{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T19:10:25Z","timestamp":1792005025112,"version":"4.4.0"},"reference-count":81,"publisher":"Portland Press Ltd.","issue":"3","license":[{"start":{"date-parts":[[2021,6,8]],"date-time":"2021-06-08T00:00:00Z","timestamp":1623110400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2021,6,30]]},"abstract":"<jats:p>Cdc42 is a member of the Rho family of small GTPases and a key regulator of the actin cytoskeleton, controlling cell motility, polarity and cell cycle progression. It signals downstream of the master regulator Ras and is essential for cell transformation by this potent oncogene. Overexpression of Cdc42 is observed in several cancers, where it is linked to poor prognosis. As a regulator of both cell architecture and motility, deregulation of Cdc42 is also linked to tumour metastasis. Like Ras, Cdc42 and other components of the signalling pathways it controls represent important potential targets for cancer therapeutics. In this review, we consider the progress that has been made targeting Cdc42, its regulators and effectors, including new modalities and new approaches to inhibition. Strategies under consideration include inhibition of lipid modification, modulation of Cdc42\u2013GEF, Cdc42\u2013GDI and Cdc42-effector interactions, and direct inhibition of downstream effectors.<\/jats:p>","DOI":"10.1042\/bst20210112","type":"journal-article","created":{"date-parts":[[2021,6,8]],"date-time":"2021-06-08T14:23:23Z","timestamp":1623162203000},"page":"1443-1456","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":51,"title":["Progress in the therapeutic inhibition of Cdc42 signalling"],"prefix":"10.1042","volume":"49","author":[{"given":"Natasha P.","family":"Murphy","sequence":"first","affiliation":[{"name":"Department of Biochemistry, University of Cambridge, 80 Tennis Court Road, Cambridge CB2 1GA, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7890-7097","authenticated-orcid":false,"given":"Helen R.","family":"Mott","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, University of Cambridge, 80 Tennis Court Road, Cambridge CB2 1GA, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0978-5425","authenticated-orcid":false,"given":"Darerca","family":"Owen","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, University of Cambridge, 80 Tennis Court Road, Cambridge CB2 1GA, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"288","published-online":{"date-parts":[[2021,6,8]]},"reference":[{"key":"2021111916114508100_BST-2021-0112CC1","doi-asserted-by":"publisher","first-page":"3449","DOI":"10.1128\/mcb.17.6.3449","article-title":"Cdc42 regulates anchorage-independent growth and is necessary for Ras transformation","volume":"17","year":"1997","journal-title":"Mol. Cell. Biol."},{"key":"2021111916114508100_BST-2021-0112CC2","doi-asserted-by":"publisher","first-page":"1379","DOI":"10.1091\/mbc.9.6.1379","article-title":"Rhog GTPase controls a pathway that independently activates Rac1 and Cdc42Hs","volume":"9","year":"1998","journal-title":"Mol. Biol. Cell."},{"key":"2021111916114508100_BST-2021-0112CC3","doi-asserted-by":"publisher","first-page":"37317","DOI":"10.1371\/journal.pone.0037317","article-title":"Essential role of cdc42 in Ras-Induced transformation revealed by gene targeting","volume":"7","year":"2012","journal-title":"PLoS ONE"},{"key":"2021111916114508100_BST-2021-0112CC4","doi-asserted-by":"publisher","first-page":"R91","DOI":"10.1186\/bcr3487","article-title":"Cdc42 overexpression induces hyperbranching in the developing mammary gland by enhancing cell migration","volume":"15","year":"2013","journal-title":"Breast Cancer Res."