Upadacitinib
- CAS No.
- 1310726-60-3
- Chemical Name:
- Upadacitinib
- Synonyms
- ABT-494;(3S,4R)-3-ethyl-4-(3H-imidazo[1,2-a]pyrrolo[2,3-e]pyrazin-8-yl)-N-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide;upatinib;Upadacitinib (ABT-494);benzyl (4S)-3-(N-(ethoxycarbonyl)-N-(5-tosyl-5H-pyrrolo[2,3-b]pyrazin-2-yl)glycyl)-4-ethylpyrrolidine-1-carboxylate;1-Pyrrolidinecarboxamide, 3-ethyl-4-(3H-imidazo[1,2-a]pyrrolo[2,3-e]pyrazin-8-yl)-N-(2,2,2-trifluoroethyl)-, (3S,4R)-;(3S,4R)-3-ethyl-4-(3H-imidazo[1,2-a]pyrrolo[2,3-e]pyrazin-8-yl)-N-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide, Upadacitinib;CS-2730;Upadacitinb;Upadacitinib
- CBNumber:
- CB53121345
- Molecular Formula:
- C17H19F3N6O
- Molecular Weight:
- 380.37
- MOL File:
- 1310726-60-3.mol
- MSDS File:
- SDS
- Modify Date:
- 2024/8/8 13:40:43
| Density | 1.56±0.1 g/cm3(Predicted) |
|---|---|
| storage temp. | Store at -20°C |
| solubility |
DMSO:42.67(Max Conc. mg/mL);112.17(Max Conc. mM) DMSO:PBS (pH 7.2) (1:1):0.5(Max Conc. mg/mL);1.31(Max Conc. mM) DMF:30.0(Max Conc. mg/mL);78.87(Max Conc. mM) Ethanol:76.0(Max Conc. mg/mL);199.8(Max Conc. mM) |
| form | A crystalline solid |
| pka | 11.89±0.60(Predicted) |
| color | White to off-white |
| InChI | InChI=1S/C17H19F3N6O/c1-2-10-7-25(16(27)24-9-17(18,19)20)8-11(10)13-5-22-14-6-23-15-12(26(13)14)3-4-21-15/h3-6,10-11,21H,2,7-9H2,1H3,(H,24,27)/t10-,11+/m1/s1 |
| InChIKey | WYQFJHHDOKWSHR-MNOVXSKESA-N |
| SMILES | N1(C(NCC(F)(F)F)=O)C[C@H](C2N3C4C=CNC=4N=CC3=NC=2)[C@H](CC)C1 |
SAFETY
Risk and Safety Statements
| Symbol(GHS) |  GHS07 |
|---|---|
| Signal word | Warning |
| Hazard statements | H302 |
| Precautionary statements | P280-P305+P351+P338 |
Upadacitinib Chemical Properties,Uses,Production
Characteristics
Class: non-receptor tyrosine kinase
Treatment: psoriatic arthritis, rheumatoid arthritis
Elimination half-life = 6–16 h
Protein binding = 52%
Uses
Upadacitinib also known as ABT-494, is a potent and selective Janus kinase (JAK) 1 inhibitor being developed for the treatment of several autoimmune disorders, Janus kinase inhibitors for rheumatoid arthritis. It is used to treat moderate to severely active rheumatoid arthritis, active psoriatic arthritis, ankylosing spondylitis, non-radiographic axial spondyloarthritis (a type of arthritis in the spine) with objective signs of swelling, moderate to severe ulcerative colitis, and moderate to severe Crohn's disease in patients who have taken other medicines (eg, methotrexate) that did not work well. It is also used to treat moderate to severe atopic dermatitis (eczema) in patients who have taken other medicines that did not work well and whose condition is not well controlled with other treatments or in patients who cannot tolerate these treatments. It is also used to treatpsoriatic arthritis, axial SpA and Giant Cell Arteritis and Takayasu Arteritis.
brand name
Upadacitinib is marketed under the brand name RINVOQ for oral administration.
Biological Activity
Upadacitinib is a potent, orally active and selective Janus kinase 1 (JAK1) inhibitor (IC50=43 nM). Upadacitinib displays approximately 74 fold selective for JAK1 over JAK2 (200 nM) in cellular assays dependent on specific, relevant cytokines. Upadacitinib can be used for several autoimmune disorders research. In vivo, Upadacitinib inhibited paw swelling and bone destruction in a rat model of arthritis.
