Thiazolidine,3-[(2S,3S)-2-aMino-3-Methyl-1-oxopentyl]-, (2E)-2-butenedioate (2:1)

Uses

P32/98 is a dipeptidyl peptidase IV inhibitor which is used in hypertensive patients treated with antihpertensive drugs.

Biological Activity

ki: 126 nmp32/98 (hemifumarate) is an inhibitor of dpp iv.glucose-dependent insulinotropic polypeptide (gip) and glucagon-like peptide 1 (glp-1) are responsible for >50% of nutrient-stimulated insulin secretion. after being released into the circulation, gip and glp-1 are quickly inactivated by the circulating enzyme dipeptidyl peptidase iv (dpp iv).

in vitro

p32/98 was found to be able to block adipogenesis dose-dependently, starting at the concentration of 100 μm, and p32/98 could completely block adipogenesis in 3t3-l1 cell line at 500 μm concentration. in addition, the inhibitory effects of p32/98 was further confirmed by detecting the expression of adipocyte markers at the end of differentiation [1].

in vivo

in previou animal study, two groups of fa/fa zucker rats were orally treated twice daily for three months with p32/98 at 20 mg/kg/day and monthly oral glucose tolerance tests (ogtts) were conducted after drug washout. results showed that after 12 weeks of p32/98 treatment, the peak ogtt blood glucose values in the treated rats averaged 8.5 mmol/l less than in the controls. in addition, the concomitant insulin resulted in an increased early-phase insulin response in the treated group. moreover, in response to an 8.8 mmol/l glucose perfusion, pancreata from controls showed no increase in insulin secretion, while pancreata from p32/98-treated animals had a 3.2-fold rise in insulin secretion [2].

References

1. han r, wang x, bachovchin w, zukowska z, osborn jw. inhibition of dipeptidyl peptidase 8/9 impairs preadipocyte differentiation. sci rep. 2015 aug 5;5:12348. 2. j. a. pospisilik, s. g. stafford, h. u. demuth, et al. long-term treatment with the dipeptidyl peptidase iv inhibitor p32/98 causes sustained improvements in glucose tolerance, insulin sensitivity, hyperinsulinemia, and β-cell glucose responsiveness in vdf (fa/fa) zucker rats. diabetes 51, 943-950 (2002).