CRK12-IN-1

CRK12-IN-1 is a potent CRK12 inhibitor. CRK12-IN-1 is extremely potent against T.b. brucei and rapidly cytocidal, as well as equally potent against T. congolense and T. vivax (EC50 of 1.3 and 18 nM, respectively)[1].

Research Areas >> Infection

EC50: 1.3 nM (T. congolense), 18 nM (T. vivax)[1]

CRK12-IN-1 (compound 1) (10 mg/mL; 69 hours) is extremely potent against T.b. brucei and in animal models of T.b. brucei infection, as well as a potent inhibitor of T. congolensei (EC50 of 1.3 and 18 nM, respectively)[1].

CRK12-IN-1 (compound 1) (50 or 10 mg/kg; s.c.; once daily for 4 days) can elicit sterile cure in against T. congolense infected mice, also has the same effect but marginally more efficacious (30 or 3 mg/kg; s.c.; daily, for 4 days) in against T. vivax infected mice[1]. CRK12-IN-1 (5 mg/kg, s.c., twice 12 h apart for 4 days) can suppress parasitaemia below the level of detection in T. congolense infected calves, but parasitaemia quickly re-emerges following the cessation of treatment[1]. CRK12-IN-1 (10 mg free base/kg; s.c.; for 0.08-8 hours) has 74% of bioavailability with a half-life of about 1 hour in female NMRI mice[1]. CRK12-IN-1 (i.m. at 5 mg free base/kg or i.v. at 2.5 mg free base/kg; 0.25-120 hours) has a moderate clearance from the blood and a relatively short half-life (about1.8 h) in male ruminating Holstein-Friesian, and penetrate tissues beyond the vasculature[1].

[1]. Smith A, et al. Repositioning of a Diaminothiazole Series Confirmed to Target the Cyclin-Dependent Kinase CRK12 for Use in the Treatment of African Animal Trypanosomiasis [published online ahead of print, 2022 Mar 18]. J Med Chem. 2022;10.1021/acs.jmedchem.1c02104.