Heinrich, Timo; Peterson, Carl; Schneider, Richard; Garg, Sakshi; Schwarz, Daniel; Gunera, Jakub; Seshire, Anita; Koetzner, Lisa; Schlesiger, Sarah; Musil, Djordje; Schilke, Heike; Doerfel, Benjamin; Diehl, Patrizia; Boepple, Pia; Lemos, Ana R.; Sousa, Pedro M. F.; Freire, Filipe; Bandeiras, Tiago M.; Carswell, Emma; Pearson, Nicholas; Sirohi, Sameer; Hooker, Mollie; Trivier, Elisabeth; Broome, Rebecca; Balsiger, Alexander; Crowden, Abigail; Dillon, Christian; Wienke, Dirk published the artcile< Optimization of TEAD P-Site Binding Fragment Hit into In Vivo Active Lead MSC-4106>, Recommanded Product: 3-Bromobenzotrifluoride, the main research area is pyrazoloindole carboxylic TEAD binding fragment hit lead.
The dysregulated Hippo pathway and, consequently, hyperactivity of the transcriptional YAP/TAZ-TEAD complexes is associated with diseases such as cancer. Prevention of YAP/TAZ-TEAD triggered gene transcription is an attractive strategy for therapeutic intervention. The deeply buried and conserved lipidation pocket (P-site) of the TEAD transcription factors is druggable. The discovery and optimization of a P-site binding fragment are described. Utilizing structure-based design, enhancement in target potency was engineered into the hit, capitalizing on the established X-ray structure of TEAD1. The efforts culminated in the optimized in vivo tool MSC-4106 (I), which exhibited desirable potency, mouse pharmacokinetic properties, and in vivo efficacy. In close correlation to compound exposure, the time- and dose-dependent downregulation of a proximal biomarker could be shown.
Journal of Medicinal Chemistry published new progress about Fused heterocyclic compounds Role: PAC (Pharmacological Activity), PKT (Pharmacokinetics), PRP (Properties), SPN (Synthetic Preparation), THU (Therapeutic Use), BIOL (Biological Study), PREP (Preparation), USES (Uses). 401-78-5 belongs to class bromides-buliding-blocks, and the molecular formula is C7H4BrF3, Recommanded Product: 3-Bromobenzotrifluoride.
Referemce:
Bromide – Wikipedia,
bromide – Wiktionary