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Prebys Center

Neurotensin Receptor 1 (NTR1) Research Program

 

Neurotensin (NT), a neuropeptide that acts as a regulator of many important systems including the dopaminergic system, has a broad spectrum of physiological activities: acting as a neurotransmitter in the brain; behaving as a digestive hormone in the gut; and acting as a regulator of cardiac output and blood pressure in the cardiovascular system. Therapeutic rationale have been proposed for brain penetrant NTR1 (neurotensin receptor 1) agonists for the treatment of schizophrenia, addiction and obesity, and indeed, an increasing body of preclinical and clinical evidence supports the promise of NT analogs as therapeutic agents for schizophrenia, psychostimulant abuse, and obesity. Our NTR1 research program was born from a collaboration with Duke University researchers Larry Barak and Marc Caron. Funding from NIH’s Molecular Libraries Program stimulated our initial investigations, which have continued through other mechanisms.

 

Patents

PCT WO 2015200534 “Preparation of substituted quinazolines as small molecule agonists of neurotensin receptor 1” Pinkerton, A. B.; Hershberger, P. M.; Peddibhotla, S.; Maloney, P. R.; Hedrick, M. P.

PCT WO 2014100501 “Small Molecule Agonists Of Neurotensin Receptor 1” Pinkerton, A.; Maloney, P.; Hershberger, P.; Peddibhotla, S.; Hedrick, M.; Barak, L.; Caron, M.

Grant

Lead optimization of brain penetrant Neurotensin Receptor 1 agonists, Anthony Pinkerton Renewed as an R33 development award

Drug Abuse: Discovering Ligands for Pertinent GPCRs , Collaboration with Marc Caron at Duke University and Anthony Pinkerton at SBP

Small Molecule Agonsists for the Neurotensin 1 Receptor, Collaboration with Lawrence Barak at Duke University and Anthony Pinkerton at SBP

Publications

Hershberger P, Hedrick M, Peddibhotla S, Maloney P, Li Y, Milewski M, Gosalia P, Gray W, Mehta A, Sugarman E, Hood B, Suyama E, Nguyen K, Heynen-Genel S, Vasile S, Salaniwal S, Stonich D, Su Y, Mangravita-Novo A, Vicchiarelli M, Smith LH, Roth G, Diwan J, Chung TDY, Caron MG, Thomas JB, Pinkerton AB, Barak LR
2010;
Peddibhotla S, Hedrick MP, Hershberger P, Maloney PR, Li Y, Milewski M, Gosalia P, Gray W, Mehta A, Sugarman E, Hood B, Suyama E, Nguyen K, Heynen-Genel S, Vasile S, Salaniwal S, Stonich D, Su Y, Mangravita-Novo A, Vicchiarelli M, Roth GP, Smith LH, Chung TD, Hanson GR, Thomas JB, Caron MG, Barak LS, Pinkerton AB
ACS Med Chem Lett 2013 Jul 20;4(9):846-851
Barak LS, Bai Y, Peterson S, Evron T, Urs NM, Peddibhotla S, Hedrick MP, Hershberger P, Maloney PR, Chung TD, Rodriguiz RM, Wetsel WC, Thomas JB, Hanson GR, Pinkerton AB, Caron MG
ACS Chem Biol 2016 Jul 15;11(7):1880-90