CP-690550

• CAT Number: A000725
• CAS Number: 477600-75-2
• Molecular Formula: C16H20N6O
• Molecular Weight: 312.37
• Purity: ≥95%
• Target: JAK
• Solubility: Soluble in DMSO
• Storage: 3 years -20C powder
• IUPAC Name: 3-[(3R,4R)-4-methyl-3-[methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]piperidin-1-yl]-3-oxopropanenitrile
• InChI: InChI=1S/C16H20N6O/c1-11-5-8-22(14(23)3-6-17)9-13(11)21(2)16-12-4-7-18-15(12)19-10-20-16/h4,7,10-11,13H,3,5,8-9H2,1-2H3,(H,18,19,20)
• InChIKey: UJLAWZDWDVHWOW-UHFFFAOYSA-N
• SMILES: CC1CCN(CC1N(C)C2=NC=NC3=C2C=CN3)C(=O)CC#N

Tofacitinib(CAS 477600-75-2) , also known as tasocitinib, CP-690550, is a Janus kinase (JAK) inhibitor.

Tofacitinib modulates the signaling pathway at the point of JAKs, preventing the phosphorylation and activation of STATs. JAK enzymes transmit cytokine signaling through pairing of JAKs (e.g., JAK1/JAK3, JAK1/JAK2, JAK1/TyK2, JAK2/JAK2). Tofacitinib inhibited the in vitro activities of JAK1/JAK2, JAK1/JAK3, and JAK2/JAK2 combinations with IC50 of 406, 56, and 1377 nM, respectively. Tofacitinib citrate was approved for for the treatment of adult patients with moderately to severely active rheumatoid arthritis who have had an inadequate response or intolerance to methotrexate. It may be used as monotherapy or in combination with methotrexate or other nonbiologic disease-modifying antirheumatic drugs (DMARDs).

Overview of Clinical Research

Tofacitinib is a Janus kinase 1/2/3 inhibitor. In 2020, Pfizer completes a phase I pharmacokinetic and safety study in healthy volunteers in USA (PO) (NCT04338711).

Reference

1: Iwamoto N, Tsuji S, Takatani A, Shimizu T, Fukui S, Umeda M, Nishino A, Horai Y, Koga T, Kawashiri SY, Aramaki T, Ichinose K, Hirai Y, Tamai M, Nakamura H, Terada K, Origuchi T, Eguchi K, Ueki Y, Kawakami A. Efficacy and safety at 24 weeks of daily clinical use of tofacitinib in patients with rheumatoid arthritis. PLoS One. 2017 May 4;12(5):e0177057. doi: 10.1371/journal.pone.0177057. eCollection 2017. PubMed PMID: 28472115.
2: Friedman S. Tofacitinib for Ulcerative Colitis – A Promising Step Forward. N Engl J Med. 2017 May 4;376(18):1792-1793. doi: 10.1056/NEJMe1701505. PubMed PMID: 28467881.
3: Sandborn WJ, Su C, Sands BE, D/'Haens GR, Vermeire S, Schreiber S, Danese S, Feagan BG, Reinisch W, Niezychowski W, Friedman G, Lawendy N, Yu D, Woodworth D, Mukherjee A, Zhang H, Healey P, Panés J; OCTAVE Induction 1, OCTAVE Induction 2, and OCTAVE Sustain Investigators.. Tofacitinib as Induction and Maintenance Therapy for Ulcerative Colitis. N Engl J Med. 2017 May 4;376(18):1723-1736. doi: 10.1056/NEJMoa1606910. PubMed PMID: 28467869.
4: Merola JF, Elewski B, Tatulych S, Lan S, Tallman A, Kaur M. Efficacy of tofacitinib for the treatment of nail psoriasis: Two 52-week, randomized, controlled phase 3 studies in patients with moderate-to-severe plaque psoriasis. J Am Acad Dermatol. 2017 Apr 7. pii: S0190-9622(17)30147-0. doi: 10.1016/j.jaad.2017.01.053. [Epub ahead of print] PubMed PMID: 28396102.
5: Maneiro JR, Souto A, Gomez-Reino JJ. Risks of malignancies related to tofacitinib and biological drugs in rheumatoid arthritis: Systematic review, meta-analysis, and network meta-analysis. Semin Arthritis Rheum. 2017 Feb 16. pii: S0049-0172(16)30306-7. doi: 10.1016/j.semarthrit.2017.02.007. [Epub ahead of print] PubMed PMID: 28284845.
6: Singh JA, Hossain A, Tanjong Ghogomu E, Mudano AS, Maxwell LJ, Buchbinder R, Lopez-Olivo MA, Suarez-Almazor ME, Tugwell P, Wells GA. Biologics or tofacitinib for people with rheumatoid arthritis unsuccessfully treated with biologics: a systematic review and network meta-analysis. Cochrane Database Syst Rev. 2017 Mar 10;3:CD012591. doi: 10.1002/14651858.CD012591. Review. PubMed PMID: 28282491.