},{"key":"2021111916114508100_BST-2021-0112CC5","doi-asserted-by":"publisher","first-page":"14151","DOI":"10.1038\/s41598-020-70822-4","article-title":"TRPV4 activates the Cdc42\/N-wasp pathway to promote glioblastoma invasion by altering cellular protrusions","volume":"10","year":"2020","journal-title":"Sci. Rep."},{"key":"2021111916114508100_BST-2021-0112CC6","doi-asserted-by":"publisher","first-page":"10918","DOI":"10.1073\/pnas.1704030114","article-title":"YAP\/TAZ-CDC42 signaling regulates vascular tip cell migration","volume":"114","year":"2017","journal-title":"Proc. Natl Acad. Sci. U.S.A."},{"key":"2021111916114508100_BST-2021-0112CC7","doi-asserted-by":"publisher","first-page":"4021","DOI":"10.1038\/onc.2013.362","article-title":"Rho guanine nucleotide exchange factors: regulators of Rho GTPase activity in development and disease","volume":"33","year":"2014","journal-title":"Oncogene"},{"key":"2021111916114508100_BST-2021-0112CC8","doi-asserted-by":"publisher","first-page":"1185","DOI":"10.1111\/j.1582-4934.2007.00098.x","article-title":"DLC-1:a Rho GTPase-activating protein and tumour suppressor: special review article","volume":"11","year":"2007","journal-title":"J. Cell. Mol. Med."},{"key":"2021111916114508100_BST-2021-0112CC9","doi-asserted-by":"publisher","DOI":"10.1042\/BST20200557","article-title":"Molecular subversion of Cdc42 signalling in cancer.","year":"2021","journal-title":"Biochem. Soc. Trans"},{"key":"2021111916114508100_BST-2021-0112CC10","doi-asserted-by":"publisher","first-page":"121","DOI":"10.1016\/j.chembiol.2020.12.012","article-title":"Inhibition of nonfunctional Ras","volume":"28","year":"2021","journal-title":"Cell Chem. Biol."},{"key":"2021111916114508100_BST-2021-0112CC11","doi-asserted-by":"publisher","first-page":"10984","DOI":"10.1096\/fj.202000550RR","article-title":"Activation of FAK\/Rac1\/Cdc42-GTPase signaling ameliorates impaired microglial migration response to A\u03b2 42 in triggering receptor expressed on myeloid cells 2 loss-of-function murine models","volume":"34","year":"2020","journal-title":"FASEB J."},{"key":"2021111916114508100_BST-2021-0112CC12","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/srep00809","article-title":"ROCK\/Cdc42-mediated microglial motility and gliapse formation lead to phagocytosis of degenerating dopaminergic neurons in vivo","volume":"2","year":"2012","journal-title":"Sci. Rep."},{"key":"2021111916114508100_BST-2021-0112CC13","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1186\/s13195-017-0320-4","article-title":"Rho GTPases as therapeutic targets in Alzheimer's disease","volume":"9","year":"2017","journal-title":"Alzheimer's Res. Ther."},{"key":"2021111916114508100_BST-2021-0112CC14","doi-asserted-by":"publisher","first-page":"8531","DOI":"10.1074\/jbc.M112.435941","article-title":"Characterization of a Cdc42 protein inhibitor and Its Use as a molecular probe","volume":"288","year":"2013","journal-title":"J. Biol. Chem."},{"key":"2021111916114508100_BST-2021-0112CC15","doi-asserted-by":"publisher","first-page":"923","DOI":"10.1016\/s0021-9258(18)54022-9","article-title":"Kinetic and structural analysis of the Mg2+-binding site of the guanine nucleotide-binding protein p21(H-ras)","volume":"268","year":"1993","journal-title":"J. Biol. Chem."