500013-41-2Relevant academic research and scientific papers
From PARP1 to TNKS2 inhibition: A structure-based approach
Tomassi, Stefano,Pfahler, Julian,Mautone, Nicola,Rovere, Annarita,Esposito, Chiara,Passeri, Daniela,Pellicciari, Roberto,Novellino, Ettore,Pannek, Martin,Steegborn, Clemens,Paiardini, Alessandro,Mai, Antonello,Rotili, Dante
, p. 862 - 868 (2020)
Tankyrases (TNKSs) have recently gained great consideration as potential targets in Wnt/β-catenin pathway-dependent solid tumors. Previously, we reported the 2-mercaptoquinazolin-4-one MC2050 as a micromolar PARP1 inhibitor. Here we show how the resolution of the X-ray structure of PARP1 in complex with MC2050, combined with the computational investigation of the structural differences between TNKSs and PARP1/2 active sites, provided the rationale for a structure-based drug design campaign that with a limited synthetic effort led to the discovery of the bis-quinazolinone 5 as a picomolar and selective TNKS2 inhibitor, endowed with antiproliferative effects in a colorectal cancer cell line (DLD-1) where the Wnt pathway is constitutively activated.
benzamide derivatives as oxytocin agonists and vasopressin antagonists
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Page 34, (2010/02/08)
Novel compounds according to general formula 1, wherein G1 is NR5R6 or a fused polycyclic group that are specific OT receptor agonists and/or Via receptor antagonists. Pharmaceutical compositions comprising such compounds are useful in the treatment of, inter alia, primary dysmenorrhoea.
