1214265-57-2

Basic information

• Product Name: WZ8040
• Synonyms: WZ8040;N-[3-[[5-Chloro-2-[[4-(4-methyl-1-piperazinyl)phenyl]amino]-4-pyrimidinyl]thio]phenyl]-2-propenamide;N-(3-(5-chloro-2-(4-(4-methylpiperazin-1-yl)phenylamino)pyrimidin-4-ylthio)phenyl)acrylamide;N-[3-[[5-Chloro-2-[[4-(4-methyl-1-piperazinyl)phenyl]amino]-4-pyrimidinyl]thio]phenyl]-2-propenamide WZ8040;N-(3-((5-Chloro-2-((4-(4-methylpiperazin-1-yl)phenyl)amino)pyrimidin-4-yl)thio)phenyl)acrylami
• CAS NO: 1214265-57-2
• Molecular Formula: C₂₄H₂₅ClN₆OS
• Molecular Weight: 481.02
• EINECS: -0
• Product Categories: Inhibitors
• Mol File: 1214265-57-2.mol
• Article Data: 1

Chemical Properties

• Appearance: /
• Density: 1.37
• Solubility: ≥24.05 mg/mL in DMSO; insoluble in H2O; ≥2.61 mg/mL in EtOH with gentle warming and ultrasonic
• PKA: 12.94±0.70(Predicted)
• CAS DataBase Reference: WZ8040(CAS DataBase Reference)
• NIST Chemistry Reference: WZ8040(1214265-57-2)
• EPA Substance Registry System: WZ8040(1214265-57-2)

Safety Data

• Hazardous Substances Data: 1214265-57-2(Hazardous Substances Data)

Usage

Description

WZ8040 is an inhibitor of mutant EGF receptors (EGFRs) with IC50 values ranging from 2 to 306 nM in Ba/F3 cells. It is selective for EGFR mutants, including the EGFRDel E746_A750 and EGFRL858R mutations conferring gefitinib sensitivity and the EGFRDel E746_A750/T790M mutation conferring gefitinib resistance (IC50s = 2, 6, and 6 nM in Ba/F3 cells), over wild-type EGFR (IC50 = 1,820 nM in HN11 cells) but also inhibits ERBB2Ins G776V,C and wild-type ERBB2 (IC50s = 20 and 32 nM, respectively, in Ba/F3 cells). WZ8040 inhibits proliferation of PC-9 cells harboring the EGFRDel E746_A750 mutation and gefitinib-resistant PC-9 GR cells harboring the EGFRT790M resistant allele (EC50s = 6 and 8 nM, respectively).

Uses

WZ8040 is an irreversiblely EGFR T790M inhibitor (IC50<10nM).

references

[1] zhou w1, 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, j?nne pa. novel mutant-selective egfr kinase inhibitors against egfr t790m. nature. 2009 dec 24;462(7276):1070-4. doi: 10.1038/nature08622.

InChI:InChI=1S/C24H25ClN6OS/c1-3-22(32)27-18-5-4-6-20(15-18)33-23-21(25)16-26-24(29-23)28-17-7-9-19(10-8-17)31-13-11-30(2)12-14-31/h3-10,15-16H,1,11-14H2,2H3,(H,27,32)(H,26,28,29)

Relevant articles and documents

EGFR INHIBITORS AND METHODS OF TREATING DISORDERS

The present invention relates to novel pyrimidine, pyrrolo-pyrimidine, pyrrolo-pyridine, pyridine, purine and triazine compounds which are able to modulate epidermal growth factor receptor (EGFR), including Her-kinases, and the use of such compounds in the treatment of various diseases, disorders or conditions.