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化学名
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4-(((1R,2r,3S,5s,7s)-5-hydroxyadamantan-2-yl)amino)-7H-pyrrolo[2,3-b]pyridine-5-carbimidic acid
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分子式
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C18H22N4O2
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详细内容
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Peficitinib (ASP015K) is an oral Janus kinase (JAK) inhibitor. It inhibits enzyme activities of JAK1, JAK2, JAK3 and Tyk2 with IC50 values of 3.9, 5.0, 0.71 and 4.8 nmol/L, respectively. It showed moderate selectivity for JAK3 inhibition [1].
JAK family of non-receptor protein tyrosine kinases includes JAK1, JAK2, JAK3 and tyrosine kinase 2 (Tyk2). JAK1, JAK2, JAK3 and Tyk2 are critically important in haematopoietic cells and immune cells [1].
Erythropoietin regulates haematopoiesis (the production of blood cells) [2]. 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) [3].
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 [4].
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