Juq-279
The JUQ-279: Unveiling the Mysteries of a Unique Research Chemical
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Objective: To synthesize, biochemically characterize, and evaluate the anti‑tumor efficacy of JUJ‑279 (hereafter JUQ‑279), a novel, orally bioavailable, ATP‑competitive inhibitor of class‑I PI3K isoforms with preferential activity against the p110β subunit. JUQ-279
Methods: JUQ‑279 was synthesized via a convergent palladium‑catalyzed cross‑coupling route. In vitro kinase profiling (Eurofins DiscoverX) determined selectivity across 468 kinases. Cellular potency was measured in a panel of 12 TNBC cell lines (IC₅₀ values via CellTiter‑Glo). Mechanistic assays included phospho‑Western blotting, apoptosis (Annexin V/PI), cell‑cycle analysis (flow cytometry), and RNA‑seq for pathway modulation. In vivo efficacy and pharmacokinetics were assessed in orthotopic MDA‑MB‑231 xenografts (N = 10/group) and a patient‑derived xenograft (PDX) cohort (N = 6/group). Toxicology was performed in CD‑1 mice (28‑day repeat dose). The JUQ-279: Unveiling the Mysteries of a Unique