product name AZD8835
Description: AZD8835 is a orally bioavailable inhibitor of the class I (PI3K) catalytic subunit alpha (PIK3CA), with potential antineoplastic activity. PI3K alpha inhibitor AZD8835 selectively binds to and inhibits PIK3CA and its mutated forms, in the PI3K/Akt (protein kinase B)/mammalian target of rapamycin (mTOR) pathway. This results in both apoptosis and growth inhibition in PIK3CA-expressing tumor cells. By specifically targeting PIK3CA, this agent may be more efficacious and less toxic than pan-PI3K inhibitors. Dysregulation of the PI3K/Akt/mTOR pathway is often found in solid tumors and results in the promotion of tumor cell growth, survival, and resistance to chemo- and radio-therapy.
References: Mol Cancer Ther. 2016 May;15(5):877-89; Bioorg Med Chem Lett. 2015;25(22):5155-62; Curr Opin Pharmacol. 2015;23:82-91.
469.54
Formula
C22H31N9O3
CAS No.
1620576-64-8
Storage
-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)
DMSO: 93 mg/mL (198.1 mM)
Water: <1 mg/mL
Ethanol: <1 mg/mL
Solubility (In vivo)
Synonyms
other peoduct :
| In Vitro |
In vitro activity: AZD8835 is a potent inhibitor of PI3Kα (wild type, E545K and H1047R mutations) and PI3Kδ with excellent selectivity vs. PI3Kβ, PI3Kγ and an excellent general kinase selectivity. AZD8835 is a potent inhibitor of p-Akt in cells sensitive to PI3Kα inhibition (IC50=0.057 μM in PIK3CA mutant human breast ductal carcinoma BT474 cell line) and in cells sensitive to PI3Kδ inhibition (IC50=0.049 μM in JeKo-1 B cell line), but not to cells sensitive to PI3Kβ inhibition (IC50=3.5 μM in PTEN null breast adenocarcinoma MDA-MB-468 cell line) or PI3Kγ inhibition (IC50=0.53 μM in monocytic RAW264 cell line). Kinase Assay: Cell Assay: BT474, MCF7, or T47D cells are seeded in 384-well plates at a density of 500 to 2,000 cells per well and incubated overnight. Cells are dosed with compound(s) and cell confluency is measured at 4-hour intervals over several days. |
|---|---|
| In Vivo | AZD8835 has antitumor efficacy in corresponding breast cancer xenograft models when dosed continuously and displays high metabolic stability and suitable physical properties for oral administration. |
| Animal model | CD1 mice |
| Formulation & Dosage | Prepared as a suspension in HPMC/Tween [0.5% hydroxypropyl methocellulose (Methocel (Colocorn))/0.1% Polysorbate 80]; 0.1 mL/10 g mouse; Oral administration |
| References | Mol Cancer Ther. 2016 May;15(5):877-89; Bioorg Med Chem Lett. 2015 Nov 15;25(22):5155-62; Curr Opin Pharmacol. 2015 Aug;23:82-91. |