},{"key":"2021111916114508100_BST-2021-0112CC16","doi-asserted-by":"publisher","first-page":"17527","DOI":"10.1038\/srep17527","article-title":"Distinct predictive performance of Rac1 and Cdc42 in cell migration","volume":"5","year":"2015","journal-title":"Sci. Rep."},{"key":"2021111916114508100_BST-2021-0112CC17","doi-asserted-by":"publisher","first-page":"68","DOI":"10.1182\/blood.V112.11.68.68","article-title":"Mobilization of hematopoitic stem\/Progenitor cells by a Cdc42 activity-specific inhibitor","volume":"112","year":"2008","journal-title":"Blood"},{"key":"2021111916114508100_BST-2021-0112CC18","doi-asserted-by":"publisher","first-page":"2215","DOI":"10.1158\/1535-7163.MCT-15-0419","article-title":"R-ketorolac targets Cdc42 and Rac1 and alters ovarian cancer cell behaviors critical for invasion and metastasis HHS public access","volume":"14","year":"2015","journal-title":"Mol. Cancer Ther."},{"key":"2021111916114508100_BST-2021-0112CC19","doi-asserted-by":"publisher","first-page":"6342","DOI":"10.1002\/anie.201900585","article-title":"Targeting the small GTPase superfamily through their regulatory proteins","volume":"59","year":"2020","journal-title":"Angew. Chem. Int. Ed. Engl."},{"key":"2021111916114508100_BST-2021-0112CC20","doi-asserted-by":"publisher","first-page":"201","DOI":"10.3389\/fcell.2020.00201","article-title":"Targeting Rac and Cdc42 GEFs in metastatic cancer","volume":"8","year":"2020","journal-title":"Front. Cell Dev. Biol."},{"key":"2021111916114508100_BST-2021-0112CC21","doi-asserted-by":"publisher","first-page":"498","DOI":"10.1038\/s41556-020-0488-x","article-title":"Systems analysis of RhoGEF and RhoGAP regulatory proteins reveals spatially organized RAC1 signalling from integrin adhesions","volume":"22","year":"2020","journal-title":"Nat. Cell Biol."},{"key":"2021111916114508100_BST-2021-0112CC22","doi-asserted-by":"publisher","first-page":"120","DOI":"10.1038\/s41556-019-0438-7","article-title":"Mapping the proximity interaction network of the Rho-family GTPases reveals signalling pathways and regulatory mechanisms","volume":"22","year":"2020","journal-title":"Nat. Cell Biol."},{"key":"2021111916114508100_BST-2021-0112CC23","doi-asserted-by":"publisher","first-page":"222","DOI":"10.3389\/fcell.2020.00222","article-title":"Targeting Rho GTPase signaling networks in cancer","volume":"8","year":"2020","journal-title":"Front. Cell Dev. Biol."},{"key":"2021111916114508100_BST-2021-0112CC24","doi-asserted-by":"publisher","first-page":"468","DOI":"10.1038\/nsb796","article-title":"Structural basis for the selective activation of rho gtpases by dbl exchange factors","volume":"9","year":"2002","journal-title":"Nat. Struct. Biol."},{"key":"2021111916114508100_BST-2021-0112CC25","doi-asserted-by":"publisher","first-page":"13282","DOI":"10.1021\/bi050591b","article-title":"A Cdc42 mutant specifically activated by intersectin","volume":"44","year":"2005","journal-title":"Biochemistry"},{"key":"2021111916114508100_BST-2021-0112CC26","doi-asserted-by":"publisher","first-page":"4828","DOI":"10.1038\/onc.2011.643","article-title":"Intersectin 1 is required for neuroblastoma tumorigenesis","volume":"31","year":"2012","journal-title":"Oncogene"},{"key":"2021111916114508100_BST-2021-0112CC27","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1186\/s12943-016-0543-1","article-title":"Rac1-mediated cytoskeleton rearrangements induced by intersectin-1s deficiency promotes lung cancer cell proliferation, migration and metastasis","volume":"15","year":"2016","journal-title":"Mol. Cancer"},{"key":"2021111916114508100_BST-2021-0112CC28","doi-asserted-by":"publisher","first-page":"1261","DOI":"10.1073\/pnas.1116051110","article-title":"Small molecule targeting Cdc42-intersectin interaction disrupts Golgi organization and suppresses cell motility","volume":"110","year":"2013","journal-title":"Proc. Natl Acad. Sci. U.S.A."