 21 · see citing works

Structure-based discovery of receptor tyrosine kinase AXL degraders with excellent anti-tumor activity by selectively degrading AXL and inducing methuosis

Shi, W., Feng, Z., Chi, F., Zhou, J., Qiu, Q., Jiang, Y., Chen, S., Zhong, Y., Jia, H., Huang, W., et al. (2022) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2022.114253 · Cited by 21 · see citing works

ASDs of PROTACs: Spray-dried solid dispersions as enabling formulations

Hofmann, N., Harms, M., & Mäder, K. (2023) · International Journal of Pharmaceutics · doi:10.1016/j.ijpharm.2023.123725 · Cited by 21 · see citing works

Design, synthesis, and biological evaluation of small molecule PROTACs for potential anticancer effects

Da, Y., Liu, S., Lin, P., Wang, F., Yan, R., Shu, Y., & Lin, J. (2019) · Medicinal Chemistry Research · doi:10.1007/s00044-019-02485-4 · Cited by 20 · see citing works

Proteolysis-targeting chimeras: A promising technique in cancer therapy for gaining insights into tumor development

Lv, M., Hu, W., Zhang, S., He, L., Hu, C., & Yang, S. (2022) · Cancer Letters · doi:10.1016/j.canlet.2022.215716 · Cited by 19 · see citing works

The application of targeted protein degradation technologies to G protein‐coupled receptors

Keen, A. C., Jörg, M., & Halls, M. L. (2023) · British Journal of Pharmacology · doi:10.1111/bph.16079 · Cited by 19 · see citing works

Allostery in Disease: Anticancer Drugs, Pockets, and the Tumor Heterogeneity Challenge

Nussinov, R., Yavuz, B. R., & Jang, H. (2025) · Journal of Molecular Biology · doi:10.1016/j.jmb.2025.169050 · Cited by 19 · see citing works

Ternary Complex Modeling, Induced Fit Docking and Molecular Dynamics Simulations as a Successful Approach for the Design of VHL‐Mediated PROTACs Targeting the Kinase FLT3

Nassar, H., Sarnow, A., Celik, I., Abdelsalam, M. A. M., Robaa, D., & Sippl, W. (2025) · Archiv der Pharmazie · doi:10.1002/ardp.202500102 · Cited by 17 · see citing works

Degrading FLT3-ITD protein by proteolysis targeting chimera (PROTAC)

Chen, Y. X., Yuan, X., Tang, M., Shi, M., Yang, T., Liu, K., Deng, D., & Chen, L. (2021) · Bioorganic Chemistry · doi:10.1016/j.bioorg.2021.105508 · Cited by 52 · see citing works

Discovery of LWY713 as a potent and selective FLT3 PROTAC degrader with in vivo activity against acute myeloid leukemia

Liu, W., Bai, Y., Zhou, L., Jin, J., Zhang, M., Wang, Y., Lin, R., Huang, W., Ren, X., Ma, N., et al. (2023) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2023.115974 · Cited by 27 · see citing works

Progress in the Development of PROTAC Degraders of FLT3

Fan, B., Zhou, L., Xie, Y., Huang, W., & Wang, Z. (2025) · ChemistrySelect · doi:10.1002/slct.202503917

Discovery of FLT3-targeting PROTACs with potent antiproliferative activity against acute myeloid leukemia cells harboring FLT3 mutations

Wang, Z., Lu, X., Liu, C., Huang, F., Liu, C., Chen, Y., Liu, L., & Lü, S. (2024) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2024.116237 · Cited by 12 · see citing works

Synthesis and Biological Characterization of Dual-Specific Proteolysis Target Chimeras (Protacs) for the Kinases Flt3-Itd and Mapk14 with Antileukemic ActivityPreprint

Abdelsalam, M. A. M., Halilovic, M., Ashry, R., Nassar, H., Schmidt, M., Krämer, O. H., & Sippl, W. (2025) · SSRN Electronic Journal · doi:10.2139/ssrn.5336245