Potential therapeutic indications for synthetic desmuramyl MDP analogue (LK-409).
Synthetic desmuramyl analogues are potentially immunostimulating drugs. Until today a lot of different molecules were constructed, some with interesting augmenting properties, but most of them with unpleasant pyrogenic side effects. LK-409, 7-oxooctanoyl-L-alanyl-D-isoglutamine, synthesised at the Pharmaceutical faculty of Ljubljana, is an apyrogenic derivative with promising immunostimulating activity. LK-409 and the control substance romurtide were tested for more than 50 parameters. All the immune response levels were included in the study; the development and proliferation of stem cells from bone marrow, the natural defence mechanisms with special regard to the function of phagocytic cells, the humoral immune response with special regard to the development of plaque forming cells and the cellular immune response with regard to the proliferating ability of the immune cells and production of regulating and differentiating cytokines, in vitro and in vivo. Results of LK-409 and romurtide activity were sorted in six groups, and evaluated. The analysis shows that LK-409 affects the measured parameters more efficiently than does romurtide. The most pronounced effect was stimulation of the immune response in drug and tumor induced immunosuppression.
Kotnik
V
V
Institute of Microbiology, Medical Faculty Ljubljana, Slovenia.
Stalc
A
A
D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000031:analogs & derivatives / Q000494:pharmacology; D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D000917:Antibody Formation / Q000187:drug effects; D004151:Dipeptides / Q000494:pharmacology*; D006801:Humans; D007111:Immunity, Cellular / Q000187:drug effects; D051379:Mice
D000276:Adjuvants, Immunologic; D004151:Dipeptides; C079179:LK 409; D000119:Acetylmuramyl-Alanyl-Isoglutamine; C036866:romurtide