},{"key":"2021111916114508100_BST-2021-0112CC29","doi-asserted-by":"publisher","first-page":"740","DOI":"10.1080\/15384047.2018.1564559","article-title":"Inhibition of Cdc42\u2013intersectin interaction by small molecule ZCL367 impedes cancer cell cycle progression, proliferation, migration, and tumor growth","volume":"20","year":"2019","journal-title":"Cancer Biol. Ther."},{"key":"2021111916114508100_BST-2021-0112CC30","doi-asserted-by":"publisher","first-page":"749","DOI":"10.1038\/s41375-018-0251-5","article-title":"Rational identification of a Cdc42 inhibitor presents a new regimen for long-term hematopoietic stem cell mobilization","volume":"33","year":"2019","journal-title":"Leukemia"},{"key":"2021111916114508100_BST-2021-0112CC31","doi-asserted-by":"publisher","first-page":"958","DOI":"10.3389\/fonc.2019.00958","article-title":"Rational targeting of Cdc42 overcomes drug resistance of multiple myeloma","volume":"9","year":"2019","journal-title":"Front. Oncol."},{"key":"2021111916114508100_BST-2021-0112CC32","doi-asserted-by":"publisher","first-page":"e13208","DOI":"10.1111\/acel.13208","article-title":"Inhibition of Cdc42 activity extends lifespan and decreases circulating inflammatory cytokines in aged female C57BL\/6 mice","volume":"19","year":"2020","journal-title":"Aging Cell"},{"key":"2021111916114508100_BST-2021-0112CC33","doi-asserted-by":"publisher","first-page":"7618","DOI":"10.1073\/pnas.0307512101","article-title":"Rational design and characterization of a Rac GTPase-specific small molecule inhibitor","volume":"101","year":"2004","journal-title":"Proc. Natl Acad. Sci. U.S.A."},{"key":"2021111916114508100_BST-2021-0112CC34","doi-asserted-by":"publisher","first-page":"13228","DOI":"10.1074\/jbc.M111.334524","article-title":"Characterization of EHop-016, novel small molecule inhibitor of Rac GTPase","volume":"287","year":"2012","journal-title":"J. Biol. Chem."},{"key":"2021111916114508100_BST-2021-0112CC35","doi-asserted-by":"publisher","first-page":"2010","DOI":"10.1002\/1878-0261.12548","article-title":"RAC1 inhibition reverses cisplatin resistance in esophageal squamous cell carcinoma and induces downregulation of glycolytic enzymes","volume":"13","year":"2019","journal-title":"Mol. Oncol."},{"key":"2021111916114508100_BST-2021-0112CC36","doi-asserted-by":"publisher","first-page":"805","DOI":"10.1158\/1535-7163.MCT-16-0442","article-title":"Characterization of a dual Rac\/Cdc42 inhibitor MBQ-167 in metastatic cancer","volume":"16","year":"2017","journal-title":"Mol. Cancer Ther."},{"key":"2021111916114508100_BST-2021-0112CC37","doi-asserted-by":"publisher","first-page":"17981","DOI":"10.1021\/acsomega.9b01641","article-title":"Pharmacokinetics of the Rac\/Cdc42 inhibitor MBQ-167 in mice by supercritical fluid chromatography-tandem mass spectrometry","volume":"4","year":"2019","journal-title":"ACS Omega"},{"key":"2021111916114508100_BST-2021-0112CC38","doi-asserted-by":"publisher","first-page":"4087","DOI":"10.1021\/jm8015987","article-title":"Virtual screening approach for the identification of new Rac1 inhibitors","volume":"52","year":"2009","journal-title":"J. Med. Chem."