Pharmacological profile of KE-758, the main metabolite of the antirheumatic agent KE-298.
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.
Yasuda
Y
Y
Medical Research Laboratories, Taisho Pharmaceutical Company, Saitama, Japan.
Inoue
T
T
Takeshita
K
K
D000818:Animals; D018501:Antirheumatic Agents / Q000494:pharmacology*; D001169:Arthritis, Experimental / Q000188:drug therapy*; D002455:Cell Division; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D006801:Humans; D007375:Interleukin-1 / Q000096:biosynthesis; D015850:Interleukin-6 / Q000096:biosynthesis; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D010654:Phenylbutyrates / Q000494:pharmacology*; D010666:Phenylpropionates / Q000494:pharmacology*; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D013950:Thymus Gland / Q000166:cytology / Q000187:drug effects*; D014471:Umbilical Veins / Q000187:drug effects / Q000378:metabolism
D018501:Antirheumatic Agents; D007375:Interleukin-1; D015850:Interleukin-6; C102509:KE 758; D010654:Phenylbutyrates; D010666:Phenylpropionates; C078547:esonarimod