Studies on the effect of CL 306,293, a substituted quinoline carboxylic acid, on the clinical disease induced in mice with LP-BM5 virus

Jeffery W. Scott, Susan Quinn DeJoy, Robert Jeyaseelan, Dennis W. Powell, Carmen Raventos-Suarez, Bryan O'Hara, Michael M. Wick, Arnold L. Oronsky, S. S. Kerwar

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)71-81
Number of pages11
JournalAntiviral Research
Volume20
Issue number1
DOIs
StatePublished - Jan 1993

Keywords

  • AIDS
  • Antimetabolite
  • Antiproliferative
  • Azidothymidine
  • CL 306,293
  • Dihydroorotic acid dehydrogenase inhibitor
  • LP-BM5 retrovirus
  • MAIDS
  • MuLV

ASJC Scopus subject areas

  • Pharmacology
  • Virology

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    Scott, J. W., DeJoy, S. Q., Jeyaseelan, R., Powell, D. W., Raventos-Suarez, C., O'Hara, B., Wick, M. M., Oronsky, A. L., & Kerwar, S. S. (1993). Studies on the effect of CL 306,293, a substituted quinoline carboxylic acid, on the clinical disease induced in mice with LP-BM5 virus. Antiviral Research, 20(1), 71-81. https://doi.org/10.1016/0166-3542(93)90060-V