Amprenavir

Amprenavir (original brand name Agenerase, GlaxoSmithKline) is a protease inhibitor used to treat HIV infection. It was approved by the Food and Drug Administration on April 15, 1999, for twice-a-day dosing instead of needing to be taken every eight hours. The convenient dosing came at a price, as the dose required is 1,200 mg, delivered in 8 (eight) very large 150 mg gel capsules or 24 (twenty-four) 50 mg gel capsules twice daily.[1]

Amprenavir
Clinical data
Trade namesAgenerase
AHFS/Drugs.comMonograph
MedlinePlusa699051
License data
Pregnancy
category
  • US: C (Risk not ruled out)
    Routes of
    administration    		Oral (capsules)
    ATC code
    Legal status
    Legal status
    • In general: ℞ (Prescription only)
    Pharmacokinetic data
    Protein binding90%
    MetabolismHepatic
    Elimination half-life7.1–10.6 hours
    Excretion<3% renal
    Identifiers
    CAS Number
    PubChem CID
    DrugBank
    ChemSpider
    UNII
    KEGG
    ChEBI
    ChEMBL
    NIAID ChemDB
    ECHA InfoCard100.262.589
    Chemical and physical data
    FormulaC25H35N3O6S
    Molar mass505.628 g/mol g·mol−1
    3D model (JSmol)
      (verify)

    It was patented in 1992 and approved for medical use in 1999.[2] Production of amprenavir was discontinued by the manufacturer on December 31, 2004; a prodrug version (fosamprenavir), is available.

    Background

    Research aimed at development of renin inhibitors as potential antihypertensive agents had led to the discovery of compounds that blocked the action of this peptide cleaving enzyme. The amino acid sequence cleaved by renin was found to be fortuitously the same as that required to produce the HIV peptide coat. Structure–activity studies on renin inhibitors proved to be of great value for developing HIV protease inhibitors. Incorporation of an amino alcohol moiety proved crucial to inhibitory activity for many of these agents. This unit is closely related to the one found in the statine, an unusual amino acid that forms part of the pepstatin, a fermentation product that inhibits protease enzymes.

    HIV-1 protease dimer with amprenavir (sticks) bound in the active site. PDB entry 3nu3[3]

    References
    1. "Agenerase (amprenavir) Capsules. Full Prescribing Information. Section Dosage and Administration" (PDF). US Food and Drug Administration. GlaxoSmithKline and Vertex Pharmaceuticals Inc. Retrieved 29 November 2015.
    2. Fischer, Jnos; Ganellin, C. Robin (2006). Analogue-based Drug Discovery. John Wiley & Sons. p. 509. ISBN 9783527607495.
    3. Shen, C. H.; Wang, Y. F.; Kovalevsky, A. Y.; Harrison, R. W.; Weber, I. T. (2010). "Amprenavir complexes with HIV-1 protease and its drug-resistant mutants altering hydrophobic clusters". FEBS Journal. 277 (18): 3699–3714. doi:10.1111/j.1742-4658.2010.07771.x. PMC 2975871. PMID 20695887.
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