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INX-08189 + verapamil

Development stage
Unknown
Lead developer
Bristol Myers Squibb
Modality
Orthosteric Ligands → Classical Binding Small Molecules → Small Molecules, Metabolically Activated Prodrugs → Prodrugs/Conditional Activator Small Molecules → Small Molecules, DNA Intercalators/Alkylators → Nucleic Acid-Directed Small Molecules → Small Molecules
Administration
Oral, Intravenous
01

Overview

INX-08189 is a phosphoramidate prodrug of 6-O-methyl-2'-C-methyl guanosine developed as a potent inhibitor of hepatitis C virus (HCV) replication. It acts by inhibiting the HCV NS5B RNA-dependent RNA polymerase and demonstrates high potency in vitro against HCV genotype 1b. Resistance studies show reduced sensitivity with the S282T mutation in NS5B but complete inhibition can still be achieved at higher concentrations. No significant mitochondrial toxicity was observed in preclinical studies[6][8]. Verapamil is a small molecule calcium channel blocker (specifically an L-type calcium channel antagonist) used to treat hypertension, angina pectoris (chest pain), and certain cardiac arrhythmias such as supraventricular tachycardia and atrial fibrillation/flutter. It works by relaxing blood vessels and reducing heart contractility to lower blood pressure and control heart rate[1][2][5]. Brand names for verapamil include Calan, Isoptin SR, Verelan, among others. The combination "INX-08189 + verapamil" does not represent an approved or established fixed-dose pharmaceutical product but rather refers to co-administration of these two agents.

Brand names
CalanCalan SRIsoptin SRVerelanVerelan PM
Other names
6-O-methyl-2'-C-methyl guanosine phosphoramidate prodrugphenylalkylamine calcium channel blocker
02

Targets

LTCC (Voltage-gated calcium channel (L-type))NS5B (Hepatitis C virus non-structural protein 5B (NS5B) RNA-dependent RNA polymerase)

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