Structural Biology-Inspired Discovery of Novel KRAS–PDEδ Inhibitors

Targeting RAS signalling pathways in cancer therapy

Downward, J. (2003) · Nature reviews. Cancer · doi:10.1038/nrc969 · Cited by 3,262 · see citing works

RAS oncogenes: the first 30 years

Malumbres, M., & Barbacid, M. (2003) · Nature Reviews Cancer · doi:10.1038/nrc1097 · Cited by 1,902 · see citing works

An Acylation Cycle Regulates Localization and Activity of Palmitoylated Ras Isoforms

Rocks, O., Peyker, A., Kahms, M., Verveer, P., Koerner, C., Lumbierres, M., Kuhlmann, J., Waldmann, H., Wittinghofer, A., & Bastiaens, P. (2005) · Science · doi:10.1126/science.1105654 · Cited by 866 · see citing works

Small-molecule ligands bind to a distinct pocket in Ras and inhibit SOS-mediated nucleotide exchange activity

Maurer, T., Garrenton, L. S., Oh, A., Pitts, K., Anderson, D. J., Skelton, N. J., Fauber, B. P., Pan, B., Malek, S., Stokoe, D., et al. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1116510109 · Cited by 618 · see citing works

Targeting protein prenylation for cancer therapy

Berndt, N., Hamilton, A. D., & Sebti, S. M. (2011) · Nature Reviews Cancer · doi:10.1038/nrc3151 · Cited by 614 · see citing works

Small molecule inhibition of the KRAS–PDEδ interaction impairs oncogenic KRAS signalling

Zimmermann, G., Papke, B., Ismail, S., Vartak, N., Chandra, A., Hoffmann, M., Hahn, S. A., Triola, G., Wittinghofer, A., Bastiaens, P. I. H., et al. (2013) · Nature · doi:10.1038/nature12205 · Cited by 596 · see citing works

Discovery of Small Molecules that Bind to K‐Ras and Inhibit Sos‐Mediated Activation

Sun, Q., Burke, J. P., Phan, J., Burns, M. C., Olejniczak, E. T., Waterson, A. G., Lee, T., Rossanese, O. W., & Fesik, S. W. (2012) · Angewandte Chemie International Edition · doi:10.1002/anie.201201358 · Cited by 490 · see citing works

The GDI-like solubilizing factor PDEδ sustains the spatial organization and signalling of Ras family proteins

Chandra, A., Grecco, H. E., Pisupati, V., Perera, D., Cassidy, L., Skoulidis, F., Ismail, S. A., Hedberg, C., Hanzal-Bayer, M., Venkitaraman, A. R., et al. (2012) · Nature Cell Biology · doi:10.1038/ncb2394 · Cited by 325 · see citing works

An orthosteric inhibitor of the Ras-Sos interaction

Patgiri, A., Yadav, K. K., Arora, P. S., & Bar‐Sagi, D. (2011) · Nature Chemical Biology · doi:10.1038/nchembio.612 · Cited by 294 · see citing works

Arl2-GTP and Arl3-GTP regulate a GDI-like transport system for farnesylated cargo

Ismail, S. A., Chen, Y.-X., Rusinova, A., Chandra, A., Bierbaum, M., Gremer, L., Triola, G., Waldmann, H., Bastiaens, P. I. H., & Wittinghofer, A. (2011) · Nature Chemical Biology · doi:10.1038/nchembio.686 · Cited by 252 · see citing works

KRas Localizes to the Plasma Membrane by Spatial Cycles of Solubilization, Trapping and Vesicular Transport

Schmick, M., Vartak, N., Papke, B., Kovacevic, M., Truxius, D. C., Rossmannek, L., & Bastiaens, P. I. H. (2014) · Cell · doi:10.1016/j.cell.2014.02.051 · Cited by 243 · see citing works

Therapeutic intervention based on protein prenylation and associated modifications

Gelb, M. H., Brunsveld, L., Hrycyna, C. A., Michaelis, S., Tamanoi, F., Voorhis, W. C. V., & Waldmann, H. (2006) · Nature Chemical Biology · doi:10.1038/nchembio818 · Cited by 195 · see citing works

