Target: NAD+-dependent type-I 15-hydroxy PGDH
IC50: 26.4 nM
Ki: 5 nM
STK393606 is a competitive inhibitor of NAD+-dependent type-I 15-hydroxy PGDH, with the IC50 value of 26.4±2.4 nM, and the Ki value of 5 nM, which could cause a maximum of 100% inhibition [1].
Hydroxyprostaglandin dehydrogenase 15-(NAD), also called 15-hydroxy prostaglandin dehydrogenase (15-hydroxy PGDH), is a critical enzyme participated in the inactivation of prostaglandins (PGs) and related eiscosanoids. 15-hydroxy PGDH belongs to the family of oxidoreductases, specifically those acting on the CH-OH group of substrates with NAD+ or NADP+ as acceptor. 15-hydroxy PGDH could catalyze the oxidation of primary PGs to their 15-keto metabolites [2]. Radioimmunoassay for 15-hydroxy prostaglandin dehydrogenase had identified two types of enzyme activity, of which type-I used NAD+ as a cofactor, while type-II used NADP+ as a cofactor and bear wider substrate specificity [3].
In Vitro: no data available.
In Vivo: no data available.
Clinical trial: no data available.
References:
[1] Niesen F H, Schultz L, Jadhav A, et al. High-Affinity Inhibitors of Human NAD + -Dependent 15-Hydroxyprostaglandin Dehydrogenase: Mechanisms of Inhibition and Structure-Activity Relationships[J]. PLOS ONE, 2010, 5(11).
[2] Tai H, Ensor C M, Tong M, et al. Prostaglandin catabolizing enzymes.[J]. Prostaglandins & Other Lipid Mediators, 2002: 483-493.
[3] Lee S C, Levine L. Prostaglandin metabolism. II. Identification of two 15-hydroxyprostaglandin dehydrogenase types.[J]. Journal of Biological Chemistry, 1975, 250(2): 548-552.