Indinavir sulfate ethanolate

Indinavir sulfate ethanolate (MK-639 ethanolate) is an orally active and selective HIV-1 protease inhibitor with a Ki of 0.54 nM for PR. Indinavir sulfate ethanolate exhibits anticancer activity by inhibiting the activation of MMPs-2 hydrolysis, anti-angiogenesis and inducing apoptosis. Indinavir sulfate ethanolate is also a SARS-CoV 3CLpro inhibitor[1][2][3][4].

Signaling Pathways >> Apoptosis >> Apoptosis

Research Areas >> Cancer

Signaling Pathways >> Anti-infection >> HIV

Research Areas >> Infection

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

Signaling Pathways >> Metabolic Enzyme/Protease >> MMP

Signaling Pathways >> Metabolic Enzyme/Protease >> HIV Protease

HIV-1

MMP-2

Indinavir sulfate ethanolate (0-50 µM; 18 h) blocks lymphocyte cell cycle in G0/G1 phase in PBMCs cells and impairs lymphoproliferative responses[1]. Indinavir sulfate ethanolate (40 µM-40 nM; 5 days) inhibits cell invasion and (40 µM-40 nM; 48 h) MMPs-2 activation of the Huh7 and SK-HEP-1 hepatocarcinoma cells in vitro[2]. Cell Viability Assay[1] Cell Line: PBMCs (from healthy and HIV-infected volunteers) Concentration: 0-50 µM Incubation Time: 18 h (pretreatment; stimulation with anti-CD3 for an additional 48 hours) Result: Blocked anti-CD3-induced cell-cycle progression in a dose-dependent manner. Resulted in dose-dependent reduction of lymphoproliferative responses. Cell Invasion Assay[2] Cell Line: Huh7 and SK-HEP-1 cells Concentration: 40 µM-40 nM Incubation Time: 5 days Result: Reduced ability to invade an in vitro constituted extracellular matrix for both cell lines treated compared with the untreated cells. Western Blot Analysis[2] Cell Line: Huh7 and SK-HEP-1 cells Concentration: 40 µM-40 nM Incubation Time: 48 h Result: Blocked the conversion of latent MMP-2 to its 62/64-kDa active form.

Indinavir sulfate ethanolate (70 mg/kg; i.g.; once a day for 3 weeks) inhibits the growth of hepatocarcinoma cells in vivo[2]. Animal Model: Nude mice(s.c. into Huh7 and SK-HEP-1 cells)[2]. Dosage: 70 mg/kg Administration: Oral gavage; once a day for 3 weeks Result: Delaied the growth of s.c. implanted hepatocarcinoma xenografts in nude mice compared with placebo.

[1]. Chavan S, et al. The HIV protease inhibitor Indinavir inhibits cell-cycle progression in vitro in lymphocytes of HIV-infected and uninfected individuals. Blood. 2001 Jul 15;98(2):383-9.

[2]. Esposito V, et al. Evaluation of antitumoral properties of the protease inhibitor indinavir in a murine model of hepatocarcinoma. Clin Cancer Res. 2006 Apr 15;12(8):2634-9.

[3]. Liu F, et al. Kinetic, stability, and structural changes in high-resolution crystal structures of HIV-1 protease with drug-resistant mutations L24I, I50V, and G73S. J Mol Biol. 2005 Dec 9;354(4):789-800.

[4]. Hall DC Jr, et al. A search for medications to treat COVID-19 via in silico molecular docking models of the SARS-CoV-2 spike glycoprotein and 3CL protease. Travel Med Infect Dis. 2020 May-Jun;35:101646.