},{"key":"2021111916114508100_BST-2021-0112CC39","doi-asserted-by":"publisher","first-page":"e0074924","DOI":"10.1371\/journal.pone.0074924","article-title":"A Rac1\/Cdc42 GTPase-specific small molecule inhibitor suppresses growth of primary human prostate cancer xenografts and prolongs survival in mice","volume":"8","year":"2013","journal-title":"PLoS ONE"},{"key":"2021111916114508100_BST-2021-0112CC40","doi-asserted-by":"publisher","first-page":"295","DOI":"10.1186\/1479-5876-11-295","article-title":"Targeting Cdc42 with the small molecule drug AZA197 suppresses primary colon cancer growth and prolongs survival in a preclinical mouse xenograft model by downregulation of PAK1 activity","volume":"11","year":"2013","journal-title":"J. Transl. Med."},{"key":"2021111916114508100_BST-2021-0112CC41","doi-asserted-by":"publisher","first-page":"9913","DOI":"10.1073\/pnas.170290597","article-title":"Binding site of brefeldin A at the interface between the small G protein ADP-ribosylation factor 1 (ARF1) and the nucleotide-exchange factor Sec7 domain","volume":"97","year":"2000","journal-title":"Proc. Natl Acad. Sci. U.S.A."},{"key":"2021111916114508100_BST-2021-0112CC42","unstructured":"Gray,\n            J.L\n          , Antunez,C.J, Krojer,T., Fairhead,M., Talon,R., Burgess-Brown,N.et al. (2019) Human Kalirin\/RAC1 GEF\/GTPase Complex. https:\/\/doi.org\/10.5281\/ZENODO.4134737"},{"key":"2021111916114508100_BST-2021-0112CC43","doi-asserted-by":"publisher","first-page":"2000098","DOI":"10.1002\/advs.202000098","article-title":"Covalent inhibitors allosterically block the activation of Rho family proteins and suppress cancer cell invasion","volume":"7","year":"2020","journal-title":"Adv. Sci."},{"key":"2021111916114508100_BST-2021-0112CC44","doi-asserted-by":"publisher","first-page":"10072","DOI":"10.1021\/jm501412a","article-title":"Chemical and computational methods for the characterization of covalent reactive groups for the prospective design of irreversible inhibitors","volume":"57","year":"2014","journal-title":"J. Med. Chem."},{"key":"2021111916114508100_BST-2021-0112CC45","doi-asserted-by":"publisher","first-page":"2617","DOI":"10.1039\/c9cs00720b","article-title":"Advances in covalent kinase inhibitors","volume":"49","year":"2020","journal-title":"Chem. Soc. Rev."},{"key":"2021111916114508100_BST-2021-0112CC46","doi-asserted-by":"publisher","first-page":"548","DOI":"10.1038\/nature12796","article-title":"K-Ras(G12C) inhibitors allosterically control GTP affinity and effector interactions","volume":"503","year":"2013","journal-title":"Nature"},{"key":"2021111916114508100_BST-2021-0112CC47","doi-asserted-by":"publisher","first-page":"54","DOI":"10.1158\/2159-8290.CD-19-1167","article-title":"The KRASG12C inhibitor MRTX849 provides insight toward therapeutic susceptibility of KRAS-mutant cancers in mouse models and patients","volume":"10","year":"2020","journal-title":"Cancer Discov."},{"key":"2021111916114508100_BST-2021-0112CC48","doi-asserted-by":"publisher","first-page":"217","DOI":"10.1038\/s41586-019-1694-1","article-title":"The clinical KRAS(G12C) inhibitor AMG 510 drives anti-tumour immunity","volume":"575","year":"2019","journal-title":"Nature"},{"key":"2021111916114508100_BST-2021-0112CC49","doi-asserted-by":"publisher","first-page":"533","DOI":"10.1038\/nrd.2016.29","article-title":"Small molecules, big targets: drug discovery faces the protein-protein interaction challenge","volume":"15","journal-title":"Nat. Rev. Drug Discov."