WZ4002

The Uses of WZ4002

A novel mutant-selective EGFR kinase inhibitor of EGFRL858R and EGFRL858R/T790M with IC50s of 2 nM and 8 nM, respectively.

The Uses of WZ4002

WZ 4002 is an EGFR phosphorylation inhibitor.

What are the applications of Application

WZ 4002 is an EGFR phosphorylation inhibitor

Definition

ChEBI: WZ4002 is a pyrimidine compound having a 2-methoxy-4-(4-methylpiperazin-1-yl)anilino group at the 2-position, a 3-(acryloylamino)phenoxy group at the 4-position, and a chloro substituent at the 5-position. It has a role as a tyrosine kinase inhibitor and an antineoplastic agent. It is a member of pyrimidines, a member of piperazines and an organochlorine compound.

Biological Activity

wz4002 is a novel mutant-selective epidermal growth factor receptor (egfr) kinase inhibitor that potently and irreversibly suppresses the atp-dependent auto-phosphorylation of both wild-type egfr and egfr mutants, including egfr dele746_a750/t790m, egfr l858r/t790m, egfr t790m, egfr dele746_a750 and egfr l858r, with inhibition constant ki of 13.6 nm, 1.8 nm, 4 nm, 5 nm, 3.9 nm and 8.5 nm respectively. although wz4002 is actively against egfr mutants rather than wild-type egfr at lower concentrations resulting in less toxicity in normal tissues, wild-type egfr is susceptible to higher concentrations of wz4002 as well as prolonged administration of wz4002, especially in tissues where it accumulates.

storage

Store at -20°C

References

[1]lee hj, schaefer g, heffron tp, shao l, ye x, sideris s, malek s, chan e, merchant m, la h, ubhayakar s, yauch rl, pirazzoli v, politi k, settleman j. noncovalent wild-type-sparing inhibitors of egfr t790m. cancer discov. 2013 feb;3(2):168-81. doi: 10.1158/2159-8290.cd-12-0357. epub 2012 dec 10.
[2]zhou w, ercan d, chen l, yun ch, li d, capelletti m, cortot ab, chirieac l, iacob re, padera r, engen jr, wong kk, eck mj, gray ns, jänne pa. novel mutant-selective egfr kinase inhibitors against egfr t790m. nature. 2009 dec 24;462(7276):1070-4. doi: 10.1038/nature08622.
[3]zannetti a, iommelli f, speranza a, salvatore m, del vecchio s. 3'-deoxy-3'-18f-fluorothymidine pet/ct to guide therapy with epidermal growth factor receptor antagonists and bcl-xl inhibitors in non-small cell lung cancer. j nucl med. 2012 mar;53(3):443-50. doi: 10.2967/jnumed.111.096503. epub 2012 feb 13.