| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
|
||
| 25mg |
|
||
| 50mg |
|
||
| 100mg |
|
||
| 250mg |
|
||
| 500mg |
|
||
| 1g |
|
||
| Other Sizes |
|
Purity: ≥98%
Tofacitinib citrate (formerly CP-690550 citrate), the citrate salt of tofacitinib (tasocitinib or CP 690550, brand Xeljanz), is a novel, potent and orally bioavailable inhibitor of JAK3 (Janus-Associated kinase) with IC50 of 1 nM in cell-free assays. In May 2018, the U.S. FDA approved tofacitinib citrate for the treatment of adult patients with moderately to severely active ulcerative colitis. It is the first oral drug approved for chronic use in ulcerative colitis. The inhibition is JAK3 specific with a selectivity 1000-fold more than other non-JAK family kinases. Besides inhibiting JAK3 (with IC50 of 1 nM), tofacitinib also inhibits JAK2 and JAK1 with 20- and 100-fold less in potency respectively. However, in a recent study, the binding affinities (Ki) of tofacitinib towards JAK1, JAK2, and JAK3 were reported to be 1.6 nM, 21.7 nM, and 6.5 nM respectively.
| ln Vitro |
At 2.2 nM and 5 nM (Kd), tofacitinib (CP-690550) citrate binds possibly at JAK3 and JAK2. Additional binding for tofacitinib is reported for the following sites: 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]. To measure tyrosine kinase inhibitor (TKI) activity, K562, KCL22, and THP-1 cells are treated to varying dosages of STI571 or JAK inhibitors for a duration of 72 hours. The MTT assay is then used to assess the suppression of cell growth. IMA inhibits K562 and KCL22 cell proliferation in a concentration-dependent manner, but not THP-1 cell proliferation. IMA's IC50 values for K562 and KCL22 are 0.28 μM and 0.17 μM, respectively. Tofacitinib (TOF) and INCB018424 together increase the sensitivity of K562 and KCL22 to IMA, even if they do not decrease cell growth on their own[4].
|
|---|---|
| ln Vivo |
When compared to PEG-treated control mice, animals treated with tofacitinib exhibit a markedly reduced generation of anti-drug antibodies (ADAs) (during five weeks following initial immunization, p<0.01, n=8). Furthermore, day 28 is when ADAs are first noticeable. From days 21 through 35, there is a noticeable difference in titers to SS1P of 1000 to 200 times, respectively. Mice injected with keyhole limpet hemocyanin (KLH) produce antibodies more quickly than those given SS1P. However, when compared to controls, the treatment of tofacitinib lowers anti-KLH titers (p<0.05 on day 21 and p<0.01 on day 28, respectively, n = 5). Between days 21 and 28, there were reductions in titers ranging from 5000 to 250 fold, respectively[2]. A daily dose of tofacitinib of 6.2 mg/kg is chosen based on prior dose-response studies in order to produce 80% inhibition of hind paw volume and plasma exposure, which can suppress the JAK1 and JAK3 signaling pathways for more than 4 hours[3].
|
| Animal Protocol |
Mauritius-origin adult cynomolgus monkeys;
|
| References |
[1]. Jiang JK, et al. Examining the chirality, conformation and selective kinase inhibition of 3-((3R,4R)-4-methyl-3-(methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino)piperidin-1-yl)-3-oxopropanenitrile (CP-690,550). J Med Chem. 2008 Dec 25;51(24):8012-8.
[2]. Onda M, et al. Tofacitinib suppresses antibody responses to protein therapeutics in murine hosts. J Immunol. 2014 Jul 1;193(1):48-55. [3]. LaBranche TP, et al. JAK inhibition with tofacitinib suppresses arthritic joint structural damage through decreased RANKL production. Arthritis Rheum. 2012 Nov;64(11):3531-42. [4]. Yagi K, et al. Pharmacological inhibition of JAK3 enhances the antitumor activity of STI571 in human chronic myeloid leukemia. Eur J Pharmacol. 2018 Apr 15;825:28-33 |
| Molecular Formula |
C22H28N6O8
|
|---|---|
| Molecular Weight |
504.4931
|
| CAS # |
540737-29-9
|
| Related CAS # |
Tofacitinib;477600-75-2;Tofacitinib-d3 citrate;2701680-77-3;(3S,4S)-Tofacitinib;1092578-47-6;(3R,4S)-Tofacitinib;1092578-46-5;(3S,4R)-Tofacitinib;1092578-48-7
|
| SMILES |
O=C(C([H])([H])C#N)N1C([H])([H])C([H])([H])[C@@]([H])(C([H])([H])[H])[C@]([H])(C1([H])[H])N(C([H])([H])[H])C1C2C([H])=C([H])N([H])C=2N=C([H])N=1.O([H])C(C(=O)O[H])(C([H])([H])C(=O)O[H])C([H])([H])C(=O)O[H]
|
| Synonyms |
CP-690550; CP690550; CP 690550; Tasocitinib; Tofacitinib; Xeljanz (Trade name); CP-690550-10; CP-690,550-10; CP-690550 citrate;
|
| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
|
| Solubility (In Vitro) |
DMSO: 100 mg/mL (198.2 mM)
Water:<1 mg/mL
Ethanol:<1 mg/mL
|
|---|---|
| Solubility (In Vivo) |
0.5% methylcellulose:30mg/mL (Please use freshly prepared in vivo formulations for optimal results.)
|
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.9822 mL | 9.9110 mL | 19.8220 mL | |
| 5 mM | 0.3964 mL | 1.9822 mL | 3.9644 mL | |
| 10 mM | 0.1982 mL | 0.9911 mL | 1.9822 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
| NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT06202560 | Enrolling by invitation | Drug: Tofacitinib 5 MG | Frontal Fibrosing Alopecia Lichen Planopilaris |
Institute of Dermatology, Thailand | November 29, 2023 | Not Applicable |
| NCT06044844 | Recruiting | Drug: Tofacitinib | Efficacy of Tofacitinib in the Systemic Sclerosis |
Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh |
November 2023 | Phase 2 |
| NCT04424303 | Recruiting | Drug: Tofacitinib | Ulcerative Colitis | Pfizer | December 4, 2020 | |
| NCT06278402 | Completed | Drug: Tofacitinib | Alopecia Areata Alopecia Totalis |
Jinnah Hospital | July 1, 2023 | Phase 3 |
|
CP-690,550 inhibits signal transducer and activator of transcription (STAT)3 nuclear localization in both murine cell lines.Cancer Sci.2008 Jun;99(6):1265-73. |
Effect of CP-690,550 on ex vivo expanded erythroid progenitors.Cancer Sci.2008 Jun;99(6):1265-73. |
CP-690,550-induced poly (ADP-ribose) polymerase (PARP) and caspase-3 cleavage.Cancer Sci.2008 Jun;99(6):1265-73. |
CP-690,550 modulates immunolocalization of signal transducer and activator of transcription (STAT)3.Cancer Sci.2008 Jun;99(6):1265-73. |
 |
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
COA