},{"key":"2021111916114508100_BST-2021-0112CC50","doi-asserted-by":"publisher","first-page":"2866","DOI":"10.1074\/jbc.RA119.010077","article-title":"The discovery and maturation of peptide biologics targeting the small G-protein Cdc42: a bioblockade for Ras-driven signaling","volume":"295","year":"2020","journal-title":"J. Biol. Chem."},{"key":"2021111916114508100_BST-2021-0112CC51","doi-asserted-by":"publisher","first-page":"e24165","DOI":"10.1002\/pep2.24165","article-title":"Therapeutic peptides targeting the Ras superfamily","volume":"112","year":"2020","journal-title":"Pept. Sci."},{"key":"2021111916114508100_BST-2021-0112CC52","doi-asserted-by":"publisher","first-page":"779","DOI":"10.1038\/nprot.2011.331","article-title":"Flexizymes for genetic code reprogramming","volume":"6","year":"2011","journal-title":"Nat. Protoc."},{"key":"2021111916114508100_BST-2021-0112CC53","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1002\/bip.22767","article-title":"Approaches to the stabilization of bioactive epitopes by grafting and peptide cyclization","volume":"106","year":"2016","journal-title":"Biopolymers"},{"key":"2021111916114508100_BST-2021-0112CC54","doi-asserted-by":"publisher","first-page":"512","DOI":"10.1021\/acscentsci.8b00098","article-title":"Machine learning to predict cell-penetrating peptides for antisense delivery","volume":"4","year":"2018","journal-title":"ACS Cent. Sci."},{"key":"2021111916114508100_BST-2021-0112CC55","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s41598-019-41005-7","article-title":"A peptide-Nanoparticle system with improved efficacy against multidrug resistant bacteria","volume":"9","year":"2019","journal-title":"Sci. Rep."},{"key":"2021111916114508100_BST-2021-0112CC56","doi-asserted-by":"publisher","first-page":"1544","DOI":"10.1016\/j.chembiol.2019.08.009","article-title":"A targeted protein degradation cell-based screening for nanobodies selective toward the cellular RHOB GTP-Bound conformation","volume":"26","year":"2019","journal-title":"Cell Chem. Biol."},{"key":"2021111916114508100_BST-2021-0112CC57","doi-asserted-by":"publisher","first-page":"153","DOI":"10.1517\/13543784.2011.546344","article-title":"Mechanisms of drug resistance in kinases","volume":"20","year":"2011","journal-title":"Expert Opin. Investig. Drugs."},{"key":"2021111916114508100_BST-2021-0112CC58","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1016\/j.phrs.2015.10.021","article-title":"Classification of small molecule protein kinase inhibitors based upon the structures of their drug-enzyme complexes","volume":"103","year":"2016","journal-title":"Pharmacol. Res."},{"key":"2021111916114508100_BST-2021-0112CC59","doi-asserted-by":"publisher","first-page":"356","DOI":"10.1016\/j.bbapap.2017.10.004","article-title":"PAK4 crystal structures suggest unusual kinase conformational movements","volume":"1866","year":"2018","journal-title":"Biochim. Biophys. Acta Proteins Proteomics"},{"key":"2021111916114508100_BST-2021-0112CC60","doi-asserted-by":"publisher","first-page":"9446","DOI":"10.1073\/pnas.0911863107","article-title":"Small-molecule p21-activated kinase inhibitor PF-3758309 is a potent inhibitor of oncogenic signaling and tumor growth","volume":"107","year":"2010","journal-title":"Proc. Natl Acad. Sci. U.S.A."},{"key":"2021111916114508100_BST-2021-0112CC61","doi-asserted-by":"publisher","first-page":"22","DOI":"10.3389\/fphar.2013.00022","article-title":"Tumor P-glycoprotein correlates with efficacy of PF-3758309 in in vitro and in vivo models of colorectal cancer","volume":"4","year":"2013","journal-title":"Front. Pharmacol."