AZD9496

Cas No.:	1639042-08-2
Chemical Name:	(E)-3-[3,5-Difluoro-4-[(1S,3R)-2-(2-fluoro-2-methylpropyl)-3-methyl-1,3,4,9-tetrahydropyrido[3,4-b]indol-1-yl]phenyl]prop-2-enoic acid
Synonyms:	3-[3,5-Difluoro-4-[(1r,3r)-2-(2-fluoro-2-methylpropyl)-2,3,4,9-tetrahydro-3-methyl-1h-pyrido[3,4-b]indol-1-yl]phenyl]-2-propenoic acid;AZD9496;(E)-3-(3,5-difluoro-4-((1R,3R)-2-(2-fluoro-2-methylpropyl)-3-methyl-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indol-1-yl)phenyl)acrylic acid;AZD-9496;(E)-3-[3,5-Difluoro-4-[(1S,3R)-2-(2-fluoro-2-methylpropyl)-3-methyl-1,3,4,9-tetrahydropyrido[3,4-b]i
SMILES:	FC(C([H])([H])[H])(C([H])([H])[H])C([H])([H])N1[C@@]([H])(C2C(=C([H])C(/C(/[H])=C(\[H])/C(=O)O[H])=C([H])C=2F)F)C2=C(C3=C([H])C([H])=C([H])C([H])=C3N2[H])C([H])([H])[C@@]1([H])C([H])([H])[H]
Formula:	C25H25F3N2O2
M.Wt:	442.4734
Sotrage:	2 years -20°C Powder, 2 weeks 4°C in DMSO, 6 months -80°C in DMSO

Description:	AZD9496 is a potent and selective estrogen receptor (ERα) antagonist with an IC50 of 0.28 nM.
In Vivo:	Significant tumor growth inhibition is observed as low as 0.5 mg/kg dose in the estrogen-dependent MCF-7 xenograft model, where this effect is accompanied by a dose-dependent decrease in PR protein levels, demonstrating potent antagonist activity. Combining AZD9496 with PI3K pathway and CDK4/6 inhibitors lead to further growth-inhibitory effects compared with monotherapy alone. AZD9496, given once daily orally at 5 and 25 mg/kg produced statistically significant increases in uterine weight compared with the fulvestrant control (P<0.001) but significantly lower than tamoxifen (P=0.001)[1]. AZD9496 is also tested in a long-term estrogen deprived model (LTED), using the HCC-1428 LTED cell line that grows in the absence of estrogen and is thought to best represent a model of aromatase inhibition. AZD9496 shows significant activity, with a dose of 5 mg/kg giving tumor regressions in this model[2].
In Vitro:	The potency of AZD9496 with IC50 of 0.82 nM, 0.14 nM, and 0.28 nM in ERα binding, downregulation, and antagonism, respectively. AZD9496 significantly inhibits MCF-7 cell growth with EC50 of 0.04 nM[1]. Selectivity of AZD9496 over other tested nuclear hormone receptors is high: androgen receptor (AR), IC50=30 μM; glucocorticoid receptor (GR), IC50=9.2 μM; progesterone receptor (PR), IC50=0.54 μM[2].