product name AZD9496
Description: AZD9496 is a potent, orally bioavailable, and selective estrogen receptor downregulator (Ki=0.7 nM) and antagonist. AZD9496 showed pmol/L equipotent binding to both ERα and ERβ isoforms. AZD9496 directly targets ERα for downregulation in vitro. And it also antagonizes and downregulates mutant ER in vitro and in vivo. The IC50s of ERα binding, ERα downregulation, ERα antagonism for AZD9496 are 0.82, 0.14 and 0.28 nM, respectively.
References: Cancer Res. 2016 Jun 1;76(11):3307-18.
442.47
Formula
C25H25F3N2O2
CAS No.
1639042-08-2
Storage
-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)
DMSO: 88 mg/mL (198.9 mM)
Water: <1 mg/mL
Ethanol: 88 mg/mL (198.9 mM)
Solubility (In vivo)
Synonyms
AZD-9496
other peoduct :References PubMed ID：:http://www.ncbi.nlm.nih.gov/pubmed/19419310
| In Vitro |
In vitro activity: AZD9496 was identified as a nonsteroidal small-molecule inhibitor of ERα, which was a potent and selective antagonist and downregulator of ERα. In addition, AZD9496 could bind and downregulate clinically relevant ESR1 mutants. Kinase Assay: AZD9496 is a potent and orally bioavailable selective estrogen receptor downregulator(Ki=0.7 nM) and antagonist. Cell Assay: Cells were grown in steroid-free conditions in SILAC media containing 13C615N4 L-arginine to label ERα peptide as “heavy” and then switched to grow in media containing unlabeled l-arginine to label newly synthesized protein as “normal” with 0.1% DMSO, 300 nmol/L tamoxifen, 100 nmol/L AZD9496, or 100 nmol/L fulvestrant for the time indicated. |
|---|---|
| In Vivo | AZD9496 showed high oral bioavailability across three species (F% 63, 91, and 74, rat, mouse, and dog, respectively) with generally low volume and clearance across species, albeit a higher clearance in mouse. The percent free levels in human plasma of 0.15% were 5-fold higher than those measured for fulvestrant. AZD9496 is a potent, oral inhibitor of breast tumor growth in vivo. AZD9496 causes tumor regressions in combination with PI3K pathway and CDK4/6 inhibitors and in an estrogen-deprived ER+ model of resistance. This effect was accompanied by a dose-dependent decrease in PR protein levels. AZD9496 is currently being evaluated in a phase I clinical trial |
| Animal model | Sexually immature female Han Wistar rats |
| Formulation & Dosage | Dissolved in PEG/Captisol; 5 & 25 mg/kg once daily; Oral administration |
| References | Cancer Res. 2016 Jun 1;76(11):3307-18. |
