CRK12-IN-1 is a potent CRK12 inhibitor with insecticidal activity and exhibits inhibitory effects on Trypanosoma brucei (T.b. brucei) and Trypanosoma congolense (T. congolense) with EC50s of 1.3 and 18 nM, respectively, rapidly killing the pathogenic cells.

T. congolense:1.3 nM, T. vivax:18 nM

CRK12-IN-1(compound 1) (10 mg/mL; 69 h) demonstrates exceptional potency against T.b. brucei, proving highly effective in animal models of T.b. brucei infection. Additionally, it serves as a potent inhibitor of T. congolensei, with EC50 values of 1.3 and 18 nM, respectively.[1]

CRK12-IN-1 (compound 1) demonstrates moderate blood clearance and a short half-life (~1.8 h) in male ruminating Holstein-Friesian cattle, penetrating tissues beyond the vasculature (5 mg free base/kg, i.m. or 2.5 mg free base/kg, i.v.; 0.25-120 h). It reduces parasitemia in T. congolense-infected calves but does not prevent re-emergence after treatment ends (5 mg/kg, s.c., twice 12 h apart for 4 days). In female NMRI mice, CRK12-IN-1 shows 74% bioavailability and a half-life of ~1 h (10 mg free base/kg, s.c., 0.08-8 h). It achieves sterile cure against T. congolense in mice (50 or 10 mg/kg, s.c., once daily for 4 days) and is slightly more efficacious against T. vivax-infected mice (30 or 3 mg/kg, s.c., daily for 4 days).