Studies on the effect of CL 306,293, a substituted quinoline carboxylic acid, on the clinical disease induced in mice with LP-BM5 virus.
CL 306,293, a substituted quinoline carboxylic acid, is a potent inhibitor of dihydroorotic acid dehydrogenase, an enzyme essential for the biosynthesis of pyrimidines. In mammalian cell culture, the agent exhibits antiproliferative properties that can be reversed by the addition of uridine. CL 306,293 inhibits the development of the clinical disease in a murine model of immunodeficiency induced by a mixture of LP-BM5 retroviruses. In infected mice, the agent prevents the development of hypergammaglobulinemia, lymphadenopathy, splenomegaly and induction of an IL-2 deficiency. The CD4/CD8 ratio and the number of B cells in the lymph nodes are decreased if the infected animals are treated with CL 306,293. CL 306,293 was more efficacious and potent than 3'-azido-3'-deoxythymidine. The beneficial effects of CL 306,293 observed in this model are most probably related to its antiproliferative properties.
Oncology, and Immunology Research Section, American Cyanamid Company, Lederle Laboratories, Pearl River, NY 10965.
J W
JW
Scott
S Q
SQ
DeJoy
R
R
Jeyaseelan
D W
DW
Powell
C
C
Raventos-Suarez
B
B
O'Hara
M M
MM
Wick
A L
AL
Oronsky
S S
SS
Kerwar
D000386:AIDS-Related Complex; D000634:Aminoquinolines / Q000627:therapeutic use* / Q000633:toxicity; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D001402:B-Lymphocytes / Q000502:physiology; D001713:Biphenyl Compounds / Q000627:therapeutic use* / Q000633:toxicity; D016516:CD4-CD8 Ratio; D002478:Cells, Cultured; D004081:Dihydroorotate Oxidase / Q000037:antagonists & inhibitors*; D005347:Fibroblasts / Q000187:drug effects; D006942:Hypergammaglobulinemia; D007075:Immunoglobulin M / Q000032:analysis; D007376:Interleukin-2 / Q000172:deficiency; D051379:Mice; D008810:Mice, Inbred C57BL; D016183:Murine Acquired Immunodeficiency Syndrome / Q000188:drug therapy* / Q000201:enzymology; D012008:Recurrence; D013163:Splenomegaly; D015215:Zidovudine / Q000627:therapeutic use
D000634:Aminoquinolines; D000914:Antibodies, Viral; D001713:Biphenyl Compounds; D007075:Immunoglobulin M; D007376:Interleukin-2; C071309:3-amino-2-(1,1'-biphenyl)-4-yl-6-fluoro-4-quinolinecarboxylic acid; D015215:Zidovudine; D004081:Dihydroorotate Oxidase