| CAS NO: | 1639042-08-2 |
| 规格: | ≥98% |
| 包装 | 价格(元) |
| 1mg | 电议 |
| 2mg | 电议 |
| 5mg | 电议 |
| 10mg | 电议 |
| 25mg | 电议 |
| 50mg | 电议 |
| 100mg | 电议 |
| 250mg | 电议 |
| 500mg | 电议 |
| Molecular Weight (MW) | 442.47 |
|---|---|
| Formula | C25H25F3N2O2 |
| CAS No. | 1639042-08-2 (free base); |
| 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) | |
| Other Info | Chemical Name: (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 InChi Key: DFBDRVGWBHBJNR-BBNFHIFMSA-N InChi Code: InChI=1S/C25H25F3N2O2/c1-14-10-17-16-6-4-5-7-20(16)29-23(17)24(30(14)13-25(2,3)28)22-18(26)11-15(12-19(22)27)8-9-21(31)32/h4-9,11-12,14,24,29H,10,13H2,1-3H3,(H,31,32)/b9-8+/t14-,24-/m1/s1 SMILES Code: 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 |
| Synonyms | AZD-9496; AZD9496; AZD 9496 |
| 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. |
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