JAK-IN-21

JAK-IN-21 (Example 4) is a selective and potent JAK inhibitor with IC50s of 1.73, 2.04, 109 and 62.9 nM against JAK1, JAK2, J2V617F and TYK2, respectively[1].

Research Areas >> Cancer

Signaling Pathways >> JAK/STAT Signaling >> JAK

Signaling Pathways >> Epigenetics >> JAK

Signaling Pathways >> Stem Cell/Wnt >> JAK

JAK1:1.73 nM (IC50)

JAK2:2.04 nM (IC50)

Tyk2:62.9 nM (IC50)

JAK2-V617F:109 nM (IC50)

JAK-IN-21 (Example 4) doses not inhibit CYPs and shows good liver microsome stability[1].

JAK-IN-21 (Example 4) shows low bioavailability (F=1.9%)[1]. Animal Model: SD rats[1] Dosage: 10 mg/kg Administration: Oral gavage (Pharmacokinetic Study) Result: Rat Colon Pharmacokinetic Study[1] Compound Plasma Cmax (ng/mL) Plasma AUC (h*ng/mL) t1/2 (h) Colon AUC (h*ng/g) Colon + Feces AUC (h*ng/g) JAK-IN-21 68.8 96 1.6 6,623 545,501 Animal Model: SD rats[1] Dosage: 1 mg/kg or 2 mg/kg Administration: Intravenous injection (1 mg/kg) or oral gavage (2 mg/kg) (Pharmacokinetic Study) Result: Pharmacokinetic Parameters in Sprague-Dawley Rats by Intravenous Administration and Oral Administration[1] Compound Dose (mg/kg) AUC (h*ng/mL) T1/2 (h) Cl (mL/min/kg) Vd (L/kg) Cmax (ng/mL) F (%) JAK-IN-21 (iv) 1 854.8 0.22 19.4 0.37 JAK-IN-21 (ig) 2 29.8 0.38 40.4 1.9

[1]. Zhaokui WAN, et al. Benzamides of pyrazolyl-amino-pyrimidinyl derivatives, and compositions and methods thereof. Patent WO2020119819.