Upadacitinib

Description: Upadacitinib (ABT-494) is a drug which is currently under investigation for the treatment of rheumatoid arthritis, Crohn's disease, ulcerative colitis, and psoriatic arthritis.

• Catalog: OFC1310726603-1
• CAS: 1310726-60-3
• Category: Fluorinated APIs
• Synonyms: ABT-494
• Purity: 98%
• MDL Number: MFCD30502663

• IUPAC Name: (3S,4R)-3-ethyl-4-(1,5,7,10-tetrazatricyclo[7.3.0.02,6]dodeca-2(6),3,7,9,11-pentaen-12-yl)-N-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide
• 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
• InChI Key: WYQFJHHDOKWSHR-MNOVXSKESA-N
• Isomeric SMILES: CC[C@@H]1CN(C[C@@H]1C2=CN=C3N2C4=C(NC=C4)N=C3)C(=O)NCC(F)(F)F

• Molecular Formula: C17H19F3N6O
• Molecular Weight: 380.38
• Molar Refractivity: 96.54
• Appearance: White to off-white solid powder

• XLogP3-AA: 2.7
• Hydrogen Bond Donor Count: 2
• Hydrogen Bond Acceptor Count: 6
• Rotatable Bond Count: 3
• Exact Mass: 380.15724374 g/mol
• Monoisotopic Mass: 380.15724374 g/mol
• Topological Polar Surface Area: 78.3Ų
• Heavy Atom Count: 27
• Formal Charge: 0
• Complexity: 561
• Bioavailability Score: 0.55
• Egan: 0.0
• Ghose: None
• Lipinski: 0.0
• Muegge: 0.0
• Veber: 0.0
• Consensus LogP: 2.48
• MLogP: 1.63
• SILICOS-IT: 1.76
• WLogP: 3.79
• XLogP3: 2.69
• iLogP: 2.55
• BBB Permeant: No
• CYP1A2 Inhibitor: Yes
• CYP2C19 Inhibitor: Yes
• CYP2C9 Inhibitor: No
• CYP2D6 Inhibitor: Yes
• CYP3A4 Inhibitor: No
• GI Absorption: High
• LogKp: -6.71 cm/s
• P-gp Substrate: Yes
• Fraction Csp3: 0.47

• GHS Pictogram: GHS07
• Hazard Statements: H302
• Precautionary Statements: P280-P305+P351+P338

Case Study

Upadacitinib for Assessment of Placental Transfer and Breast Milk Excretion in Lactating Women with IBD

Duricova D, et al. Clinical Gastroenterology and Hepatology, 2025.

This case study investigated the pharmacokinetics of upadacitinib in lactating women with inflammatory bowel disease (IBD) to evaluate placental transfer and breast milk excretion. Four participants received induction (45 mg/day) or maintenance (30 mg/day) doses. Milk samples (n = 40) were collected 1-24 h post-dose, and plasma from a mother-infant pair at delivery assessed placental transfer. Milk concentrations were analyzed via the trapezoidal method to calculate area under the concentration-time curve (AUC), daily infant dosage (DID), and relative infant dose (RID). Upadacitinib was detectable in all samples, with peak milk levels 4-5 h post-dose. Infant-to-maternal plasma ratios indicated moderate placental transfer (0.44). This study provides experimental data critical for evaluating upadacitinib safety in breastfeeding contexts.

Upadacitinib for the Experimental Modulation of Dermal Fibrosis via JAK1 Inhibition

Koçak A, et al. Toxicology in Vitro, 2025, 107, 106078.

This study evaluates the experimental application of Upadacitinib in attenuating dermal fibrosis and inflammation. Using a bleomycin-induced systemic sclerosis (SSc) mouse model and primary human lung fibroblasts (CCL-191 cells), Upadacitinib was administered individually and in combination with the PD29 peptide. Western blotting quantified protein levels of collagen-1, α-SMA, and JAK1, while RT-qPCR assessed mRNA expression of α-SMA, JAK1, TGF-β1, STAT3, and collagen-1. Serum IL-6 levels were measured to evaluate systemic inflammation. Results demonstrated significant downregulation of fibrotic and inflammatory markers and reduced collagen deposition, highlighting Upadacitinib's experimental efficacy in modulating TGF-β/Smad and JAK signaling pathways in fibrosis models.

Upadacitinib for the Long-Term Management of Moderately to Severely Active Ulcerative Colitis: An Experimental Application Study

Panaccione PR, et al. The Lancet Gastroenterology & Hepatology, 2025, 10(6), 507-519.

This study evaluated the long-term efficacy and safety of upadacitinib in patients with moderately to severely active ulcerative colitis using a phase 3, 288-week, multicenter, long-term extension (U-ACTIVATE) protocol. Eligible patients achieving clinical response in 8-week upadacitinib 45 mg induction and completing 52-week maintenance were enrolled. Patients received upadacitinib 15 mg or 30 mg, with dose escalation applied per remission status. Key experimental endpoints included clinical remission and endoscopic remission, assessed via adapted Mayo scores at weeks 48 and 96. Safety outcomes encompassed treatment-emergent and serious adverse events. As-observed analyses demonstrated sustained clinical and endoscopic remission, highlighting upadacitinib's experimental application in long-term ulcerative colitis therapy with a favorable risk-benefit profile.