Targeting KRAS for diagnosis, prognosis, and treatment of pancreatic cancer: Hopes and realities

Bournet, B., Buscail, C., Muscari, F., Cordelier, P., & Buscail, L. (2015) · European Journal of Cancer · doi:10.1016/j.ejca.2015.11.012 · Cited by 164 · see citing works

Identification of pyrazolopyridazinones as PDEδ inhibitors

Papke, B., Murarka, S., Vogel, H. A., Martín‐Gago, P., Kovačević, M., Truxius, D. C., Fansa, E. K., Ismail, S., Zimmermann, G., Heinelt, K. F., et al. (2016) · Nature Communications · doi:10.1038/ncomms11360 · Cited by 164 · see citing works

Rapid Identification of Keap1–Nrf2 Small-Molecule Inhibitors through Structure-Based Virtual Screening and Hit-Based Substructure Search

Zhuang, C., Narayanapillai, S. C., Zhang, W., Sham, Y. Y., & Xing, C. (2014) · Journal of Medicinal Chemistry · doi:10.1021/jm4017174 · Cited by 156 · see citing works

Lipidated Ras and Rab Peptides and Proteins—Synthesis, Structure, and Function

Brunsveld, L., Kuhlmann, J., Alexandrov, K. A., Wittinghofer, A., Goody, R. S., & Waldmann, H. (2006) · Angewandte Chemie International Edition · doi:10.1002/anie.200600855 · Cited by 143 · see citing works

Photoreceptor cGMP Phosphodiesterase δ Subunit (PDEδ) Functions as a Prenyl-binding Protein

Zhang, H., Liu, X., Zhang, K., Chen, C.-K., Frederick, J. M., Prestwich, G. D., & Baehr, W. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m306559200 · Cited by 126 · see citing works

The δ Subunit of Retinal Rod cGMP Phosphodiesterase Regulates the Membrane Association of Ras and Rap GTPases

Nancy, V., Callebaut, I., Marjou, A. E., & de Gunzburg, J. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m109983200 · Cited by 124 · see citing works

A PDE6δ‐KRas Inhibitor Chemotype with up to Seven H‐Bonds and Picomolar Affinity that Prevents Efficient Inhibitor Release by Arl2

Martín‐Gago, P., Fansa, E. K., Klein, C. H., Murarka, S., Janning, P., Schürmann, M., Metz, M., Ismail, S., Schultz‐Fademrecht, C., Baumann, M., et al. (2017) · Angewandte Chemie International Edition · doi:10.1002/anie.201610957 · Cited by 89 · see citing works

Synthesis of the Rheb and K‐Ras4B GTPases

Chen, Y., Koch, S., Uhlenbrock, K., Weise, K., Das, D., Gremer, L., Brunsveld, L., Wittinghofer, A., Winter, R., Triola, G., et al. (2010) · Angewandte Chemie International Edition · doi:10.1002/anie.201001884 · Cited by 76 · see citing works

Structure Guided Design and Kinetic Analysis of Highly Potent Benzimidazole Inhibitors Targeting the PDEδ Prenyl Binding Site

Zimmermann, G., Schultz‐Fademrecht, C., Küchler, P., Murarka, S., Ismail, S., Triola, G., Nußbaumer, P., Wittinghofer, A., & Waldmann, H. (2014) · Journal of Medicinal Chemistry · doi:10.1021/jm500632s · Cited by 63 · see citing works

Stereoselectivity of drug action

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Ammonia-induced Na,K-ATPase/ouabain-mediated EGF receptor transactivation, MAPK/ERK and PI3K/AKT signaling and ROS formation cause astrocyte swelling

Dai, H., Song, D., Xu, J., Li, B., Hertz, L., & Peng, L. (2013) · Neurochemistry International · doi:10.1016/j.neuint.2013.09.005 · Cited by 62 · see citing works

Development of Pyridazinone Chemotypes Targeting the PDEδ Prenyl Binding Site

Murarka, S., Martín‐Gago, P., Schultz‐Fademrecht, C., Saabi, A. A., Baumann, M., Fansa, E. K., Ismail, S., Nußbaumer, P., Wittinghofer, A., & Waldmann, H. (2016) · Chemistry - A European Journal · doi:10.1002/chem.201603222 · Cited by 34 · see citing works

