Identification of an Orally Bioavailable Quinoline-Based Small-Molecule Tumor Necrosis Factor α (TNF-α) Inhibitor Featuring a Spirocyclic Scaffold - PubMed
6 hours ago
- #TNF-α inhibitor
- #quinoline scaffold
- #rheumatoid arthritis
- A series of quinoline-based small molecules with spirocyclic scaffolds were designed as TNF-α inhibitors for autoimmune diseases like rheumatoid arthritis.
- Compound XS-18 showed strong binding affinity to TNF-α (FP IC50 = 123 nM; KD = 45.9 nM) and inhibited TNF-α mediated inflammatory pathways in vitro.
- In a collagen-induced arthritis mouse model, oral XS-18 had strong anti-inflammatory effects and promoted joint cartilage repair better than tofacitinib.
- XS-18 exhibited favorable pharmacokinetic properties, including a half-life of 7.1 hours and oral bioavailability of 56.8%.
- XS-18 is a promising oral small-molecule TNF-α inhibitor for treating autoimmune diseases due to its efficacy and bioavailability.