Miransertib hydrochloride (ARQ-092 hydrochloride) is a powerful, orally bioavailable, selective, and allosteric inhibitor of Akt. It exhibits an inhibitory concentration (IC50) of 2.7 nM, 14 nM, and 8.1 nM against Akt1, Akt2, and Akt3, respectively. In addition to its Akt inhibitory activity, Miransertib hydrochloride also demonstrates significant potency as an inhibitor of the AKT1-E17K mutant protein. This compound shows promise in research related to PI3K/AKT-driven tumors and Proteus syndrome. Furthermore, Miransertib hydrochloride displays efficacy against Leishmania [1, 2].

In a large panel of cell lines derived from various tumor types, Miransertib (ARQ-092; Compound 21a) exhibits potent anti-proliferative activity in cell lines containing PIK3CA/PIK3R1 mutations compared to those with wild-type (wt) PIK3CA/PIK3R1 or PTEN loss. Miransertib exhibits excellent inhibition of p-Akt (S473) and p-Akt (T308) in both AN3CA and A2780 cells. The inhibition of the downstream protein p-PRAS40 (T246) is observed with Miransertib (IC 50 =0.31 μM) [1]. Miransertib is markedly effective against intracellular amastigotes of L. donovani or L. amazonensis -infected macrophages. Miransertib also enhances mTOR dependent autophagy in Leishmania -infected macrophages [2]

Miransertib (ARQ-092; Compound 21a) exhibits good absolute oral bioavailability in rats (5 mg/kg) and monkeys (10 mg/kg) with F values of 62% and 49%, respectively. The half-life is longer in rats compared to monkeys with t 1/2 values of 17 h in rats versus 7 h in monkeys. The C max is 198 ng/mL and 258 ng/mL and the AUC inf was 5496 h ng/mL and 2960 h ng/mL in rats and monkeys, respectively [1]. Miransertib (ARQ-092; Compound 21a) inhibits tumor growth in a human xenograft mouse model of endometrial adenocarcinoma [1].