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Discovery and characterization of 2-(cyclopropanesulfonamido)-N-(2-ethoxyphenyl)benzamide, ML382: a potent and selective positive allosteric modulator of MrgX1

, : Discovery and characterization of 2-(cyclopropanesulfonamido)-N-(2-ethoxyphenyl)benzamide, ML382: a potent and selective positive allosteric modulator of MrgX1. Chemmedchem 10(1): 57-61

Previous studies have shown that the activation of mouse MrgC11, a G-protein-coupled receptor, by its peptide ligand BAM8-22 can inhibit chronic pain. A large-scale screen has been carried out to isolate small-molecule allosteric agonists of MrgX1, the human homologue of MrgC11. The goal of this study is to improve the efficacy and potency of positive allosteric modulators (PAMs) with therapeutic implications in combating chronic pain. Herein we report an iterative parallel synthesis effort and a structure-activity relationship study of a series of arylsulfonamides which led to the discovery of the first PAM of MrgX1, ML382.


PMID: 25209672

DOI: 10.1002/cmdc.201402277

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Cervia, D.; Fehlmann, D.; Hoyer, D., 2003: Native somatostatin sst2 and sst5 receptors functionally coupled to Gi/o-protein, but not to the serum response element in AtT-20 mouse tumour corticotrophs. Of the five cloned somatostatin (SRIF: somatotropin release inhibitory factor) receptors (sst1-5), only sst2 and sst5 receptors appear to be endogenously expressed and functionally active in AtT-20 mouse anterior pituitary tumour cells. In this st...

Anonymous, 1959: THE CHLOROTHIAZIDES and potassium. British Medical Journal 1(5137): 1579-1580

Storey, K.B., 1978: Purification and properties of fructose diphosphatase from bumblebee flight muscle. Role of the enzyme in control of substrate cycling. Groups of Bombus terrestris that had been: (1) flying for 1-2 min at 21 deg C, (2) resting for 20 min at 21 deg , or (3) resting for 20 min at 5 deg , were killed and quick-frozen. Fructose diphosphatase in the flight muscles was then extracted an...

Leggewie Wilhelm; Schonefeld W., 1960: Die Flora der Homoceras-Zone in den untersten Grenzschichten der Herzkamper Mulde. Defines the lithologic and faunal facies of a continuous sequence of six lowermost upper Carboniferous ammonite zones exposed on the south flank of the Herzkamp basin, Germany. The plant assemblage is analogous to that in the lower Namurian of Bel...

Devaux, Henri, 1947: The intercellular spaces of the higher plants and their significance. In the embryo or any vegetative point of a higher plant without any differentiated vessels there is nevertheless a complete system of spaces, showing that this air-carrying system is contemporary with the formation of the tissues, while in the low...

Rawlings, D.E., 2002: Heavy metal mining using microbes. The use of acidiphilic, chemolithotrophic iron- and sulfur-oxidizing microbes in processes to recover metals from certain types of copper, uranium, and gold-bearing minerals or mineral concentrates is now well established. During these processes i...

Duffy, T.H.; Onishi, H.; Schall, R.F.Jr, 1996: Evaluation of a liquid therapeutic drug monitoring control. Clinical Chemistry 42(6 PART 2): S221

Desikan, R.S.; McEvoy, L.K.; Thompson, W.K.; Holland, D.; Brewer, J.B.; Aisen, P.S.; Sperling, R.A.; Dale, A.M.; Weiner, M.; Aisen, P.; Weiner, M.; Aisen, P.; Petersen, R.; Jack, C.R.; Jagust, W.; Trojanowki, J.Q.; Toga, A.W.; Beckett, L.; Green, R.C.; Saykin, A.J.; Morris, J.; Liu, E.; Green, R.C.; Montine, T.; Petersen, R.; Aisen, P.; Gamst, A.; Thomas, R.G.; Donohue, M.; Walter, S.; Gessert, D.; Sather, T.; Beckett, L.; Harvey, D.; Gamst, A.; Donohue, M.; Kornak, J.; Jack, C.R.; Dale, A.; Ber, 2012: Amyloid-β--associated clinical decline occurs only in the presence of elevated P-tau. To elucidate the relationship between the 2 hallmark proteins of Alzheimer disease (AD), amyloid-(Aβ) and tau, and clinical decline over time among cognitively normal older individuals. A longitudinal cohort of clinically and cognitively normal o...

Lamke, L.O., 1970: An instrument for estimating evaporation from small skin surfaces. Scandinavian Journal of Plastic and Reconstructive Surgery 4(1): 1-7

Stephen, W.; Shock, C.; Willnow, J.S.isher, J.S.ieber, T., 1987: Management factor interactions on alfalfa seed production. Special report Oregon State University Agricultural Experiment Station: (814) 25-30