RAI-20 (H018) is an orally active JAK1/JAK2 dual inhibitor ( IC50 =15.1 and 22.7 nM). RAI-20 exhibits excellent pharmacokinetic properties, including plasma stability, systemic exposure, and a long half-life. In a collagen-induced arthritis rat model, RAI-20 shows significant anti-inflammatory and anti-arthritic activities, effectively reducing paw swelling volume and arthritis index. RAI-20 can be used for research on the pathogenesis of rheumatoid arthritis [1].
In Vivo, RAI-20 (2-10 mg/kg; p.o.; daily; 14 days) elicits potent, dose-dependent anti-arthritic activity in Lewis rats with collagen-induced arthritis, with the 10 mg/kg daily oral dose producing the greatest reductions in hind paw volume and arthritis index[1].
In Vitro, RAI-20 (3×10- serial dilutions; under standard cell culture conditions) potently inhibits Ba/F3 cell proliferation with an IC50 of 1.21 μM[1]. RAI-20 (serial dilutions; 10 min compound pre-incubation, 10 min IL-6 stimulation) inhibits IL-6-induced pSTAT1 expression in human whole blood cells with an IC50 of 1.45 μM[1]. RAI-20 (up to 10 μM (CYP inhibition), serial dilutions (other assays); incubated to measure T1/2 (plasma stability, hepatic microsomal stability)) exhibits favorable in vitro pharmacokinetic properties including prolonged human plasma stability, moderate hepatic microsomal metabolism, high plasma protein binding, no significant CYP inhibition, and hERG inhibition with an IC50 of 11.5 μM[1].
References:
[1]. Zhu H, et al. Discovery of selective JAK1/2 inhibitor H018, a phase II agent with demonstrated preclinical anti-rheumatoid arthritis activity. Eur J Med Chem. Published online March 2, 2026.
In Vivo, RAI-20 (2-10 mg/kg; p.o.; daily; 14 days) elicits potent, dose-dependent anti-arthritic activity in Lewis rats with collagen-induced arthritis, with the 10 mg/kg daily oral dose producing the greatest reductions in hind paw volume and arthritis index[1].
In Vitro, RAI-20 (3×10- serial dilutions; under standard cell culture conditions) potently inhibits Ba/F3 cell proliferation with an IC50 of 1.21 μM[1]. RAI-20 (serial dilutions; 10 min compound pre-incubation, 10 min IL-6 stimulation) inhibits IL-6-induced pSTAT1 expression in human whole blood cells with an IC50 of 1.45 μM[1]. RAI-20 (up to 10 μM (CYP inhibition), serial dilutions (other assays); incubated to measure T1/2 (plasma stability, hepatic microsomal stability)) exhibits favorable in vitro pharmacokinetic properties including prolonged human plasma stability, moderate hepatic microsomal metabolism, high plasma protein binding, no significant CYP inhibition, and hERG inhibition with an IC50 of 11.5 μM[1].
References:
[1]. Zhu H, et al. Discovery of selective JAK1/2 inhibitor H018, a phase II agent with demonstrated preclinical anti-rheumatoid arthritis activity. Eur J Med Chem. Published online March 2, 2026.