},{"key":"2021111916114508100_BST-2021-0112CC62","doi-asserted-by":"publisher","first-page":"76","DOI":"10.1158\/1535-7163.MCT-16-0205","article-title":"Novel p21-activated kinase 4 (PAK4) allosteric modulators overcome drug resistance and stemness in pancreatic ductal adenocarcinoma","volume":"16","year":"2017","journal-title":"Mol. Cancer Ther."},{"key":"2021111916114508100_BST-2021-0112CC63","doi-asserted-by":"publisher","first-page":"2119","DOI":"10.1158\/1535-7163.MCT-16-0197","article-title":"Dual and specific inhibition of NAMPT and PAK4 by KPT-9274 decreases kidney cancer growth","volume":"15","year":"2016","journal-title":"Mol. Cancer Ther."},{"key":"2021111916114508100_BST-2021-0112CC64","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s41467-017-02349-8","article-title":"Target identification of small molecules using large-scale CRISPR-Cas mutagenesis scanning of essential genes","volume":"9","year":"2018","journal-title":"Nat. Commun."},{"key":"2021111916114508100_BST-2021-0112CC65","doi-asserted-by":"publisher","first-page":"622","DOI":"10.3389\/fonc.2018.00622","article-title":"NAD metabolism in cancer therapeutics","volume":"8","year":"2018","journal-title":"Front. Oncol."},{"key":"2021111916114508100_BST-2021-0112CC66","doi-asserted-by":"publisher","first-page":"1902","DOI":"10.3390\/cancers11121902","article-title":"PAK4-NAMPT dual inhibition as a novel strategy for therapy resistant pancreatic neuroendocrine tumors","volume":"11","year":"2019","journal-title":"Cancers (Basel)"},{"key":"2021111916114508100_BST-2021-0112CC67","doi-asserted-by":"publisher","first-page":"293","DOI":"10.1517\/13543776.2012.668758","article-title":"P21-Activated kinase inhibitors: a patent review","volume":"22","year":"2012","journal-title":"Expert Opin. Ther. Pat."},{"key":"2021111916114508100_BST-2021-0112CC68","doi-asserted-by":"publisher","first-page":"111","DOI":"10.1021\/jm501613q","article-title":"Inhibitors of p21-activated kinases (PAKs)","volume":"58","year":"2015","journal-title":"J. Med. Chem."},{"key":"2021111916114508100_BST-2021-0112CC69","doi-asserted-by":"publisher","first-page":"54","DOI":"10.1186\/s12964-014-0054-x","article-title":"A novel small-molecule MRCK inhibitor blocks cancer cell invasion","volume":"12","year":"2014","journal-title":"Cell Commun. Signal."},{"key":"2021111916114508100_BST-2021-0112CC70","doi-asserted-by":"publisher","first-page":"2096","DOI":"10.1158\/0008-5472.CAN-17-2870","article-title":"Discovery of potent and selective MRCK inhibitors with therapeutic effect on skin cancer","volume":"78","year":"2018","journal-title":"Cancer Res."},{"key":"2021111916114508100_BST-2021-0112CC71","doi-asserted-by":"publisher","first-page":"255","DOI":"10.1038\/ncb1230","article-title":"Cdc42-MRCK and Rho-ROCK signalling cooperate in myosin phosphorylation and cell invasion","volume":"7","year":"2005","journal-title":"Nat. Cell Biol."},{"key":"2021111916114508100_BST-2021-0112CC72","doi-asserted-by":"publisher","first-page":"185","DOI":"10.1016\/j.canlet.2013.04.004","article-title":"ACK1 tyrosine kinase: targeted inhibition to block cancer cell proliferation","volume":"338","year":"2013","journal-title":"Cancer Lett."},{"key":"2021111916114508100_BST-2021-0112CC73","doi-asserted-by":"publisher","first-page":"270","DOI":"10.1073\/pnas.0609412103","article-title":"Identification of NVP-TAE684, a potent, selective, and efficacious inhibitor of NPM-ALK","volume":"104","year":"2007","journal-title":"Proc. Natl Acad. Sci. U.S.A."