Juq-139 Jun 2026

Our group previously identified a 1,3‑benzothiazole‑based series (compound series ) that displayed modest PI3K‑α inhibition (K i ≈ 120 nM) but suffered from poor metabolic stability (Patel et al., 2021). In an effort to improve potency, selectivity, and pharmacokinetic (PK) properties, we pursued a hybrid design merging the benzothiazole core with a pyrazolo[1,5‑a]pyridine fragment, a privileged motif known to enhance kinase binding through a hinge‑region hydrogen bond (Wang et al., 2018). The resulting molecule, JUQ‑139 , incorporates a sulfonamide tether bearing a para‑fluorophenyl‑propyl side chain to improve oral absorption and metabolic stability.