AZD9496

SKU: orb1303489

Description

AZD9496 is an orally bioavailable, selective antagonist of estrogen receptor alpha (ERα) with potential antitumor activity. It has demonstrated efficacy in inhibiting the growth of ER-positive breast cancer cells in vitro and in xenograft models in vivo.

Research Area

Metabolism Research

Key Properties

• CAS Number: 1639042-08-2
• MW: 442.47
• Purity: 98.47%
• Formula: C₂₅H₂₅F₃N₂O₂
• SMILES: C(C(C)(C)F)N1[C@@H](C2=C(C=3C(N2)=CC=CC3)C[C@H]1C)C4=C(F)C=C(/C=C/C(O)=O)C=C4F
• Target: Estrogen/progestogen Receptor,Estrogen Receptor/ERR
• Solubility: H2O:< 1 mg/mL (insoluble or slightly soluble);DMSO:125 mg/mL (282.51 mM);Ethanol:82 mg/mL (185.32 mM);10% DMSO+40% PEG300+5% Tween 80+45% Saline:3.3 mg/mL (7.46 mM)

Bioactivity

• Target IC50:
  ERα:0.28 nM.
• 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 Clinicalal trial.
• In Vitro:
  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.
• Cell Research:
  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. (Only for Reference)

Storage & Handling

• Storage: Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice/Shipping at ambient temperature.
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

AZD9496, AZD-9496, AZD 9496, inhibit, Inhibitor, Estrogen Receptor, Estrogen Receptor/ERR, EstrogenReceptor, ERα, ERR, progestogen Receptor, progestogenReceptor

Compound Identifiers

PubChem CID

86287635