MBP146-78

MBP146-78 is a potent and selective inhibitor of cGMP dependent protein kinases.

MBP146-78 displays a dose-dependent inhibition of T. gondii tachyzoites replicating inside HFFs, with an IC50 of 210 nM. The suppression of lytic parasite growth by MBP146-78 is reversible. Replacement of the medium with medium lacking MBP146-78, after treatment for up to 7 days at 2 uM, results in complete lysis of HFF cell monolayers. MBP146-78 is neither toxic nor inhibitory to proliferating or confluent monolayers of HFFs at concentrations of up to 10 uM[1].

In infected mice that are treated with MBP146-78 at 50 mg/kg twice daily, parasites are undetectable throughout the 10-day treatment period in each of the tissues examined. However, samples from brain, spleen, and lung taken from infected treated mice reveal the presence of parasites after cessation of administration of MBP146-78, indicating that a transient asymptomatic parasite recrudescence occurs in all survivors. The ability of mice to control Toxoplasma infection after MBP146-78 treatment has been terminated suggests that the mouse immune system plays a synergistic role with chemotherapy in controlling the infection[1].

References:
[1]. Nare B, et al. Evaluation of a cyclic GMP-dependent protein kinase inhibitor in treatment of murine toxoplasmosis: gamma interferon is required for efficacy. Antimicrob Agents Chemother. 2002 Feb;46(2):300-7.