Ro 28-1675

Ro 28-1675 (Ro 0281675) is a potent allosteric GK activator with a SC1.5 value of 0.24± 0.0019 uM. IC50 value: 0.24± 0.0019 uM (SC1.5) [1]Target: Glucokinase activatorThe R stereoisomer Ro 28-1675 activated GK with a SC1.5 of 0.24 uM, while the S isomer did not activated GK up to 10 uM. Oral administration of Ro 28-1675 (50 mg/Kg) to male C57B1/6J mice caused a statistically significant reduction in fasting glucose levels and improvement in glucose tolerance relative to the vehicle treated animals [1]. Comparison of rat PK parameters indicated that Ro 28-1675 displayed lower clearance and higher oral bioavailability compared to 9a. Following a single oral dose, Ro 28-1675 reduced fasting and postprandial glucose levels following an OGTT, was well tolerated, and displayed no adverse effects related to drug administration other than hypoglycemia at the maximum dose (400 mg). [1]

[1]. Fenner D, et al. Generation of N-ethyl-N-nitrosourea (ENU) diabetes models in mice demonstrates genotype-specific action ofglucokinase activators. J Biol Chem. 2011 Nov 11;286(45):39560-39572. [2]. Haynes NE, et al. Discovery, structure-activity relationships, pharmacokinetics, and efficacy of glucokinase activator (2R)-3-cyclopentyl-2-(4-methanesulfonylphenyl)-N-thiazol-2-yl-propionamide (RO0281675).