MI-1851

MI-1851 is a potent furin inhibitor. MI-1851 prevents the proteolytic processing of the S protein of SARS-CoV-2 by endogenous flavoprotease in HEK293 cells. MI-185 has antiviral activity[1][2].

Research Areas >> Infection

Signaling Pathways >> Anti-infection >> SARS-CoV

MI-1851 (0-100 μM, 2h, 24 h) does not affect PHH cells viability, and extracellular hydrogen peroxide production even at 100 μM but reduces CYP3A4 isoenzyme activity in PHH cells in a dose-dependent manner[1]. MI-1851 (10-50 μM, 72 h) strongly inhibits the spread of SARS-CoV-2 and its proliferation in Calu-3 cells even at a low dose of 10 μM, which reduces the virus titer by 30 to 190-fold[2]. MI-1851 (compound 8) (0.5-16 μM, 48 h) inhibits DENV-2 and WNV replication with the EC50 values of 1.50 μM and 1.46 μM, respectively in huh-7 cells[3].

Animal Model: Rats[3] Dosage: 2.5 mg/kg Administration: Intravenous injection; once Result: The pharmacokinetic parameters of MI-1851 (compound 8) Parameter MI-1851 (compound 8) t1/2 1.6 h total body clearance 273 mL/(h•kg) Cmax 3156 ng/mL

[1]. Erzsébet Pászti-Gere, et al. In vitro characterization of the furin inhibitor MI-1851: Albumin binding, interaction with cytochrome P450 enzymes and cytotoxicity. Biomed Pharmacother. 2022 Jul;151:113124.

[2]. Dorothea Bestle, et al. TMPRSS2 and furin are both essential for proteolytic activation of SARS-CoV-2 in human airway cells. Life Sci Alliance. 2020 Jul 23;3(9):e202000786.

[3]. Thuy Van Lam van, et al. The Basicity Makes the Difference: Improved Canavanine-Derived Inhibitors of the Proprotein Convertase Furin. ACS Med Chem Lett. 2021 Feb 9;12(3):426-432.