J. Tanaka
Nov 1, 2001
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Journal
Nihon rinsho. Japanese journal of clinical medicine
Abstract
Orally available anti-diabetic candidates, reported by Merck researchers, are reviewed. The lead, asterriquinone B1(1a), was discovered in a fungal extract by screening with the cell line CHO.IR. An analog, 2,5-dihydroxy-3-(1-methylindol-3-yl)-6-phenyl-1,4-benzoquinone(2h), was selected by studying structure-activity relationships with various in vitro and in vivo tests. Analog 2h exhibited selective tyrosin kinase activity to an insulin receptor and a glucose-lowering effect by testing on diabetic rodent models. However, on the basis of the results of in vivo tests on streptozotocin-induced and on normal lean mice, the activity of 2h was attributed to a sensitizing effect on insulin together with an insulin mimetic effect in part. These studies shed light on the search for new anti-diabetic agents by targeting insulin receptors.