Chemical Probe Identification Platform for Orphan GPCRs Using Focused Compound Screening: GPR39 as a Case Example was written by Boehm, Markus;Hepworth, David;Loria, Paula M.;Norquay, Lisa D.;Filipski, Kevin J.;Chin, Janice E.;Cameron, Kimberly O.;Brenner, Martin;Bonnette, Peter;Cabral, Shawn;Conn, Edward;Ebner, David C.;Gautreau, Denise;Hadcock, John;Lee, Esther C. Y.;Mathiowetz, Alan M.;Morin, Michelle;Rogers, Lucy;Smith, Aaron;VanVolkenburg, Maria;Carpino, Philip A.. And the article was included in ACS Medicinal Chemistry Letters in 2013.Name: 6-(Piperazin-1-yl)nicotinonitrile This article mentions the following:
Orphan G protein-coupled receptors (oGPCRs) are a class of integral membrane proteins for which endogenous ligands or transmitters have not yet been discovered. Transgenic animal technologies have uncovered potential roles for many of these oGPCRs, providing new targets for the treatment of various diseases. Understanding signaling pathways of oGPCRs and validating these receptors as potential drug targets requires the identification of chem. probe compounds to be used in place of endogenous ligands to interrogate these receptors. A novel chem. probe identification platform was created in which GPCR-focused libraries were screened against sets of oGPCR targets, with a goal of discovering fit-for-purpose chem. probes for the more druggable members of the set. Application of the platform to a set of oGPCRs resulted in the discovery of the first reported small mol. agonists for GPR39, a receptor implicated in the regulation of insulin secretion and preservation of beta cells in the pancreas. Compound 1 stimulated intracellular calcium mobilization in recombinant and native cells in a GPR39-specific manner but did not potentiate glucose-stimulated insulin secretion in human islet preparations In the experiment, the researchers used many compounds, for example, 6-(Piperazin-1-yl)nicotinonitrile (cas: 149554-29-0Name: 6-(Piperazin-1-yl)nicotinonitrile).
6-(Piperazin-1-yl)nicotinonitrile (cas: 149554-29-0) belongs to piperazine derivatives. A form in which piperazine is commonly available industrially is as the hexahydrate, C4H10N2. 6H2O, which melts at 44 °C and boils at 125–130 °C. Two common salts in the form of which piperazine is usually prepared for pharmaceutical or veterinary purposes are the citrate, 3C4H10N2.2C6H8O7 (i.e. containing 3 molecules of piperazine to 2 molecules of citric acid), and the adipate, C4H10N2.C6H10O4 (containing 1 molecule each of piperazine and adipic acid).Name: 6-(Piperazin-1-yl)nicotinonitrile
Referemce:
Piperazine – Wikipedia,
Piperazines – an overview | ScienceDirect Topics