JAK3-IN-6 is irreversible Janus Associated Kinase 3 (JAK3) inhibitor, with an IC50 of 0.15 nM

JAK3:0.15 nM

一种强效的JAK3抑制剂（0.15 nM）在酶类实验中对JAK3的选择性是对JAK1的4300倍，而在细胞报告实验中对IL-2相比IL-6的选择性是67倍，对IL-2相比EPO或GMCSF的选择性是140倍，在人类PBMC实验中对IL-7相比IL-6或GMCSF的选择性是大于35倍。在体内，选择性抑制JAK3足以阻断炎症在类风湿关节炎大鼠模型中的发展，并且不影响造血。

Female Lewis rats were purchased and housed . 48 rats were divided into six groups (n=8/group). Group 1 were drug-na?ve i.e. no compounds were administered throughout the study. On the afternoon of Day 1 (4pm), ABT or vehicle (1 ml/kg p.o.) was administered to Groups 2-5. Days 2-11 (8 am), each animal in Groups 2-5 were administered ABT 10 mpk qd (1 ml/kg p.o.), immediately followed by either vehicle or compound at 5ml/kg p.o. Group 6 animals received vehicle only (5 ml/kg p.o.). Days 2-11 (4 pm) Groups 2-5 were administered vehicle or compound at 5 ml/kg p.o. Animals were monitored and weighed throughout the study. On Day 10, under isoflurane anesthesia, 3 animals from Groups 2-6 were bled via the jugular vein for PK analysis at 4 and 8 h post-8 am dose. On Day 11, blood samples were collected, as described above, at 0 (16 h post-Day 10 pm dose) and 2 h post-am dose for PK, hematology, and clinical chemistry analysis. All remaining animals were euthanized at 2 hrs post-dosing on Day 11 and blood samples were collected for PK, hematology, and clinical chemistry analysis. Data were analyzed using Graphpad prism software. Statistical analyses were performed using a one-way ANOVA with Dunnett s post-hoc test for group comparisons to ABT + vehicle treatment.