      Document 0045
 DOCN  DRG0045
 UNIQUE IDENTIFIER        DRG-0202
 NAME OF SUBSTANCE        MDL 28574 [CHEMLINE]
 REGISTRY NUMBER          121104-96-9
 STANDARD CHEMICAL NAME   Butanoic acid,
                          octahydro-1,7,8-trihydroxy-6-indolizinyl
                          ester,
                          (1S-(1alpha,6beta,7alpha,8beta,8abeta))-[CHEM-
                          LINE]
 SYNONYMS                 MDL 28,574 [MeSH]
 SYNONYMS                 MDL-28574 [MeSH]
 SYNONYMS                 6-O-butanoylcastanospermine [MeSH]
 SYNONYMS                 MDL 28574A (hydrochloride salt) [FDA 221B]
 PROTOCOL ID NUMBERS      FDA 221A
 PROTOCOL ID NUMBERS      FDA 221B
 PROTOCOL ID NUMBERS      FDA 221C
 SECONDARY SOURCE ID      DRG
 PHARMACOLOGICAL ACTION   MODE OF ACTION: Demonstrates inhibitory
                          effect on glucosidases and has antiviral
                          activity against HIV-1 and against Moloney
                          murine leukemia virus (MOLV). In previous
                          studies, MDL 28574 had an IC50 of 0.3 mcg/ml
                          against HIV-induced syncytial formation in
                          HeLa T4+ cells and an IC50 of 0.15 mcg/ml
                          against productive infection in JM cells
                          infected with HIV-1. In both cases, MDL 28574
                          was more potent than castanospermine. The
                          IC50 was 0.05 mcg/ml against MOLV. MDL 28574
                          also showed equivalent activity to AZT and
                          was more potent than castanospermine in
                          inhibiting FLV-induced splenomegaly in mice.
                          [Ann N Y Acad Sci 1990;616] [Biochem Biophys
                          Res Commun 1995 Mar 8;208(1)]
 DISEASES STUDIED/TREATED Primary HIV infection [FDA 221A]
 CLASSIFICATION CODE      Antiretroviral [Ann N Y Acad Sci 1990;616]
 CLASSIFICATION CODE      Alpha glucosidase I inhibitor [Ann N Y Acad
                          Sci 1990;616]
 CHEMICAL/PHYSICAL DATA   DRUG DESCRIPTION: Analogue of the glucosidase
                          I inhibitor, castanospermine [Ann N Y Acad
                          Sci 1990;616] [Glycobiol 1995 Mar;5(2)]
 CHEMICAL/PHYSICAL DATA   MOLECULAR FORMULA: C12H21NO5 [CHEMLINE]
 SUBSTANCE DELIVERY DATA  DOSAGE FORM: Solution. [FDA 221A]
 SUBSTANCE DELIVERY DATA  MODE OF DELIVERY: Oral. [FDA 221A]
 MANUFACTURERS            Marion Merrell Dow Inc
 REFERENCES               Brennan TM, Taylor DL, Bridges CG, Leyda JP,
                          Tyms AS. The inhibition of human
                          immunodeficiency virus type 1 in vitro by a
                          non-nucleoside reverse transcriptase
                          inhibitor MKC-442, alone and in combination
                          with other anti-HIV compounds. Antiviral Res.
                          1995 Mar;26(2):173-87.
 REFERENCES               Bridges CG, Taylor DL, Kang MS, Brennan TM,
                          Tyms AS. Treatment with the alpha-glucosidase
                          I inhibitor 6-O-butanoyl castanospermine
                          reduces the detection of LFA-1 (CD18/CD11a)
                          by monoclonal antibodies. Glycobiology. 1995
                          Mar;5(2):243-7.
 REFERENCES               Bridges CG, Ahmed SP, Kang MS, Nash RJ,
                          Porter EA, Tyms AS. The effect of oral
                          treatment with 6-O-butanoyl castanospermine
                          (MDL 28,574) in the murine zosteriform model
                          of HSV-1 infection. Glycobiology 1995
                          March;5(2):249-53.
 REFERENCES               Ahmed SP, Nash RJ, Bridges CG, Taylor DL,
                          Kang MS, Porter EA, Tyms AS. Antiviral
                          activity and metabolism of the
                          castanospermine derivative MDL 28,574, in
                          cells infected with herpes simplex virus type
                          2. Biochem Biophys Res Commun 1995 Mar
                          8;208(1):267-73.
 REFERENCES               Bridges CG, Brennan TM, Taylor DL, McPherson
                          M, Tyms AS. The prevention of cell adhesion
                          and the cell-to-cell spread of HIV-1 in vitro
                          by the alpha-glucosidase 1 inhibitor,
                          6-O-butanoyl castanospermine (MDL 28574).
                          Antiviral Res. 1994 Oct;25(2):169-75.
 REFERENCES               Taylor DL, Kang MS, Brennan TM, Bridges CG,
                          Sunkara PS, Tyms AS. Inhibition of
                          alpha-glucosidase I of the
                          glycoprotein-processing enzymes by
                          6-O-butanoyl castanospermine (MDL 28,574) and
                          its consequences in human immunodeficiency
                          virus-infected T cells. Antimicrob Agents
                          Chemother. 1994 Aug;38(8):1780-7.
 REFERENCES               Taylor DL, Sundara PS, Liu PS, Kang MS,
                          Bowlin TL, Tyms AS.
                          6-O-butanoylcastanospermine (MDL 28,574)
                          inhibits glycoprotein processing and the
                          growth of HIVs. AIDS. 1991 Jun;5(6):693-8.
 REFERENCES               Sankara PS, Kang MS, Bowlin TL, Liu PS, Tyms
                          AS, Sjoerdsma A. Inhibition of glycoprotein
                          processing and HIV replication by
                          castanospermine analogues. Ann NY Acad Sci.
                          1990;616:90-6.
 ENTRY MONTH              9403
 LAST REVISION DATE       960417
 

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