| Chemical Properties | Back Directory | [Boiling point ]
755.6±60.0 °C(Predicted) | [density ]
1.496±0.06 g/cm3(Predicted) | [form ]
Solid | [pka]
11.51±0.20(Predicted) | [color ]
Off-white to light yellow |
| Hazard Information | Back Directory | [Description]
M8891 is a potent and orally active methionine aminopeptidase 2 inhibitor with potential antiangiogenic and antineoplastic activities. Upon administration, MetAP2 inhibitor M8891 inhibits MetAP2 aminopeptidase activity and impairs protein synthesis, which may lead to a decrease in endothelial cell proliferation. Decreased proliferation of endothelial cells results in reductions of both angiogenesis and the growth and spread of solid tumors that are dependent on new blood vessel formation. MetAP2, a metallopeptidase, is involved in promoting protein synthesis and endothelial cell proliferation. | [Uses]
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]. | [in vivo]
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.
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| 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%).
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| [References]
[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. DOI:10.1021/acs.jmedchem.9b01070
[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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