|
化学名
|
2-hydroxypropane-1,2,3-tricarboxylic acid;3-[(3R,4R)-4-methyl-3-[methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]piperidin-1-yl]-3-oxopropanenitrile
|
分子式
|
C16H20N6O.C6H8O7
|
|
详细内容
|
Tofacitinib citrate is an orally available JAK1/2/3 inhibitor with IC50s of 1, 20, and 112 nM, respectively.
Tofacitinib (CP-690550) citrate binds potentially at JAK3 and JAK2 as 2.2 nM and 5 nM (Kd). The report includes additional binding for Tofacitinib at Camk1 (Kd of 5,000 nM), DCamkL3 (Kd of 4.5 nM), Mst2 (Kd of 4,300 nM), Pkn1 (Kd of 200 nM), Rps6ka2 (Kin.Dom.2-C-terminal) (Kd of 1,400 nM), Rps6ka6 (Kin.Dom.2-C-terminal) (Kd of 1,200 nM), Snark (Kd of 420 nM), Tnk1 (Kd of 640 nM) and Tyk2 (Kd of 620 nM)[1]. K562, KCL22, and THP-1 cells are exposed to different doses of STI571 or JAK inhibitors for 72 h to quantify the effects of tyrosine kinase inhibitor (TKI) activity. Cell growth inhibition is then evaluated using the MTT assay. The proliferation of K562 and KCL22 cells, but not THP-1 cells, is inhibited by IMA in a concentration-dependent manner. The IC50 value of IMA is 0.28 μM for K562 and 0.17 μM for KCL22. Although treatment with Tofacitinib (TOF) or INCB018424 alone does not suppress cell proliferation, both Tofacitinib and INCB018424 make the K562 and KCL22 more sensitive to IMA[4].
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, p4 hours[3].
|