AZD9496 maleate
Modify Date: 2024-01-04 10:28:25
AZD9496 maleate structure
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Common Name | AZD9496 maleate | ||
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| CAS Number | 1639042-28-6 | Molecular Weight | 558.55 | |
| Density | N/A | Boiling Point | N/A | |
| Molecular Formula | C29H29F3N2O6 | Melting Point | N/A | |
| MSDS | N/A | Flash Point | N/A | |
Use of AZD9496 maleateAZD9496 maleate is a potent and selective estrogen receptor (ERα)antagonist with IC50 of 0.28 nM. |
| Name | AZD9496 maleate |
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| Synonym | More Synonyms |
| Description | AZD9496 maleate is a potent and selective estrogen receptor (ERα)antagonist with IC50 of 0.28 nM. |
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| Related Catalog | |
| Target |
IC50: 0.28 nM (ERα antagonism), 0.14 nM (ERα downregulation), 0.82 nM (ERα binding)[1] |
| 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]. |
| 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]. |
| Cell Assay | 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 Admin | 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 |
| Molecular Formula | C29H29F3N2O6 |
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| Molecular Weight | 558.55 |
| Storage condition | 2-8℃ |
| AZD9496 (maleate) |