MK-2206 dihydrochloride,1032350-13-2,IC-0198257

MK-2206 dihydrochloride is an orally active allosteric Akt inhibitor used in treatment of solid tumors.[1]

IIn vitro experiment it shown that MK-2206 is equally potent toward purified recombinant human Akt1 and Akt2 enzyme with IC50 of 5 nmol/L and 12 nmol/L, respectively; and approximately 5-fold less potent against human Akt3 (IC50, 65 nmol/L). MK-2206 potently inhibited the cell growth of Ras wild-type (WT) cell lines (A431, HCC827, and NCI-H292 with IC50s of 5.5, 4.3, and 5.2 μmol/L, respectively. The combination of 2.5 μmol/L erlotinib and 3 μmol/L MK-2206 or higher obviously activated the caspase.[1] In vitro, Akt inhibitor (MK 2206 dihydrochloride, 2.5 nM) reduces the effects of anti-microRNA-320a on the apoptosis of MDA-MB-231 cells.[2] In vitro, treatment with 0.1 and 1 μM for 48 h MK-2206 reduced the expression p-Akt in all pancreatic cancer cell lines suggesting that MK-2206 inhibited Akt phosphorylation in pancreatic cancer cells.[3] In vitro the colony formation assay confirmed that 1 μM of MK-2206 significantly inhibited the proliferation of SGC-7901 cells.[4]

In vivo test displayed it that treatment with 120 mg/kg MK-2206 orally 2 hours after erlotinib (50 mg/kg), and tumors were isolated 14 hours after erlotinib administration to verify the inhibition of phospho-Akt for the PI3K pathway and phospho-Erk for the Ras/Erk pathway. In vivo efficacy studies it demonstrated that the antitumor efficacy of MK-2206 with once a week at 360 mg/kg intermittently dosing was quite similar to the efficacy of three times a week at 120 mg/kg dosing when MK-2206 was combined with erlotinib.[1].

MK-2206双盐酸盐是一种口服活性的变构Akt抑制剂，用于治疗实体肿瘤。