6JRX

EGFR T790M/C797S in complex with compound 6i

Summary for 6JRX

• Entry DOI: 10.2210/pdb6jrx/pdb
• Descriptor: Epidermal growth factor receptor, N-{trans-4-[3-(2-chlorophenyl)-7-{[3-methyl-4-(4-methylpiperazin-1-yl)phenyl]amino}-2-oxo-3,4-dihydropyrimido[4,5-d]pyrimidin-1(2H)-yl]cyclohexyl}propanamide (3 entities in total)
• Functional Keywords: egfr t790m/c797s, inhibitor, complex, transferase
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 1
• Total formula weight: 38251.72

Authors

Zhu, S.J.,Yun, C.H. (deposition date: 2019-04-06, release date: 2020-04-15, Last modification date: 2024-03-27)

Primary citation

Yang, J.,Shibu, M.A.,Kong, L.,Luo, J.,BadrealamKhan, F.,Huang, Y.,Tu, Z.C.,Yun, C.H.,Huang, C.Y.,Ding, K.,Lu, X.
Design, Synthesis, and Structure-Activity Relationships of 1,2,3-Triazole Benzenesulfonamides as New Selective Leucine-Zipper and Sterile-alpha Motif Kinase (ZAK) Inhibitors.
J.Med.Chem., 63:2114-2130, 2020

PubMed Abstract: ZAK is a new promising target for discovery of drugs with activity against antihypertrophic cardiomyopathy (HCM). A series of 1,2,3-triazole benzenesulfonamides were designed and synthesized as selective ZAK inhibitors. One of these compounds, binds tightly to ZAK protein ( = 8.0 nM) and potently suppresses the kinase function of ZAK with single-digit nM (IC = 4.0 nM) and exhibits excellent selectivity in a KINOMEscan screening platform against a panel of 403 wild-type kinases. This compound dose dependently blocks p38/GATA-4 and JNK/c-Jun signaling and demonstrates promising in vivo anti-HCM efficacy upon oral administration in a spontaneous hypertensive rat (SHR) model. Compound may serve as a lead compound for new anti-HCM drug discovery.

PubMed: 31244114
DOI: 10.1021/acs.jmedchem.9b00664

Experimental method

X-RAY DIFFRACTION (2.201 Å)