Juq-565 [upd] Review

JUQ‑565 emerged from a phenotypic screen of ~2 × 10⁶ small molecules designed to suppress Akt phosphorylation in a PIK3CA ‑mutant TNBC line (MDA‑MB‑468). Preliminary hits exhibited a quinazolinone‑pyridine core, prompting a focused SAR campaign that culminated in JUQ‑565 (Figure 1). The molecule combines a 4‑fluorophenyl substituent at the quinazolinone C‑2 position with a 2‑pyridyl‑methyl side chain, conferring high affinity for the ATP‑binding pocket of PI3Kα while minimizing off‑target kinase interactions.

2‑Aminobenzamide (1.0 eq) was condensed with 4‑fluorobenzoyl chloride (1.2 eq) in dry dichloromethane (DCM) in the presence of triethylamine (2 eq) at 0 °C → rt (4 h). Cyclization was achieved by heating the crude amide in polyphosphoric acid (PPA) at 120 °C for 2 h, affording the quinazolinone core (95 % yield). JUQ-565

In biotech or medical fields, it could signify a new drug candidate, a genetic marker, or any innovative therapeutic approach. JUQ‑565 emerged from a phenotypic screen of ~2

“Old Harbor, berth nine,” Mara said. She let the ship take the route, not the fastest but the one with fewer eyes. 2‑Aminobenzamide (1

Tumor biopsies harvested 4 h after the first dose were analyzed for p‑Akt and γ‑H2AX (DNA damage marker) by immunohistochemistry.

¹Department of Chemical Biology, University of Cambridge, United Kingdom ²Institute for Molecular Medicine, Seoul National University, South Korea ³Centro de Investigación Biomédica, Universidad de Buenos Aires, Argentina ⁴Department of Oncology, Stanford University School of Medicine, USA ⁵Division of Pharmacology, Indian Institute of Science, Bengaluru, India