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Tofacitinib

CAS No. : 477600-75-2

產(chǎn)品活性：Tofacitinib is an orally available JAK3/2/1 inhibitor with IC₅₀s of 1, 20, and 112 nM, respectively.

研究領(lǐng)域：Epigenetics  |  Protein Tyrosine Kinase/RTK  |  JAK/STAT Signaling  |  Stem Cell/Wnt  |  Apoptosis

作用靶點：JAK  |  Apoptosis

In Vitro: Tofacitinib (CP-690550) citrate binds potentially at JAK3 and JAK2 as 2.2 nM and 5 nM (K_d). The report includes additional binding for Tofacitinib at Camk1 (K_d of 5,000 nM), DCamkL3 (K_d of 4.5 nM), Mst2 (K_d of 4,300 nM), Pkn1 (K_d of 200 nM), Rps6ka2 (Kin.Dom.2-C-terminal) (K_d of 1,400 nM), Rps6ka6 (Kin.Dom.2-C-terminal) (K_d of 1,200 nM), Snark (K_d of 420 nM), Tnk1 (K_d of 640 nM) and Tyk2 (K_d of 620 nM).

In Vivo: Animals that are treated with Tofacitinib show a significantly lower production of anti-drug antibodies (ADAs) compare with PEG-treated control mice (for five weeks after initial immunization, p<0.01, n=8). Moreover ADAs become detectable earliest on day 28. A difference of 1000- to 200-fold in titers to SS1P is apparent from days 21 through 35, respectively. Compare to SS1P, mice injected with keyhole limpet hemocyanin (KLH) generate a more rapid antibody response. Yet, the administration of Tofacitinib reduces anti-KLH titers compare to controls (p<0.05 on day 21, p<0.01 on day 28, respectively, n=5). Reductions in titers ranged from 5000- to 250-fold from days 21 through 28, respectively. Based on previous dose-response studies, a daily dose of Tofacitinib of 6.2 mg/kg is selected to provide 80% inhibition of hind paw volume and plasma exposure capable of suppressing the JAK1 and JAK3 signaling pathways for >4 hours.

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