      Document 0070
 DOCN  DRG0070
 UNIQUE IDENTIFIER        DRG-0177
 NAME OF SUBSTANCE        Threonyl muramyl dipeptide [CHEMLINE]
 REGISTRY NUMBER          66112-59-2
 STANDARD CHEMICAL NAME   D-alpha-glutamine,
                          N(2)-(N-(N-acetylmuramoyl)-L-threonyl)-
                          [CHEMLINE]
 SYNONYMS                 Threonyl MDP [NIAID VEU 015]
 SYNONYMS                 MDP [NIAID VEU 015]
 SYNONYMS                 RS-37449 [CHEMLINE]
 SYNONYMS                 Temurtide [NIAID VEU 015]
 SYNONYMS                 N-acetylmuramyl-L-threonyl-D-isoglutamine
                          [NIAID VEU 015]
 SYNONYMS                 ThrMDP [Eur J Immunol 1992 Sep;22(9)]
 PROTOCOL ID NUMBERS      NIAID VEU 015
 SECONDARY SOURCE ID      DRG
 PHARMACOLOGICAL ACTION   MODE OF ACTION: The mechanisms in which
                          adjuvants augment vaccine immunogenicity may
                          include 1) the prolongation of antigen
                          exposure to antigen-presenting cells by the
                          creation of a depot at the site of injection,
                          2) the activation of antigen-presenting
                          cells, such as monocytes or macrophages, to
                          release cytokines that can promote T-cell
                          help for B cell and CTL response, 3) the
                          introduction of antigen into the MHC Class I
                          processing pathway. As a result, the adjuvant
                          may induce a more favorable antibody response
                          with high titers, which appear earlier in the
                          course of immunization and persist over time,
                          as well as increase memory responses and CD8+
                          MHC Class I-restricted CTL. Among 130 analogs
                          of muramyl dipeptides tested on animals,
                          threonyl muramyl dipeptide showed the
                          greatest separation of potency as an adjuvant
                          from potency in the production of
                          side-effects. [NIAID VEU 015] [Mol Immunol
                          1991 Mar;28(3)] [Ann NY Acad Sci 1995 May
                          31;754]
 DISEASES STUDIED/TREATED Primary HIV infection: as a vaccine adjuvant
                          for the enhancement of the immune response
                          [NIAID VEU 015]
 CLASSIFICATION CODE      Adjuvant [Ann NY Acad Sci 1995 May 31;754]
 CLASSIFICATION CODE      Immunostimulant [NIAID VEU 015]
 CHEMICAL/PHYSICAL DATA   DRUG DESCRIPTION: A synthetic muramyl
                          dipeptide analog [Semin Immunol 1990
                          Sep;2(5)]
 CHEMICAL/PHYSICAL DATA   MOLECULAR FORMULA: C2OH34N4O12 [CHEMLINE]
 SUBSTANCE DELIVERY DATA  DOSAGE FORM: Vial containing 0.5 ml. [NIAID
                          VEU 015]
 SUBSTANCE DELIVERY DATA  MODE OF DELIVERY: Intramuscular injection.
                          [NIAID VEU 015]
 SUBSTANCE DELIVERY DATA  STORAGE INSTRUCTIONS: Vials should be stored
                          at 5 C. [NIAID VEU 015]
 MANUFACTURERS            The BIOCINE Company
 REFERENCES               Hjorth RN, Bonde GM, Piner ED, Goldberg KM,
                          Levner MH, Hung PP. Relevance of the
                          guinea-pig necrotic inflammation footpad
                          reaction to safety concerns with MDP-based
                          adjuvants. Vaccine 1994 Jun;12(8):687-90.
 REFERENCES               Gupta RK, Relyveld EH, Lindblad EB, Bizzini
                          B, Ben-Efraim S, Gupta CK. Adjuvants--a
                          balance between toxicity and adjuvanticity.
                          Vaccine. 1993;11(3):293-306.
 REFERENCES               Osterhaus A, de Vries P, Morein B, Akerblom
                          L, Heeney J. Comparison of protection
                          afforded by whole virus ISCOM versus MDP
                          adjuvanted formalin-inactivated SIV vaccines
                          from IV cell-free or cell-associated
                          homologous challenge. AIDS Res Hum
                          Retroviruses. 1992 Aug;8(8):1507-10.
 REFERENCES               Ivins BE, Welkos SL, Little SF, Crumrine MH,
                          Nelson GO. Immunization against anthrax with
                          Bacillus anthracis protective antigen
                          combined with adjuvants. Infect Immun. 1992
                          Feb;60(2):662-8.
 REFERENCES               Ewasyshyn M, Caplan B, Bonneau AM, Scollard
                          N, Graham S, Usman S, Klein M. Comparative
                          analysis of the immunostimulatory properties
                          of different adjuvants on the immunogenicity
                          of a prototype parainfluenza virus type 3
                          subunit vaccine. Vaccine. 1992;10(6):412-20.
 REFERENCES               Allison AC, Byars NE. Immunological
                          adjuvants: desirable properties and
                          side-effects. Mol Immunol. 1991
                          Mar;28(3):279-84.
 REFERENCES               Allison AC, Byars NE. Adjuvant formulations
                          and their mode of action. Semin Immunol. 1990
                          Sep;2(5):369-74.
 REFERENCES               Murphey-Corb M, Martin LN, Davison-Fairburn
                          B, Montelaro RC, Miller M, West M, Ohkawa S,
                          Baskin GB, Zhang JY, Putney SD, et al. A
                          formalin-inactivated whole SIV vaccine
                          confers protection in macaques. Science. 1989
                          Dec 8;246(4935):1293-7.
 ENTRY MONTH              9306
 LAST REVISION DATE       960405
 

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