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AT7867 dihydrochloride

Catalog No. T21624 CAS 1431697-86-7

AT7867 dihydrochloride is a potent ATP-competitive inhibitor of Akt1 / Akt2 / Akt3 and p70S6K / PKA kinase with IC 50 s of 32 nM/17 nM/47 nM and 85 nM/20 nM, respectively. AT7867 dihydrochloride is able to induce pharmacodynamic changes and inhibit human tumor xenograft growth.

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AT7867 dihydrochloride Chemical Structure

AT7867 dihydrochloride, CAS 1431697-86-7

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Description	AT7867 dihydrochloride is a potent ATP-competitive inhibitor of Akt1 / Akt2 / Akt3 and p70S6K / PKA kinase with IC 50 s of 32 nM/17 nM/47 nM and 85 nM/20 nM, respectively. AT7867 dihydrochloride is able to induce pharmacodynamic changes and inhibit human tumor xenograft growth.
In vitro	AT7867 ATP-competitive inhibited AKT2 with the Ki of 18nM. AT7867 also shows potent activity against the structurally related AGC kinases p70S6K and PKA, but shows a clear window of selectivity against kinases from other kinase sub-families. In vitro growth inhibition studies show that AT7867 blocks proliferation in a number of human cancer cell lines. AT7867 appears to be most potent at inhibiting proliferation in MES-SA uterine, MDA-MB-468 and MCF-7 breast, and HCT116 and HT29 colon lines (IC 50 values range from 0.9-3 μM), and least effective in the two prostate lines tested (IC 50 values range from 10-12 μM) [1].
In vivo	After oral administration of AT7867 at a dosage of 20 mg/kg, its elimination from plasma mirrors that observed with intravenous (i.v.) administration. Plasma concentrations of AT7867 exceed 0.5 μM for a minimum of 6 hours post-oral dosing at 20 mg/kg. Based on the assumption of linear pharmacokinetics from i.v. administration, the oral bioavailability of AT7867 is estimated at 44%. Consequently, in vivo pharmacodynamic (PD) biomarker studies utilize this model. Subsequent to pharmacokinetic and tolerability assessments, AT7867 doses (90 mg/kg orally or 20 mg/kg intraperitoneally) are given to athymic mice harboring MES-SA tumors, with a focus on monitoring the phosphorylation levels of GSK3β and S6RP within the tumors over time. A significant reduction in the phosphorylation of these two pathway markers is observed at both 2 and 6 hours post-AT7867 administration. By the 24-hour mark, the total levels of GSK3β and S6RP have substantially decreased [1].

Molecular Weight	410.77
Formula	C20H22Cl3N3
CAS No.	1431697-86-7

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Powder: -20°C for 3 years | In solvent: -80°C for 1 year

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Keywords

AT7867 dihydrochloride 1431697-86-7 AT 7867 AT7867 AT 7867 Dihydrochloride AT-7867 Dihydrochloride AT7867 Dihydrochloride AT-7867 inhibitor inhibit

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