product name Peficitinib (ASP015K)
Description: Peficitinib, also known as ASP015K and JNJ-54781532, is an orally bioavailable JAK inhibitor. It demonstrated potent efficacy in adjuvant-induced arthritis model in rats. ASP015K inhibited JAK1, JAK2, JAK3 and TYK2 enzyme activities with IC50 values of 3.9, 5.0, 0.71 and 4.8 nM, respectively. ASP015K inhibited the IL-2-induced proliferation of human T cells with an IC50value of 18 nM. Moreover, ASP015K was 14-fold more potent against JAK1/3 than JAK2/2 on the basis of EPO-induced proliferation of human leukemia cells. ASP015K has the potential to demonstrate JAK1/3-mediated immunomodulatory effects without the occurrence of JAK2-mediated hematopoietic effects.
References: Arthritis Rheumatol. 2016 Oct 16. doi: 10.1002/art.39955; Ann Rheum Dis. 2016 Jun;75(6):1057-64.
326.39
Formula
C18H22N4O2
CAS No.
944118-01-8
Storage
-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)
DMSO: 65 mg/mL (199.1 mM)
Water: <1 mg/mL
Ethanol: <1 mg/mL
Solubility (In vivo)
Synonyms
other peoduct :
| In Vitro |
In vitro activity: ASP015K suppresses the IL-2-induced proliferation of human T cells with greater potency than EPO-induced proliferation of human erythroleukemia cells. In human whole blood, ASP015K inhibits STAT5 phosphorylation (pSTAT5). Kinase Assay: Cell Assay: Erythropoietin regulates haematopoiesis (the production of blood cells). Treatment with ASP015K inhibited the human T-cell proliferation induced by IL-2. And this effect was greater than the effect to inhibit EPO-induced human erythroleukemia cell proliferation. In human whole blood, ASP015K concentration-dependently inhibited STAT5 phosphorylation (pSTAT5). |
|---|---|
| In Vivo | In the rat AIA model, ASP015K (p.o.) significantly decreases paw swelling and ankle bone destruction score. |
| Animal model | In healthy volunteers, STAT5-P was dose-dependently inhibited by ASP015K. When the doses of ASP015K were 60, 120, 200, or 300 mg, the mean peak percentage inhibitions of STAT5-P were 84%, 85%, 92%, and 93%, respectively. Plasma ASP015K inhibited STAT5-P with an EC50 value of 48 ng/mL, a shape factor (γ) of ~1.2, and an estimated Emax close to 100%. On days 1, 7, and 14, at ~2 hours after treatment with ASP015K at multiple doses, the peak of median percentage of STAT5-P inhibition appeared. |
| Formulation & Dosage | |
| References | Arthritis Rheumatol. 2016 Oct 16. doi: 10.1002/art.39955; Ann Rheum Dis. 2016 Jun;75(6):1057-64. |
