2020年4月21日 · MK-2206 is an orally active, highly potent and selective allosteric Akt inhibitor, with IC50s of 8, 12, and 65 nM for Akt1, Akt2, and Akt3, respectively. Many breast cancer cell lines, and PIK3CA-mutant and cell lines with PTEN loss are sensitive to MK-2206.

MK-2206 suppressed the Akt phosphorylation that is induced by carboplatin and gemcitabine. In vivo, MK-2206 in combination with these agents exerted significantly more potent tumor inhibitory activities than each agent in the monotherapy setting.

MK-2206 is an organic heterotricyclic compound that is [1,2,4]triazolo [3,4-f] [1,6]naphthyridin-3 (2H)-one substituted by 4- (1-aminocyclobutyl)phenyl and phenyl groups at positions 8 and 9, respectively. It is an allosteric Akt inhibitor.

Akt inhibitor MK2206 binds to and inhibits the activity of Akt in a non-ATP competitive manner, which may result in the inhibition of the PI3K/Akt signaling pathway and tumor cell proliferation …

2019年2月7日 · We evaluated the pan-Akt inhibitor MK-2206 in combination with standard therapy in patients with high-risk early-stage breast cancer. I-SPY 2 is a multicenter, phase II, open-label, adaptively randomized neoadjuvant platform trial that screens experimental therapies and efficiently identifies potential predictive biomarker signatures.

2020年2月9日 · Purpose: The phosphatidylinositol 3-kinase/Akt/mammalian target of rapamycin is a key pathway of survival and therapeutic resistance in breast cancer. We evaluated the pan-Akt inhibitor MK-2206 in combination with standard therapy in …

2011年10月24日 · MK-2206 is a potent, oral allosteric inhibitor of all AKT isoforms with antitumor activity in preclinical models. A phase I study of MK-2206 was conducted to investigate its safety, maximum-tolerated dose (MTD), pharmacokinetics (PKs), pharmacodynamics (PDs), and preliminary antitumor efficacy.

MK-2206 is effective in reducing xenograft growth in models of breast, prostate, nonsmall cell lung, and ovarian cancers (14, 15) and has shown antitumor properties in a small phase I trial, while causing only minor side effects .

2011年12月10日 · MK-2206 is a potent, oral allosteric inhibitor of all AKT isoforms with antitumor activity in preclinical models. A phase I study of MK-2206 was conducted to investigate its safety, maximum-tolerated dose (MTD), pharmacokinetics (PKs), pharmacodynamics (PDs), and preliminary antitumor efficacy.