Pharmacological profile of KE-758, the main metabolite of the antirheumatic agent KE-298.

Abstract

KE-298(2-acetylthiomethyl-4-(4-methylphenyl)-4-oxobutanoic acid) is a newly developed antirheumatic drug which suppresses the development of arthritis in animal models and has immunomodulatory effects. KE-298 is converted into the deacetylated form, KE-758 (2-mercaptomethyl-4-(4-methylphenyl)-4-oxobutanoic acid), the main serum metabolite in humans, and circulates in peripheral blood following oral administration. The authors compared effects of KE-758 and KE-298 on inflammatory cytokine production from human peripheral blood mononuclear cells and human umbilical vein endothelial cells (HUVEC), interleukin-1 (IL-1)-induced thymocyte proliferation (LAF) activity, adjuvant-induced arthritis in rats and lymphocyte transformation test in mice. KE-758 exhibited almost the same effect as KE-298 both in vitro and in vivo. The authors consider that KE-758 is pharmacologically a metabolite form of KE-298, in vivo.

• Authors: Y Yasuda, T Inoue, K Takeshita
• Journal: Drugs under experimental and clinical research (Drugs Exp Clin Res) Vol. 22 Issue 1 Pg. 1-8 ( 1996) ISSN: 0378-6501 [Print] Switzerland
• PMID: 8839631 (Publication Type: Comparative Study, Journal Article)

Chemical References

• Antirheumatic Agents
• Interleukin-1
• Interleukin-6
• KE 758
• Phenylbutyrates
• Phenylpropionates
• esonarimod

Topics

• Animals
• Antirheumatic Agents (pharmacology)
• Arthritis, Experimental (drug therapy)
• Cell Division
• Endothelium, Vascular (drug effects, metabolism)
• Female
• Humans
• Interleukin-1 (biosynthesis)
• Interleukin-6 (biosynthesis)
• Leukocytes, Mononuclear (drug effects, metabolism)
• Mice
• Phenylbutyrates (pharmacology)
• Phenylpropionates (pharmacology)
• Pregnancy
• Rats
• Rats, Sprague-Dawley
• Thymus Gland (cytology, drug effects)
• Umbilical Veins (drug effects, metabolism)