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AZD9496 maleate Catalog No.GC35450

Size Price Stock Qty
10mM*1mL in DMSO
$148.00
In stock
2mg
$72.00
In stock
5mg
$121.00
In stock
10mg
$213.00
In stock
50mg
$723.00
In stock

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Sample solution is provided at 25 µL, 10mM.

Quality Control

Quality Control & SDS

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Protocol

Cell experiment:

Effect of AZD9496, Fulvestrant, and Tamoxifen on ERα peptide turnover in MCF-7 cells. Cells are grown in steroid-free conditions in SILAC media containing 13C615N4 L-arginine to label ERα peptide as “heavy” (blue line) and then switched to grow in media containing unlabeled L-arginine to label newly synthesized protein as “normal” (red line) with 0.1% DMSO, 300 nM Tamoxife, 100 nM AZD9496, or 100 nM Fulvestrant for the time indicated. Data shown is representative of two independent experiments[1].

Animal experiment:

Mice[1] In vivo efficacy of AZD9496 in MCF-7 xenograft model. MCF-7 xenografts, grown in male SCID mice, are dosed daily with either PEG/captisol (vehicle) or AZD9496 (0.02, 0.1, 0.5, 10, and 50 mg/kg, p.o., q.d.). Tumor growth is measured by caliper at regular intervals and mean tumor volumes plotted for each dosed group.

References:

[1]. Weir HM, et al. AZD9496: An Oral Estrogen Receptor Inhibitor That Blocks the Growth of ER-Positive and ESR1-Mutant Breast Tumors in Preclinical Models. Cancer Res. 2016 Jun 1;76(11):3307-18.
[2]. De Savi C, et al. Optimization of a Novel Binding Motif to (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 (AZD9496), a Potent and Orally Bioavailable Selective Estrogen Receptor Downregulator and Antagonist. J Med Chem. 2015 Oct 22;58(20):8128-40.

Chemical Properties

Cas No. 1639042-28-6 SDF Download SDF
Synonyms N/A
Chemical Name N/A
Canonical SMILES O=C(O)/C=C/C1=CC(F)=C([C@H]2N(CC(C)(F)C)[C@H](C)CC3=C2NC4=C3C=CC=C4)C(F)=C1.O=C(O)/C=C\C(O)=O
Formula C29H29F3N2O6 M.Wt 558.55
Solubility DMSO: ≥ 100 mg/mL (179.04 mM); H2O: < 0.1 mg/mL (insoluble) Storage Store at -20°C
General tips For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months.
Shipping Condition Evaluation sample solution : ship with blue ice
All other available size: ship with RT , or blue ice upon request
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Background

AZD9496 maleate is a potent and selective estrogen receptor (ERα)antagonist with IC50 of 0.28 nM. IC50: 0.28 nM (ERα antagonism), 0.14 nM (ERα downregulation), 0.82 nM (ERα binding)[1]

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].

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].

[1]. Weir HM, et al. AZD9496: An Oral Estrogen Receptor Inhibitor That Blocks the Growth of ER-Positive and ESR1-Mutant Breast Tumors in Preclinical Models. Cancer Res. 2016 Jun 1;76(11):3307-18. [2]. De Savi C, et al. Optimization of a Novel Binding Motif to (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 (AZD9496), a Potent and Orally Bioavailable Selective Estrogen Receptor Downregulator and Antagonist. J Med Chem. 2015 Oct 22;58(20):8128-40.