ChemicalBook CAS DataBase List 1464842-09-8

1464842-09-8

Name	M-8891
CAS	1464842-09-8
Molecular Formula	C20H17F2N3O3
MDL Number	MFCD32710096
Molecular Weight	385.36
MOL File	1464842-09-8.mol

Chemical Properties

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

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.

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%).

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.

Supplier

Related Products

Send Inquriy