      Document 0031
 DOCN  DRG0031
 UNIQUE IDENTIFIER        DRG-0216
 NAME OF SUBSTANCE        SC-52151 [NIAID ACTG 282]
 PROTOCOL ID NUMBERS      NIAID ACTG 282
 SECONDARY SOURCE ID      DRG
 PHARMACOLOGICAL ACTION   MODE OF ACTION: HIV-infected cells produce
                          large polyproteins which are precursors to
                          the individual components of HIV. Protease,
                          which is also produced by HIV-infected cells,
                          cleaves the large precursor proteins, thereby
                          separating the final viral elements (e.g.,
                          p24 and reverse transcriptase) in preparation
                          for viral assembly. If the precursor proteins
                          are not processed by the protease enzyme,
                          nonfunctioning non-infectious virions are
                          formed. The three-dimensional structure of
                          the HIV protease has been fully determined;
                          researchers are therefore able to rationally
                          design compounds (i.e., protease inhibitors)
                          to inhibit it. Selectively inhibited HIV
                          protease in vitro and demonstrated antiviral
                          activity against HIV-1, HIV-2, SIV, and
                          zidovudine-resistant strains of HIV-1 in
                          vitro. After treatment of HIV-infected CEM
                          cells with SC-52151, the virus core of
                          infectious extracellular virus particles was
                          absent. The manufacturer has announced that
                          development on their two protease inhibitors,
                          SC-52151 & SC-55389A, has ceased. [NIAID ACTG
                          282] [AmFAR Tx Dir Jan 1995;7(4)]
 DISEASES STUDIED/TREATED Primary HIV infection [NIAID ACTG 282]
 CLASSIFICATION CODE      Protease inhibitor [NIAID ACTG 282]
 CLASSIFICATION CODE      Antiretroviral [NIAID ACTG 282]
 CONTRAINDICATIONS        Contraindicated in pregnant or nursing women,
                          since safety has not been determined. [NIAID
                          ACTG 282]
 CHEMICAL/PHYSICAL DATA   DRUG DESCRIPTION: Urea-based peptidomimetic
                          [NIAID ACTG 282]
 SUBSTANCE DELIVERY DATA  DOSAGE FORM: 175 ml amber glass bottles of
                          elixir or SEDDS (self-emulsifying drug
                          delivery system) formulation. [NIAID ACTG
                          282]
 SUBSTANCE DELIVERY DATA  MODE OF DELIVERY: Oral. [NIAID ACTG 282]
 SUBSTANCE DELIVERY DATA  STORAGE: Store at room temperature. [NIAID
                          ACTG 282]
 MANUFACTURERS            G D Searle & Co
 REFERENCES               Fischl MA, Richman DD, Flexner C, Meehan P,
                          Para MF, Haubrich R, Cook J, Wood K, Karim A.
                          Phase I study of two formulations and dose
                          schedules of SC-521151, a protease inhibitor.
                          Natl Conf Hum Retroviruses Relat Infect
                          (2nd). 1995 Jan 29-Feb 2;:88.
 REFERENCES               Getman DP, De Crescenzo GA, Heintz RM, Reed
                          KL, Talley JJ, Bryant ML, Clare M, Houseman
                          KA, Marr JJ, Mueller RA, et al. Discovery of
                          a novel class of potent HIV-1 protease
                          inhibitors containing the
                          (R)-(hydroxyethyl)urea isostere. J Med Chem.
                          1993 Jan 22;36(2):288-91.
 ENTRY MONTH              9408
 LAST REVISION DATE       960503
 

SOURCE: National Library of Medicine, Bethesda, MD.  Distributed by AEGIS.