},{"key":"2021111916114508100_BST-2021-0112CC74","doi-asserted-by":"publisher","first-page":"1046","DOI":"10.1038\/nbt.1990","article-title":"Comprehensive analysis of kinase inhibitor selectivity","volume":"29","year":"2011","journal-title":"Nat. Biotechnol."},{"key":"2021111916114508100_BST-2021-0112CC75","doi-asserted-by":"publisher","first-page":"3197","DOI":"10.1042\/BCJ20190517","article-title":"Lessons from LIMK1 enzymology and their impact on inhibitor design","volume":"476","year":"2019","journal-title":"Biochem. J."},{"key":"2021111916114508100_BST-2021-0112CC76","doi-asserted-by":"publisher","first-page":"445","DOI":"10.1016\/j.ejmech.2018.06.016","article-title":"Recent advances in the rational design and development of LIM kinase inhibitors are not enough to enter clinical trials","volume":"155","year":"2018","journal-title":"Eur. J. Med. Chem."},{"key":"2021111916114508100_BST-2021-0112CC77","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1021\/ml500242y","article-title":"Discovery of a type III inhibitor of LIM kinase 2 that binds in a DFG-out conformation","volume":"6","year":"2015","journal-title":"ACS Med. Chem. Lett."},{"key":"2021111916114508100_BST-2021-0112CC78","doi-asserted-by":"publisher","first-page":"552","DOI":"10.1038\/s41557-019-0237-6","article-title":"Dual chemical probes enable quantitative system-wide analysis of protein prenylation and prenylation dynamics","volume":"11","year":"2019","journal-title":"Nat. Chem."},{"key":"2021111916114508100_BST-2021-0112CC79","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1038\/nchembio751","article-title":"Secramine inhibits Cdc42-dependent functions in cells and Cdc42 activation in vitro","volume":"2","year":"2006","journal-title":"Nat. Chem. Biol."},{"key":"2021111916114508100_BST-2021-0112CC80","doi-asserted-by":"publisher","first-page":"15136","DOI":"10.1074\/jbc.RA118.003290","article-title":"Bond swapping from a charge cloud allows flexible coordination of upstream signals through WASP: multiple regulatory roles for the WASP basic region","volume":"293","year":"2018","journal-title":"J. Biol. Chem."},{"key":"2021111916114508100_BST-2021-0112CC81","doi-asserted-by":"publisher","first-page":"1243","DOI":"10.1021\/bi991567z","article-title":"Residues in Cdc42 that specify binding to individual CRIB effector proteins","volume":"39","year":"2000","journal-title":"Biochemistry"}],"container-title":["Biochemical Society Transactions"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/portlandpress.com\/biochemsoctrans\/article-pdf\/49\/3\/1443\/916196\/bst-2021-0112c.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/portlandpress.com\/biochemsoctrans\/article-pdf\/49\/3\/1443\/916196\/bst-2021-0112c.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,11,19]],"date-time":"2021-11-19T16:31:29Z","timestamp":1637339489000},"score":1,"resource":{"primary":{"URL":"https:\/\/portlandpress.com\/biochemsoctrans\/article\/49\/3\/1443\/228967\/Progress-in-the-therapeutic-inhibition-of-Cdc42"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,6,8]]},"references-count":81,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2021,6,8]]},"published-print":{"date-parts":[[2021,6,30]]}},"URL":"https:\/\/doi.org\/10.1042\/bst20210112","relation":{},"ISSN":["0300-5127","1470-8752"],"issn-type":[{"value":"0300-5127","type":"print"},{"value":"1470-8752","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,6,8]]}}}