Mechanism of action
The Janus kinases (JAKs) are a family of cytoplasmic tyrosine kinases whose function is to transduce cytokine-mediated signals via the JAK-STAT pathway. There are four JAK subtypes, each of which has overlapping receptor responsibilities. Inhibitors of this enzyme family (jakinibs) have shown efficacy in treating certain inflammatory and autoimmune diseases such as rheumatoid arthritis and Crohn's disease. However, the first generation of these drugs, tofacitinib and ruxolitinib, lacked subtype selectivity, affecting JAK1/JAK3 and JAK1/JAK2 respectively. This has led to dose-limiting side effects in this otherwise promising class of drugs. Upadacitinib is a second generation Janus kinase inhibitor that is selective for the JAK1 subtype of this enzyme over the JAK2 (74-fold), JAK3 (58-fold) and tyrosine kinase 2 subtypes.
Clinical Use
Upadacitinib is indicated for the treatment of moderate to severe active rheumatoid arthritis in adults who have responded inadequately to, or who are intolerant to one or more disease-modifying antirheumatic drugs (DMARDs). Upadacitinib may be used as monotherapy or in combination with methotrexate.
Side effects
Common side effects are upper respiratory tract infections such as common cold and sinus infections (13.5% of patients in studies), nausea (3.5%), cough (2.2%), fever, and increased liver enzymes. Serious side effects include infections, including life-threatening ones, such as pneumonia, cellulitis, tuberculosis, as well as shingles and other herpes infections.
Metabolism
Upadacitinib displays a dose-proportional pharmacokinetic profile over the therapeutic dose range. Following oral administration, the median time to reach Cmax (Tmax) ranges from 2 to 4 hours. The steady-state plasma concentrations of upadacitinib are reached within 4 days following multiple once-daily administrations, with minimal accumulation. Food intake has no clinically relevant effect on the AUC, Cmax, and Cmin of upadacitinib from the extended-release formulation. Upadacitinib metabolism is mainly mediated by CYP3A4, with a potential minor contribution from CYP2D6. Administration of strong CYP3A inhibitors increases upadacitinib AUC by 75% and Cmax by 70%, while strong inducers of CYP3A reduce upadacitinib plasma exposures by approximately half[1].
References
[1] Mohamed-Eslam F. Mohamed. “Upadacitinib: Mechanism of action, clinical, and translational science.” Cts-Clinical and Translational Science 17 1 (2023).
Upadacitinib Preparation Products And Raw materials
Raw materials
Preparation Products
| Supplier | Tel | Country | ProdList | Advantage | Inquiry |
|---|---|---|---|---|---|
| Venkatasai Life Sciences | +91-9908134868 +91-8008303069 | Hyderabad, India | 186 | 58 | Inquiry |
| A.J Chemicals | 91-9810153283 | New Delhi, India | 6124 | 58 | Inquiry |
| CLEARSYNTH LABS LTD. | +91-22-45045900 | Hyderabad, India | 6351 | 58 | Inquiry |
| Pharmaffiliates Analytics and Synthetics P. Ltd | +91-172-5066494 | Haryana, India | 6773 | 58 | Inquiry |
| SynZeal Research Pvt Ltd | +1 226-802-2078 | Gujarat, India | 6522 | 58 | Inquiry |
| Shanghai Rochi Pharmaceutical Co.,Ltd. | 21-38751876 +8615000076078 | China | 431 | 58 | Inquiry |
| Beijing Mesochem Technology Co.,Ltd | +8613651027935 | China | 191 | 58 | Inquiry |
| TAIZHOU YUXIN BIOTECHNOLOGY CO,.LTD | +86-576-88902229;+86-0576-88902229 +8613968687450 | China | 158 | 58 | Inquiry |
| Wuhan Topule Biopharmaceutical Co., Ltd | +8618327326525 | China | 8474 | 58 | Inquiry |
| SHANDONG BOYUAN PHARMACEUTICAL CO., LTD. | +86-0531-69954981 +8615666777973 | China | 211 | 58 | Inquiry |
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