Upadacitinib CAS No. 1310726-60-3

Uses

• Indications:

  • Rheumatoid Arthritis: For moderately to severely active rheumatoid arthritis in adult patients who have had an inadequate response or intolerance to one or more disease-modifying antirheumatic drugs (DMARDs).

  • Psoriatic Arthritis: For active psoriatic arthritis in adult patients who have had an inadequate response or intolerance to one or more DMARDs.

  • Ankylosing Spondylitis: For active ankylosing spondylitis or radiographic axial spondyloarthritis in adult patients who have had an inadequate response to conventional therapy.

  • Ulcerative Colitis: For moderately to severely active ulcerative colitis in adults who have had an inadequate response or intolerance to either conventional therapy or a biologic agent.

  • Crohn's Disease: For moderately to severely active Crohn's disease in adults who have had an inadequate response or intolerance to one or more TNF blockers.

  • Atopic Dermatitis: For moderate to severe atopic dermatitis in adults and children 12 years and older who are candidates for systemic therapy.

• Other Uses:

  • Sweet Syndrome: Successfully used to treat chronic steroid-dependent Sweet syndrome, highlighting its potential in refractory cases.

  • Inflammatory Bowel Disease (IBD): Demonstrated efficacy in maintaining clinical remission and endoscopic response in patients with Crohn's disease.

Mechanism of Action

• Selective JAK1 Inhibition: Upadacitinib is a selective inhibitor of Janus kinase 1 (JAK1), which plays a crucial role in the signaling pathways of many cytokines and growth factors involved in immune and inflammatory responses. By inhibiting JAK1, upadacitinib reduces the activation of signal transducers and activators of transcription (STATs), thereby reducing inflammation.

Properties and Characteristics

• Chemical Name: Upadacitinib

• Preferred InChI Key: WYQFJHHDOKWSHR-MNOVXSKESA-N

• Synonyms:

  • Upadacitinib

  • (3S,4R)-3-ethyl-4-(1,5,7,10-tetraazatricyclo(7.3.0.0^(2,6))dodeca-2(6),3,7,9,11-pentaen-12-yl)-N-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide

  • (3S,4R)-3-ethyl-4-(3H-imidazo(1,2-a)pyrrolo(2,3-e)pyrazin-8-yl)-N-(2,2,2-trifluoroethyl)-1-pyrrolidinecarboxamide

  • 4RA0KN46E0

  • Abt-494

  • DTXCID401513480

  • DTXSID901027919

  • L04AA44

  • RefChem:57163

  • Upadacitinib anhydrous

  • Upadacitinibum

  • 1310726-60-3

• CAS Registry Number: 1310726-60-3

• UNII: 4RA0KN46E0

• MeSH Entry Terms: Upadacitinib, (3S,4R)-3-ethyl-4-(3H-imidazo(1,2-a)pyrrolo(2,3-e)pyrazin-8-yl)-N-(2,2,2-trifluoroethyl)-1-pyrrolidinecarboxamide, ABT-494

• Preferred InChI Key: WYQFJHHDOKWSHR-MNOVXSKESA-N

• Boiling Point: 189°C

• Melting Point: 16-19°C

• Solubility: Soluble in water

• Protein Binding: 52% bound to human plasma proteins

• Metabolism: Predominantly metabolized by CYP3A4; also metabolized by CYP2D6 to a lesser extent

• Excretion: Approximately 53% excreted in feces, 43% excreted in urine

• Half-Life: 8 to 14 hours

• Volume of Distribution: 224 L (in a patient with rheumatoid arthritis and a body weight of 74 kg)

Safety and Side Effects

• Common Side Effects:

  • Upper respiratory tract infections

  • Nausea

  • Elevated liver enzymes

  • Fever

  • Cough

• Serious Side Effects:

  • Serious infections

  • Herpes zoster virus infections

  • Malignancies

  • Major adverse cardiovascular events (MACE)

  • Gastrointestinal perforations

• Pregnancy and Lactation:

  • Avoided during pregnancy and breastfeeding due to potential teratogenicity and unknown effects on the infant's immune system.

• Drug Interactions:

  • Use with caution when co-administered with strong CYP3A4 inhibitors or inducers, as it may alter drug plasma concentrations.

Regulatory Approvals

• FDA Approval: August 2019

• European Commission Approval: December 2019

• Health Canada Approval: December 2019

Product Documents

• Safety Data Sheet (SDS)
• Certificate of Analysis
• Product Brochure
• Technical Data Sheet