Background:

Tolimidone is a potent and selective allosteric activator of Lyn kinase with an EC50 of 63 nM.

Incubation of Tolimidone (MLR-1023) with Lyn kinase elicits a repeatable 50% increase in enzyme activity. Tolimidone elicits a concentration-dependent increase in Lyn kinase activation with a 2.3- and 2.1-fold increase achieved at concentrations of 3 and 10 μM, respectively. Inclusion of Tolimidone (100 μM) increases Lyn kinase activity by 3-fold at each ATP concentration tested (Vmax=2601 U/mg). Tolimidone-mediated activation of Lyn kinase increases in proportion to the length of preincubation period in the absence of ATP[1].

Administration of Tolimidone (MLR-1023) (30 mg/kg i.p.) significantly (p<0.05) lowers blood glucose levels to 148 and 158 mg/dL, 30 and 90 min after administration, respectively. Tolimidone significantly increases adipocyte differentiation and adiponectin production by 3.7- and 19-fold, respectively[1]. Tolimidone elicits a dose-dependent potentiation of the insulin response, with a maximal effect observed with a dose level of 30 mg/kg[2].

Reference:
[1]. Saporito MS, et al. MLR-1023 is a potent and selective allosteric activator of Lyn kinase in vitro that improves glucose tolerance in vivo. J Pharmacol Exp Ther. 2012 Jul;342(1):15-22.
[2]. Ochman AR, et al. The Lyn kinase activator MLR-1023 is a novel insulin receptor potentiator that elicits a rapid-onset and durable improvement in glucose homeostasis in animal models of type 2 diabetes. J Pharmacol Exp Ther. 2012 Jul;342(1):23-32.