Structure-based development of PDEδ inhibitors

Martín‐Gago, P., Fansa, E. K., Wittinghofer, A., & Waldmann, H. (2016) · Biological Chemistry · doi:10.1515/hsz-2016-0272 · Cited by 27 · see citing works

Phosphodiesterase 6 subunits are expressed and altered in idiopathic pulmonary fibrosis

Nikolova, S., Günther, A., Savai, R., Weißmann, N., Ghofrani, H. A., Königshoff, M., Eickelberg, O., Klepetko, W., Voswinckel, R., Seeger, W., et al. (2010) · Respiratory Research · doi:10.1186/1465-9921-11-146 · Cited by 26 · see citing works

Mirror‐Image Packing Provides a Molecular Basis for the Nanomolar Equipotency of Enantiomers of an Experimental Herbicide

Bisson, C., Britton, K. L., Sedelnikova, S. E., et al. (2016) · Angewandte Chemie International Edition · doi:10.1002/anie.201607185 · Cited by 17 · see citing works

Endogenous cGMP-dependent protein kinase reverses EGF-induced MAPK/ERK signal transduction through phosphorylation of VASP at Ser239

Yan, T., GU, Y.-J., CAO, Z.-H., BIAN, X.-J., Lan, T., Sang, J., Jiang, L., Wang, Y., Qian, H., & Chen, Y. (2012) · Oncology Letters · doi:10.3892/ol.2012.851 · Cited by 14 · see citing works

Recent advances in the development of protein–protein interactions modulators: mechanisms and clinical trials

Lu, H., Zhou, Q., He, J., Jiang, Z., Peng, C., Tong, R., & Shi, J. (2020) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-020-00315-3 · Cited by 891 · 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

Discovery of Novel KRAS-PDEδ Inhibitors by Fragment-Based Drug Design

Chen, L., Zhuang, C., Lu, J., Jiang, Y., & Sheng, C. (2018) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.8b00057 · Cited by 33 · see citing works

Fragment-based drug discovery of triazole inhibitors to block PDEδ-RAS protein-protein interaction

Chen, D., Chen, Y., Lian, F., Chen, L., Li, Y., Cao, D., Wang, X., Chen, L., Li, J., Meng, T., et al. (2019) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2018.12.018 · Cited by 31 · see citing works

Discovery of novel KRAS‒PDEδ inhibitors with potent activity in patient-derived human pancreatic tumor xenograft models

Chen, L., Zhang, J., Wang, X., Li, Y., Zhou, L., Lu, X., Dong, G., & Sheng, C. (2022) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2021.07.009 · Cited by 20 · see citing works

Assessing the significance of KRAS G12C mutation: Clinicopathologic features, treatments, and survival outcomes in a real-world KRAS mutant non-small cell lung cancer cohort.

Cui, W., Franchini, F., Alexander, M., Officer, A., Wong, H., IJzerman, M. J., Desai, J., & Solomon, B. (2020) · Journal of Clinical Oncology · doi:10.1200/jco.2020.38.15_suppl.e19324 · Cited by 3 · see citing works

Lung Cancer and KRAS -Its Molecular Biology/Genetics and Therapeutic Strategy-

Koga, T., & Mitsudomi, T. (2022) · Haigan · doi:10.2482/haigan.62.188 · Cited by 1 · see citing works

Molecular profile of KRAS G12C-mutant colorectal and non-small-cell lung cancer

(2020) · doi:10.21203/rs.3.rs-108171/v1 · Cited by 2 · see citing works

127P RAS, RAF and NF1 oncogenic mutations in KRAS-mutated lung adenocarcinoma

Marinelli, D., Pisegna, S., Chiavassa, A., et al. (2022) · Annals of Oncology · doi:10.1016/j.annonc.2022.09.128

Molecular profile of KRAS G12C-mutant colorectal and non-small-cell lung cancer

Araujo, L. H., Souza, B. M., Leite, L. R., Parma, S. A. F., Lopes, N. P., Malta, F. S. V., & Freire, M. C. M. (2021) · BMC Cancer · doi:10.1186/s12885-021-07884-8 · Cited by 41 · see citing works