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AZ-5104

Names

[ CAS No. ]:
1421373-98-9

[ Name ]:
AZ-5104

[Synonym ]:
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

Biological Activity

[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.


[Related Small Molecules]

Osimertinib (AZD9291) | Tyrphostin B42 (AG-490) | Neratinib (HKI-272) | Genistein | (-)-Epigallocatechin gallate | AG-1478 | Dacomitinib (PF-00299804) | Irbinitinib | Poziotinib | Olmutinib | Sapitinib | AZD-3759 | Pyrotinib | Canertinib dihydrochloride | BMS-690514

Chemical & Physical Properties

[ Density]:
1.3±0.1 g/cm3

[ Molecular Formula ]:
C27H31N7O2

[ Molecular Weight ]:
485.581

[ Exact Mass ]:
485.253937

[ PSA ]:
98.41000

[ LogP ]:
2.90

[ Index of Refraction ]:
1.687

Related Compounds