M8891 是一种具有口服活性，可逆的且能透过血脑屏障的甲硫氨酸氨基肽酶 2 (MetAP-2) 抑制剂，IC50 为 54 nM，Ki 为 4.33 nM。M8891 不抑制 MetAP-1 (IC 50>10 µM)。M8891 抑制原代内皮细胞以及肿瘤细胞的生长，具有抗血管生成和抗肿瘤活性。
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].
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].
[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.
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