Tofacitinib

SKU: orb1224990

Description

Tofacitinib (CP-690550) is 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).\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: 477600-75-2
• MW: 312.37
• Purity: >98% (HPLC)
• Formula: C₁₆H₂₀N₆O
• SMILES: C[C@@H]1CCN(C[C@@H]1N(C)C2=NC=NC3=C2C=CN3)C(=O)CC#N
• Target: JAK
• Solubility: DMSO

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).

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

CP-690550

Quick Database Links

Gene Symbol

JAK