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AZD9496

Cat. No. M6083
AZD9496 Structure
Size Price Availability Quantity
5mg USD 120 In stock
10mg USD 220 In stock
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Quality Control
  • Current batch:
  • Purity >98%
  • COA
  • MSDS
Biological Activity

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. 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.

Protocol
Cell Experiment
Cell lines MCF-7 cells
Preparation method 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.
Concentrations 100 nM
Incubation time 0, 10, 20, 30, 40, 50 h
Animal Experiment
Animal models Sexually immature female Han Wistar rats
Formulation PEG/Captisol
Dosages 5 and 25 mg/kg once daily
Administration oral gavage
Conversion of different model animals based on BSA (Value based on data from FDA Draft Guidelines)
Species Mouse Rat Rabbit Guinea pig Hamster Dog
Weight (kg) 0.02 0.15 1.8 0.4 0.08 10
Body Surface Area (m2) 0.007 0.025 0.15 0.05 0.02 0.5
Km factor 3 6 12 8 5 20
Animal A (mg/kg) = Animal B (mg/kg) multiplied by  Animal B Km
Animal A Km

For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for resveratrol of 11.2 mg/kg.

Chemical Information
Molecular Weight 442.47
Formula C25H25F3N2O2
CAS Number 1639042-08-2
Purity >98%
Solubility 88 mg/mL in DMSO
Storage at -20°C
References

AZD9496: An Oral Estrogen Receptor Inhibitor That Blocks the Growth of ER-Positive and ESR1-Mutant Breast Tumors in Preclinical Models.
Weir HM, et al. Cancer Res. 2016 Jun 1;76(11):3307-18. PMID: 27020862.

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.
De Savi C, et al. J Med Chem. 2015 Oct 22;58(20):8128-40. PMID: 26407012.

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  Catalog
Abmole Inhibitor Catalog 2017




Keywords: AZD9496 supplier, Epigenetic Reader Domain, inhibitors

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