PDBsum entry 5em5

Transferase/transferase inhibitor

PDB id: 5em5

Contents

Protein chain

298 a.a.

Ligands

5Q2

Waters ×8

PDB id:

5em5

Name:

Transferase/transferase inhibitor

Title:

Egfr kinase domain mutant "tmlr" with pyridone compound 2: 4-[2-(4- chlorophenyl)ethylamino]-~{n}-[4-(4-methylpiperazin-1-yl)phenyl]-2- oxidanylidene-1~{h}-pyridine-3-carboxamide

Structure:

Epidermal growth factor receptor. Chain: a. Synonym: proto-oncogenE C-erbb-1,receptor tyrosine-protein kinase erbb-1. Engineered: yes. Mutation: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: egfr, erbb, erbb1, her1. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108

Resolution:

2.65Å R-factor: 0.213 R-free: 0.223

Authors:

C.Eigenbrot,C.Yu

Key ref:

M.C.Bryan et al. (2016). Pyridones as Highly Selective, Noncovalent Inhibitors of T790M Double Mutants of EGFR. Acs Med Chem Lett, 7, 100-104. PubMed id: 26819674 DOI: 10.1021/acsmedchemlett.5b00428

Date:

05-Nov-15 Release date: 30-Dec-15

Protein chain

P00533  (EGFR_HUMAN) -  Epidermal growth factor receptor from Homo sapiens

Seq: 1210 a.a.

Struc: 298 a.a.*

* PDB and UniProt seqs differ at 2 residue positions (black crosses)

Enzyme reactions

• Enzyme class: E.C.2.7.10.1 - receptor protein-tyrosine kinase.
• Reaction: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H⁺

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

Added reference

DOI no: 10.1021/acsmedchemlett.5b00428

Acs Med Chem Lett 7:100-104 (2016)

PubMed id: 26819674

Pyridones as Highly Selective, Noncovalent Inhibitors of T790M Double Mutants of EGFR.

M.C.Bryan, D.J.Burdick, B.K.Chan, Y.Chen, S.Clausen, J.Dotson, C.Eigenbrot, R.Elliott, E.J.Hanan, R.Heald, P.Jackson, H.La, M.Lainchbury, S.Malek, S.E.Mann, H.E.Purkey, G.Schaefer, S.Schmidt, E.Seward, S.Sideris, S.Wang, I.Yen, C.Yu, T.P.Heffron.

ABSTRACT

The rapid advancement of a series of noncovalent inhibitors of T790M mutants of EGFR is discussed. The optimization of pyridone 1, a nonselective high-throughput screening hit, to potent molecules with high levels of selectivity over wtEGFR and the broader kinome is described herein.