M8891

M8891 is an orally active, reversible and brain penetrant Methionine Aminopeptidase-2 (MetAP-2) inhibitor with an IC50 of 54 nM and a Ki of 4.33 nM. M8891 does not inhibit MetAP-1 (IC50>10 µM)[1]. M8891 inhibits growth of primary endothelial cells as well as tumor cells and demonstrates antiangiogenic and antitumoral activity[2].

Research Areas >> Cancer

Signaling Pathways >> Others >> Others

IC50: 54 nM (MetAP-2)[1] Ki: 4.33 nM (MetAP-2)[1]

M8891 has an IC50 of 20 nM for HUVEC proliferation[1].

M8891 (po; 20 mg/kg; once a day for 14 days) exhibits strong tumor growth inhibition[1]. M8891 (iv; 0.2 mg/kg) shows low clearance (CL ~0.03-0.4 L/h/kg corresponding to ~1-6% of the liver blood-flow), small to medium volume of distribution (Vss ~0.23-1.3 L/kg), and medium to high oral bioavailability (F ~40-80%)[1]. Animal Model: Female CD-1 nude mice aged 6-7 weeks with human U87-MG glioblastoma[1] Dosage: 20 mg/kg Administration: Po; once a day for 14 days Result: Exhibited strong tumor growth inhibition. Animal Model: Rat, dog and monkey[1] Dosage: 0.2 mg/kg (Pharmacokinetic Analysis) Administration: IV Result: Showed low clearance (CL ~0.03-0.4 L/h/kg corresponding to ~1-6% of the liver blood-flow), small to medium volume of distribution (Vss ~0.23-1.3 L/kg), and medium to high oral bioavailability (F ~40-80%).

[1]. Heinrich T, et al. Identification of Methionine Aminopeptidase-2 (MetAP-2) Inhibitor M8891: A Clinical Compound for the Treatment of Cancer. J Med Chem. 2019 Dec 26;62(24):11119-11134.

[2]. Manja Friese-Hamim, et al. Abstract 3075: Antitumor activity of M8891, a potent and reversible inhibitor of methionine aminopeptidase 2.