PF-06651600

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

PF-06651600 是一种新型有效的选择性 JAK3 抑制剂，IC50 为 0.346 nM，选择性比 JAK1 和 JAK2 高 1,000 倍；抑制 Th1 和 Th17 细胞分化和功能，减少大鼠佐剂诱导的关节炎以及小鼠实验性自身免疫性脑脊髓炎模型的疾病病理；选择性靶向 γc 细胞因子途径，同时保留 JAK1 依赖性抗炎信号传导，例如巨噬细胞中 LPS 处理后的 IL-10 抑制功能以及 IL-27 引发的巨噬细胞中 TNFα 和 IL-1β 产生的抑制。

PF-06651600 is a novel potent, selective JAK3 inhibitor with IC50 of 0.346 nM, displays >1,000-fold selectivity over JAK1 and JAK2; inhibits Th1 and Th17 cell differentiation and function, reduces disease pathology in rat adjuvant-induced arthritis as well as in mouse experimental autoimmune encephalomyelitis models; selectively targets γc cytokine pathways while preserving JAK1-dependent anti-inflammatory signaling such as the IL-10 suppressive functions following LPS treatment in macrophages and the suppression of TNFα and IL-1β production in IL-27-primed macrophages.Rheumatoid Arthritis Phase 2 Clinical(In Vitro):Ritlecitinib is a potent JAK3-selective inhibitor which can inhibit the JAK3 kinase activity with an IC50 of 33.1 nM but without activity (IC50>10?000 nM) against JAK1, JAK2, and TYK2. Ritlecitinib inhibits the phosphorylation of STAT5 elicited by IL-2, IL-4, IL-7, and IL-15 with IC50 values of 244, 340, 407, and 266 nM, respectively. Ritlecitinib also inhibits the phosphorylation of STAT3 elicited by IL-21 with an IC50 of 355 nM. Functional assessment in T-cell differentiation assays demonstrate that Ritlecitinib suppresses Th1 and Th17 differentiation as measured by IFNγ, after 5 days under Th1 conditions, and IL-17 production, after 6 days under Th17 conditions, with IC50 values of 30 nM and 167 nM, respectively. Ritlecitinib also suppresses Th1 and Th17 function as measured by the inhibition of IFNγ production (IC50=48 nM) and IL-17 production (IC50=269 nM) in cells that have been previously differentiated and rested before being treated with PF-06651600. (In Vivo):In the rat adjuvant-induced arthritis (AIA) model, Ritlecitinib reduces paw swelling with an unbound EC50 of 169 nM. Similarly, Ritlecitinib significantly reduces disease severity in the experimental autoimmune encephalomyelitis (EAE) mouse model when dosed either therapeutically at 30 or 100 mg/kg or prophylactically at 20 and 60 mg/kg. The efficacy of Ritlecitinib in these two rodent models of inflammatory and autoimmune diseases illustrates that JAK3-selective inhibition can be sufficient to have disease modifying effects in human diseases.

Ritlecitinib is a potent JAK3-selective inhibitor which can inhibit the JAK3 kinase activity with an IC50 of 33.1 nM but without activity (IC50>10?000 nM) against JAK1, JAK2, and TYK2. Ritlecitinib inhibits the phosphorylation of STAT5 elicited by IL-2, IL-4, IL-7, and IL-15 with IC50 values of 244, 340, 407, and 266 nM, respectively. Ritlecitinib also inhibits the phosphorylation of STAT3 elicited by IL-21 with an IC50 of 355 nM.Functional assessment in T-cell differentiation assays demonstrate that Ritlecitinib suppresses Th1 and Th17 differentiation as measured by IFNγ, after 5 days under Th1 conditions, and IL-17 production, after 6 days under Th17 conditions, with IC50 values of 30 nM and 167 nM, respectively. Ritlecitinib also suppresses Th1 and Th17 function as measured by the inhibition of IFNγ production (IC50=48 nM) and IL-17 production (IC50=269 nM) in cells that have been previously differentiated and rested before being treated with PF-06651600.

In the rat adjuvant-induced arthritis (AIA) model, Ritlecitinib reduces paw swelling with an unbound EC50 of 169 nM. Similarly, Ritlecitinib significantly reduces disease severity in the experimental autoimmune encephalomyelitis (EAE) mouse model when dosed either therapeutically at 30 or 100 mg/kg or prophylactically at 20 and 60 mg/kg. The efficacy of Ritlecitinib in these two rodent models of inflammatory and autoimmune diseases illustrates that JAK3-selective inhibition can be sufficient to have disease modifying effects in human diseases.

PF06651600

Angiogenesis

JAK

JAK

Inflammation/Immunology

Rheumatoid Arthritis

1792180-81-4

285.351

C15H19N5O

>98% (HPLC)

DMSO: 130 mg/mL, 455.60 mM （ < 1 mg/ml refers to the product slightly soluble or insoluble )

CC1CCC(CN1C(=O)C=C)NC2=NC=NC3=C2C=CN3

1-[(2S,5R)-2-Methyl-5-(7H-pyrrolo[2,3-d]pyrimidin-4-ylamino)-1-piperidinyl]-2-propen-1-one

(-20℃)

With Ice Pack

≥ 2 years