1421373-98-9

1421373-98-9 structure

Name: AZ-5104
Chemical Name: az5104
CAS Number: 1421373-98-9
Molecular Formula: C₂₇H₃₁N₇O₂
Molecular Weight: 485.581
Catalog: Research Areas Cancer
Create Date: 2017-01-16 08:28:20
Modify Date: 2024-01-09 22:48:59
AZ-5104 is an active, demethylated metabolite of AZD 9291. AZ-5104 is an EGFR inhibitor with IC50s of 1, 6, 1, 25 and 7 nM for EGFRL858R/T790M, EGFRL858R, EGFRL861Q, EGFR and ErbB4, respectively.

Name	az5104
Synonyms	metabolite of AZD9291 AZ 5104 Demethylated AZ9291 2-Propenamide, N-[2-[[2-(dimethylamino)ethyl]methylamino]-5-[[4-(1H-indol-3-yl)-2-pyrimidinyl]amino]-4-methoxyphenyl]- AZ-5104 N-[2-[[2-(Dimethylamino)ethyl]methylamino]-5-[[4-(1H-indol-3-yl)-2-pyrimidinyl]amino]-4-methoxyphenyl]-2-propenamide N-(5-((4-(1H-indol-3-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acrylamide N-(2-{[2-(Dimethylamino)ethyl](methyl)amino}-5-{[4-(1H-indol-3-yl)-2-pyrimidinyl]amino}-4-methoxyphenyl)acrylamide

Description	AZ-5104 is an active, demethylated metabolite of AZD 9291. AZ-5104 is an EGFR inhibitor with IC50s of 1, 6, 1, 25 and 7 nM for EGFRL858R/T790M, EGFRL858R, EGFRL861Q, EGFR and ErbB4, respectively.
Related Catalog	Research Areas >> Cancer
Target	EGFRL858R/T790M:1 nM (IC50) EGFRL858R:1 nM (IC50) EGFRL861Q:6 nM (IC50) EGFR:25 nM (IC50) ErbB4:7 nM (IC50) EGFRExon 19 deletion/T790M
In Vitro	AZ-5104 inhibits EGFR phosphorylation with IC50s of 2, 1, 2, 53, and 33 nM in H1975 (EGFRL858R/T790M), PC-9VanR (EGFRExon 19 deletion/T790M), PC-9 (EGFRExon 19 deletion), H2073 (WT), and LOVO (WT), respectively. AZ5104 exhibits a reduced selectivity margin against wild-type EGFR when compared to AZD9291. AZ5104 display minimal off-target activity against other non-HER family kinases, but has the potential to target both HER2 and HER4 kinase activity[1].
In Vivo	The metabolite, AZ5104 (5 mg/kg/day), is effective in shrinking tumors in both C/L858R and C/L+T mice[1].
Cell Assay	Cells were treated for 2 h with a dose-response of each drug (AZ-5104). Wild-type cells were stimulated for 10 minutes with 25 ng/mL of EGF before lysis. Level of EGFR phosphorylation was quantified in cell extracts using ELISA[1].
References	[1]. Cross DA, et al. AZD9291, an irreversible EGFR TKI, overcomes T790M-mediated resistance to EGFR inhibitors in lung cancer. Cancer Discov. 2014 Sep;4(9):1046-61.