Nelfinavir Mesylate

• CAT Number: A000146
• CAS Number: 159989-65-8
• Molecular Formula: C32H45N3O4S • CH3SO3H
• Molecular Weight: 663.9
• Purity: ≥95%
• Target: HIV Protease
• Solubility: Soluble in DMSO > 10 mM
• Storage: Store at -20°C
• IUPAC Name: (3S,4aS,8aS)-N-tert-butyl-2-[(2R,3R)-2-hydroxy-3-[(3-hydroxy-2-methylbenzoyl)amino]-4-phenylsulfanylbutyl]-3,4,4a,5,6,7,8,8a-octahydro-1H-isoquinoline-3-carboxamide;methanesulfonic acid
• InChI: InChI=1S/C32H45N3O4S.CH4O3S/c1-21-25(15-10-16-28(21)36)30(38)33-26(20-40-24-13-6-5-7-14-24)29(37)19-35-18-23-12-9-8-11-22(23)17-27(35)31(39)34-32(2,3)4;1-5(2,3)4/h5-7,10,13-16,22-23,26-27,29,36-37H,8-9,11-12,17-20H2,1-4H3,(H,33,38)(H,34,39);1H3,(H,2,3,4)/t22-,23+,26-,27-,29+;/m0./s1
• InChIKey: NQHXCOAXSHGTIA-SKXNDZRYSA-N
• SMILES: CC1=C(C=CC=C1O)C(=O)NC(CSC2=CC=CC=C2)C(CN3CC4CCCCC4CC3C(=O)NC(C)(C)C)O.CS(=O)(=O)O

Nelfinavir Mesylate (CAS 159989-65-8) is an orally active human immunodeficiency virus protease inhibitor. It potently inhibits HIV-1 protease (Ki = 2 nM) in vitro. Also exhibits anti-MERS-CoV activity in Vero cells in vitro (IC50 = 0.08 μM). It demonstrates anti-cancer activity, selectively preventing the growth of HER2-positive breast cancer cells in vitro by inhibiting Hsp90 (IC50 = 3.1 μM).

Overview of Clinical Research

Nelfinavir is a Food and Drug Administration–approved drug that could be repositioned as a cancer therapeutic.

Reference

1.Gills, Joell J., et al. "Nelfinavir, A lead HIV protease inhibitor, is a broad-spectrum, anticancer agent that induces endoplasmic reticulum stress, autophagy, and apoptosis in vitro and in vivo." Clinical cancer research 13.17 (2007): 5183-5194.
2.Ann Pharmacother. 1999 Mar;33(3):325-39. doi: 10.1345/aph.18089.

 

Nelfinavir mesylate: a protease inhibitor.Pai VB(1), Nahata MC.

 

Author information:

(1)College of Pharmacy, Ohio State University, Columbus 43210, USA.

 

OBJECTIVE: To review the clinical pharmacology, pharmacokinetics, efficacy, adverse effects, drug interactions, and dosage guidelines of nelfinavir mesylate.

DATA SOURCE: A MEDLINE search restricted to English-language literature from January 1966 to February 1998 and an extensive review of journals was conducted to prepare this article. MeSH headings included protease inhibitors, nelfinavir mesylate, and AG1343. Abstracts presented at meetings and data submitted to the 

Food and Drug Administration (FDA) were also reviewed.

DATA EXTRACTION: The data on efficacy, pharmacokinetics, adverse effects, and drug interactions were obtained from in vitro studies, as well as open-label and controlled trials.

DATA SYNTHESIS: Nelfinavir inhibits HIV protease enzyme resulting in formation of immature and noninfectious virions. In combination with nucleoside reverse transcriptase inhibitors, nelfinavir is effective in reducing the viral load below the quantifiable limit (< 500 copies/mL) and increasing the mean CD4+ cell count. This antiviral effect is sustained at least over 21 months. The bioavailability of nelfinavir ranges from 20% to 80%, and it increases when nelfinavir is administered with food. Following multiple dosing of nelfinavir 750 mg three times daily, maximum concentration at steady-state was 3-4 

micrograms/mL and minimum concentration was 1-3 micrograms/mL. The elimination half-life for nelfinavir ranges from three to five hours. Nelfinavir is primarily metabolized in the liver by the cytochrome P450 isoenzymes and excreted in the feces. Current dosing recommendations are 750 mg three times daily for adults and adolescents and 20-30 mg/kg/dose three times daily for children aged 2-13 years. Studies of twice-daily regimens in adults are being conducted and are promising. Use of nelfinavir as salvage therapy is also being studied. Some of the commonly reported adverse events of nelfinavir are diarrhea, nausea, vomiting, and abdominal pain.

CONCLUSIONS: Despite the limited published data, the FDA has approved nelfinavir in combination therapy for the treatment of HIV infection. The choice of antiretroviral (ARV) regimens should be made based on the risk of disease progression as indicated by HIV RNA concentrations and CD4+ cell counts, patients' previous ARV experiences and responses, concomitant drug therapy, compliance history, underlying disease states, and adverse reaction history.

 

DOI: 10.1345/aph.18089

PMID: 10200859 [Indexed for MEDLINE]