AZD9496 |
Catalog No.GC14405 |
estrogen receptor inhibitor, orally active
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 1639042-08-2
Sample solution is provided at 25 µL, 10mM.
Quality Control & SDS
- View current batch:
- Purity: >99.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Cell experiment: | 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 experiment: | 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: [1]. Weir HM, et al. AZD9496: An Oral Estrogen Receptor Inhibitor That Blocks the Growth of ER-Positive and ESR1-Mutant Breast Tumors in Preclinical Models. Cancer Res. 2016 Jun 1;76(11):3307-18. |
IC50: 0.82, 0.14 and 0.28 nM for ERα binding, ERα downregulation, ERα antagonism, respectively
AZD9496 is an orally active estrogen receptor inhibitor.
Estrogen receptors (ERs) are a group of proteins presented inside and on cells, and they are receptors that are activated by the hormoneestrogen. ERs are found to be over-expressed in about 70% of breast cancer cases, referred to as "ER-positive".
In vitro: 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 [1].
In vivo: Animal study reported that significant tumor growth inhibition was observed as low as 0.5 mg/kg dose of AZD9496 in the estrogen-dependent MCF-7 xenograft model, and such effect was accompanied by a dose-dependent decrease in PR protein levels, providing potent antagonist activity. In addition, the combination of AZD9496 with PI3K pathway and CDK4/6 inhibitors resulted in further growth-inhibitory effects when compared with monotherapy alone. Furthermore, the tumor regression was also observed in a long-term estrogen-deprived breast model, in which significant ERα protein downregulation was found [1].
Clinical trial: AZD9496 is currently being evaluated in a phase I clinical trial to assess the PK and safety of different forms and formulations [2].
References:
[1] Weir HM et al. AZD9496: An Oral Estrogen Receptor Inhibitor That Blocks the Growth of ER-Positive and ESR1-Mutant Breast Tumors in Preclinical Models. Cancer Res. 2016 Jun 1;76(11):3307-18.
[2] https://clinicaltrials. gov/ct2/show/NCT02780713 term=AZD9496&rank=2
Cas No. | 1639042-08-2 | SDF | |
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 | ||
Canonical SMILES | O=C(O)/C=C/C1=CC(F)=C([C@H]2N(CC(C)(F)C)[C@H](C)CC3=C2NC4=CC=CC=C34)C(F)=C1 | ||
Formula | C25H25F3N2O2 | M.Wt | 442.47 |
Solubility | DMF: 30 mg/ml,DMSO: 30 mg/ml,Ethanol: 30 mg/ml,Ethanol:PBS (pH 7.2) (1:6): 0.14 mg/mL | Storage | 4°C, protect from light, stored under nitrogen |
General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
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Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. |
Prepare stock solution | |||
1 mg | 5 mg | 10 mg | |
1 mM | 2.26 mL | 11.3002 mL | 22.6004 mL |
5 mM | 0.452 mL | 2.26 mL | 4.5201 mL |
10 mM | 0.226 mL | 1.13 mL | 2.26 mL |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)
Calculation results:
Working concentration: mg/ml;
Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )
Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.
Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.
Average Rating: 5
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