JAK-IN-20

JAK-IN-20 is a potent, pan and orally active JAK inhibitor with an IC50s of 7 nM, 5 nM, 14 nM for JAK1, JAK2, JAK3, respectively. JAK-IN-20 shows excellent pharmacokinetics and displays anti-inflammatory efficacy in vivo[1].

Signaling Pathways >> JAK/STAT Signaling >> JAK

Signaling Pathways >> Epigenetics >> JAK

Signaling Pathways >> Stem Cell/Wnt >> JAK

Research Areas >> Inflammation/Immunology

JAK1:7 nM (IC50)

JAK2:5 nM (IC50)

JAK3:14 nM (IC50)

JAK-IN-20 (compound 32) (3 mg/kg for p.o.; 1 mg/kg for i.v.) shows excellent pharmacokinetics in rats[1]. JAK-IN-20 (10 mg/kg; p.o.; once a day for 3 days) shows anti-inflammatory effect[1]. Pharmacokinetic Parameters of JAK-IN-20 in female Sprague Dawley rats[1]. parameter 32 PO Dose (mg/kg) 3 Tmax (h) 0.63(0.25-6) Cmax (µg/mL) 7.82±3.68 AUC0-t (µg.h/mL) 80.18±35.44 T1/2,po (h) 4.77±1.84 MRT (h) 7.54±2.52 IV Dose (mg/kg) 1 C0 (µg/mL) 4.70±2.50 AUC0-t (µg.h/mL) 18.89±1.76 Vss (L/kg) 0.32±0.14 CL (mL/min/kg) 0.85±0.13 T1/2,iv (h) 5.16±3.83 MRT (h) 6.69±4.03 %F 100Wistar rats; 3 mg/kg; p.o. (1% Tween 80 + 99% (0.5%) methyl cellulose in water); 1 mg/kg; i.v. (5% NMP + 5% solutol + 90% normal saline)[1] Animal Model: 7-10 weeks, 250-300g, male wistar rats[1] Dosage: Administration: 3 mg/kg for p.o.; 1 mg/kg for i.v. Result: Showed fast oral absorption, higher plasma exposure, extended oral half-life and excellent oral bioavailability of 100%. Animal Model: Female Sprague Dawley rats ( PGPS rat model)[1] Dosage: 10 mg/kg Administration: P.o.; once a day; 3 days Result: Showed anti-inflammatory effect.

[1]. Desai J, et al. Optimisation of momelotinib with improved potency and efficacy as pan-JAK inhibitor. Bioorg Med Chem Lett. 2022; 66:128728.