Tofacitinib citrate

SKU: orb1224747

Description

A potent, specific, orally active inhibitor of JAK3 with IC50 of 1 nM in cell-free assays; displays 20- to 100-fold less potency for JAK2 and JAK1 (IC50=20 nM and 112 nM, respectively), and shows no potent activity against 30 other kinases at >3 uM (CaMK1, ROCK2, Lck, MST2, etc.); effectively inhibits a murine mixed lymphocyte reaction (MLR) with IC50 of 91 nM, significantly prolonges survival in a murine model of heart transplantation and in cynomolgus monkeys receiving kidney transplants.Rheumatoid Arthritis Approved(In Vitro):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). 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.\n(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, p4 hours.

Key Properties

• CAS Number: 540737-29-9
• MW: 504.4931
• Purity: >98% (HPLC)
• Formula: C₂₂H₂₈N₆O₈
• SMILES: C[C@@H]1CCN(C[C@@H]1N(C)C2=NC=NC3=C2C=CN3)C(=O)CC#N.C(C(=O)O)C(CC(=O)O)(C(=O)O)O
• Target: JAK
• Solubility: DMSO: ≥ 122.5 mg/mL

Bioactivity

• In Vivo:
  Animals that are treated with Tofacitinib show a significantly lower production of anti-drug antibodies (ADAs) compared 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. compared with SS1P, mice injected with keyhole limpet hemocyanin (KLH) generate a more rapid antibody response. Yet, the administration of Tofacitinib reduces anti-KLH titers compared with 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.
• In Vitro:
  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). 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.

Storage & Handling

• Storage: Storage temperature: -20°C. Stability: ≥ 2 years
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

Tasocitinib citrate | CP-690550 citrate | CP 690550 citrate | CP690550 citrate

Quick Database Links

Gene Symbol

JAK