Tofacitinib
- CAS No.
- 477600-75-2
- Chemical Name:
- Tofacitinib
- Synonyms
- 3-((3R,4R)-4-methyl-3-(methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino)piperidin-1-yl)-3-oxopropanenitrile;Tasocitinib;Tofacitinib base;Tofacitinib (CP-690550,Tasocitinib);Tofactinib;CS-344;CP 690550;Tofatinib;ofacitinib;Tofacitinb
- CBNumber:
- CB0970901
- Molecular Formula:
- C16H20N6O
- Molecular Weight:
- 312.38
- MOL File:
- 477600-75-2.mol
- MSDS File:
- SDS
- Modify Date:
- 2024/12/23 19:56:12
| Density | 1.3 |
|---|---|
| storage temp. | -20°C |
| solubility | Soluble in DMSO (up to 100 mg/ml) or in Ethanol (up to 100 mg/ml). |
| form | Pale powder. |
| pka | 6.04±0.60(Predicted) |
| color | Off-white |
| Stability | Stable for 1 year from date of purchase as supplied. Solutions in DMSO or ethanol may be stored at -20°C for up to 3 months. |
| InChI | InChI=1/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)/t11-,13+/s3 |
| InChIKey | UJLAWZDWDVHWOW-BCFRMRSDNA-N |
| SMILES | N([C@@H]1[C@@H](CCN(C(=O)CC#N)C1)C)(C1N=CN=C2NC=CC=12)C |&1:1,2,r| |
| CAS DataBase Reference | 477600-75-2 |
SAFETY
Risk and Safety Statements
| Symbol(GHS) |  GHS09 |
|---|---|
| Signal word | Warning |
| Hazard statements | H410 |
| Precautionary statements | P501-P273-P391 |
| HS Code | 29335990 |
| Hazardous Substances Data | 477600-75-2(Hazardous Substances Data) |
Tofacitinib Chemical Properties,Uses,Production
Description
In November 2012, the US FDA approved tofacitinib (also referred to as CP-690550) for the treatment of adult patients with moderate to severely active rheumatoid arthritis (RA) who have had an inadequate response or intolerance to methotrexate. Tofacitinib is the first small molecule kinase inhibitor approved for the treatment of RA. Tofacitinib is an inhibitor of the four subtypes of Janus kinase (JAK): JAK1, JAK2, JAK3, and Tyk2. The JAKs are intracellular, nonreceptor tyrosine kinases that play important roles in the signal transduction pathway of many cytokines (e.g., interleukins 2, 4, 7, 9, 15, and 21) and are involved in the propagation of inflammation in RA. Tofacitinib acts by inhibiting the phosphorylation and activation of signal transducers and activators of transcription (STATs), thereby suppressing the production of inflammatory mediators in joint tissue. At the enzyme level, tofacitinib inhibits JAKs 1, 2, 3, and Tyk2 with IC50s of 3.2, 4.1, 1.6, and 34 nM, respectively. At the cellular level, tofacitinib inhibits the in vitro activities of JAK1/JAK2, JAK1/JAK3, and JAK2/JAK2 combinations with IC50s of 406, 56, and 1377 nM, respectively.
Chemical Properties
Light Pink to Pale Orange Solid
Characteristics
Class: non-receptor tyrosine kinase
Treatment: RA, PA, JIA, UC
Oral bioavailability = 74%
Elimination half-life = 3.2 h
Protein binding = 40%
Uses
CP-690550 is a pyrrolo[2,3-d]pyrimidine derivative, as Janus kinase inhibitor for treatment of rheumatoid arthritis
Indications
The JAK family includes four isoforms, JAK1, JAK2, JAK3, and tyrosine kinase (TYK2). Ruxolitinib (Jakafi(R), Incyte Corp.) was the first approved JAK inhibitor, which inhibits both JAK1 and JAK2, used for the treatment of different types of myelofibrosis. Tofacitinib (Xeljanz(R), Pfizer) was approved by FDA as a JAK3-selective inhibitor for the treatment of rheumatoid arthritis and is one of the only two FDA-approved kinase inhibitors for non-oncological indications.
Definition
ChEBI: A pyrrolopyrimidine that is pyrrolo[2,3-d]pyrimidine substituted at position 4 by an N-methyl,N-(1-cyanoacetyl-4-methylpiperidin-3-yl)amino moiety. Used as its citrate salt to treat moderately to severely ctive rheumatoid arthritis.
Pharmacokinetics
Tofacitinib has good solubility (>4 mg/mL in water for the crystalline citrate salt), which contributes to its excellent oral bioavailability (74%) in healthy volunteers. However, tofacitinib exhibits relatively short elimination half-life of 3.2 hours, and its protein binding is very low (approximately 40%, predominantly to albumin). Tofacitinib undergoes major hepatic clearance (70% of total clearance) and minor renal clearance (30%). The metabolism of tofacitinib proceeds primarily in the liver by CYP3A4 (major) and CYP2C19 (minor), resulting in oxidation of the pyrrolopyrimidine and piperidine rings, oxidation of the piperidine ring side-chain, N-demethylation, and glucuronidation. As opposed to the longer half-life of biologics, small-molecule JAK inhibitors such as tofacitinib typically display much shorter half-lives with once or twice-daily dosing regimens, which may be inconvenient to some patients. However, the shorter half-life ensures faster recovery to the full ability to fight infections which may occur with any immune suppressing medication.
Clinical Use
Tofacitinib was approved for treating rheumatoid arthritis in 2012, joint pain and swelling, psoriatic arthritis in 2017, and ulcerative colitis in 2018. However, severe side effects observed during clinical studies prevented the FDA from approving more efficacious doses for the treatment of rheumatoid arthritis (RA). Tofacitinib also carries a black box warning for an increased risk of pulmonary embolism and death associated with the 10 mg BID dose.
Tofacitinib Preparation Products And Raw materials
Raw materials
Preparation Products
| Supplier | Tel | Country | ProdList | Advantage | Inquiry |
|---|---|---|---|---|---|
| Jigs Chemical ltd | +919099003427 | Gujarat, India | 239 | 58 | Inquiry |
| SEUTIC | +91-8309787199 +91-8309787199 | Hyderabad, India | 124 | 58 | Inquiry |
| Sekhment pharmaventures | +91-9030088669 +91-9030088669 | Mumbai, India | 105 | 58 | Inquiry |
| Kekule Pharma Limited | +919849798889 | Hyderabad, India | 59 | 58 | Inquiry |
| Aspen Biopharma Labs Pvt Ltd | +91-9248058660 +91-9248058662 | Telangana, India | 234 | 58 | Inquiry |
| CLEARSYNTH LABS LTD. | +91-22-45045900 | Hyderabad, India | 6257 | 58 | Inquiry |
| A.J Chemicals | 91-9810153283 | New Delhi, India | 6100 | 58 | Inquiry |
| SynZeal Research Pvt Ltd | +1 226-802-2078 | Gujarat, India | 6514 | 58 | Inquiry |
| Pharmaffiliates Analytics and Synthetics P. Ltd | +91-172-5066494 | Haryana, India | 6739 | 58 | Inquiry |
| Changsha Junyu Chemexpress.co., Ltd | +86-13723890100 | China | 134 | 58 | Inquiry |
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