Anthony Pinkerton, Ph.D.

Anthony Pinkerton

Anthony Pinkerton, Ph.D.

Director, Medicinal Chemistry
Director

Anthony Pinkerton's Research Focus

Techniques and Technology > Drug Discovery, Medicinal Chemistry, Synthetic Chemistry, Pharmacogenomics, Pharmacokinetics, Synthetic Organic Chemistry, Chemistry, Medicinal Chemistry, Synthetic Chemistry, Synthetic Organic Chemistry, Pharmacogenomics, Pharmacokinetics, Pharmacology
Related Diseases > Diabetes - General, Structural Biology, Cancer, Bone Mineralization Disorders, Cardiovascular Diseases, HIV/AIDS, Immune Disorders, Infectious Diseases, Inflammatory Bowel Disease, Malaria, Metabolic Diseases, Multiple Sclerosis, Neurodegenerative and Neuromuscular Diseases, Neurological and Psychiatric Disorders, Structural Biology
Research Models > Organic and Synthetic Chemistry, Organic and Synthetic Chemistry
Phenomena or Processes > Kinase Inhibitors, Nuclear Hormone Receptors, Organic/Synthetic/Medicinal Chemistry, Receptor Tyrosine Kinases, Tyrosine Kinases

Dr. Pinkerton is an experienced medicinal chemist, who leads MedChem efforts for the Prebys Center at SBP. He and his team drive screening hits to chemical probes or through lead optimization. Below are just a couple of examples of programs on which Tony and his team are currently working, or to which they have contributed. With a team of collaborators from Duke University Tony is leading the chemistry effort for the development of a novel series of NTR1 allosteric modulators, the first example of brain penetrant small molecule NTR1 activators that have been described. These first-in-class compounds are being optimized in to possible drug leads for the treatment of schizophrenia, drug abuse, and other neuropsychiatric disorders. In collaboration with Jose Luis Millan, a professor at SBP as well, Tony is leading the development of the first selective, potent and orally bioavailable tissue non specific alkaline phosphatase (TNAP) inhibitors that have shown strong efficacy in a range of animal models of pathological calcification. These inhibitors could have use in a range of disorders including vascular calcification, generalized arterial calcification of infancy (GACI), calciphylaxis and pseudoxanthoma elasticum (PXE). With a group of scientists from both UCSD and the University of Giessen in Germany, the SBP medicinal chemistry team has developed a series of remarkable potent and selective plasmodium falciparum G6PDH inhibitors as a potential treatment for resistant malaria. The lead compounds are currently in animal testing.

Anthony Pinkerton's Research Report

NTR1
 

ML314: A biased Neurotensin Receptor Ligan for Methamphetamine Abuse Barak, L.S.; Bai, Y.; Peterson, S.; Evron, T.; Urs, N. M.; Peddibhotla, S.; Hedrick, M. P.; Hershberger, P.; Maloney, P. R.; Chung, T. D. Y.; Rodriguiz, R. M.; Wetsel, W. C.; Thomas, J. B.; Hanson, G. R.; Pinkerton, A. B.; Caron, M. G. ACS Chemical Biology 2016

Peddibhotla, S.; Hedrick, M. P.; Hershberger, P.; Maloney, P. R.;  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, G. P.; Smith L. H.; Chung, T. D. Y; Hanson, G. R.; Thomas, J. B.; Caron, M. G.;  Barak, L. S.; Pinkerton, A. B.  (2013) “Discovery of ML314, a Brain Penetrant Non-Peptidic β-Arrestin Biased Agonist of the Neurotensin NTR1 Receptor” ACS Medicinal Chemistry Letters, 4, 846-851.  PMCID: PMC3940307.

Hershberger, P. M.; Hedrick, M. P.; Peddibhotla, S.; Mangravita-Novo, A.; Gosalia, P.; Li, Y.; Gray, W.; Vicchiarelli, M.; Smith, L. H.; Chung, T. D. Y.; Thomas, J. B.; Caron, M. G.; Pinkerton, A. B.; Barak, L. S.; Roth G. P. (2013) “Imidazole-derived agonists for the neurotensin 1 receptor” Bioorg. Med. Chem. Letters, Bioorg Med Chem Lett. 2014 Jan 1;24(1):262-7. doi: 10.1016/j.bmcl.2013.11.026. PMID: 24332089. PMCID: PMC3898338.

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 “Preparation of piperazinylquinazolines and related compounds as agonists of neurotensin receptor 1” Pinkerton, A.; Maloney, P.; Hershberger, S.; Peddibhotla, S.; Hedrick, M.; Barak, L.; Caron, M.

Sheffler, D. J., Pinkerton, A. B., Dahl, R.; Markou, A., Cosford, N. D. P. (2011) Recent Progress in the Synthesis and Characterization of Group II Metabotropic Glutamate Receptor Allosteric Modulators. ACS Chemical Neuroscience, 2 (8), 382–393. PMCID: PMC3369751.

TNAP
 

Pathophysiological role of vascular smooth muscle alkaline phosphatase in medial artery calcification” Sheen, C. R.; Kuss, P.; Narisawa, S.; Yadav, M. C.; Nigro, J.; Wang, W.; Chhea, T. N.; Sergienko, E. A.; Kapoor, K.; Jackson, M. R.; Hoylaerts, M. F.; Pinkerton, A. B.; O’Neill, W. C.; Millan, J. L.  Journal of Bone and Mineral Research2015, 30 (5), 824-836

Inhibitors of Tissue-Nonspecific Alkaline Phosphatase (TNAP): From Hits to Leads” Teriete, P.; Pinkerton, A. B.; Cosford, N. D. P., Methods in Molecular Biology,2013, 1053, 85-101

PCT WO 2016054056 “Methods of treating disorders characterized by medial vascular calcification with an inhibitor of tissue-nonspecific alkaline phosphatase” Gahl, W. A.; Ziegler, S. G.; Dietz, H. C.; Pinkerton, A. B.; Millan, J. L

PCT WO 2013126608 “Preparation of pyridinylsulfonamide derivatives for use as TNAP inhibitors” Pinkerton, A. B.; Dahl, R.; Cosford, N. D. P.; Millan, J. L

PfG6PDH
 

Discovery of a Plasmodium falciparum glucose-6-phosphate dehydrogenase 6-phosphogluconolactonase inhibitor (R,Z)-N-((1-ethylpyrrolidin-2-yl)methyl)-2-(2-fluorobenzylidene)-3-oxo-3,4-dihydro-2H-benzo[b][1,4]thiazine-6-carboxamide (ML276) that reduces parasite growth in vitro.” Preuss, J., Maloney, P., Peddibhotla, S., Hedrick, M. P., Hershberger, P., Gosalia, P., Milewski, M., Li, Y. L., Sugarman, E., Hood, B., Suyama, E., Nguyen, K., Vasile, S., Sergienko,E., Mangravita-Novo, A., Vicchiarelli, M., McAnally, M., Smith, L. H., Roth, G. P., Diwan, J., Chung, T. D. Y., Jortzik, E., Rahlfs, S., Becker, K., Pinkerton, A. B., Bode L. Journal of Medicinal Chemistry, 2012, 55 (16), 7262-7272

High-Throughput Screening for Small-Molecule Inhibitors of Plasmodium falciparum Glucose-6-Phosphate Dehydrogenase 6-Phosphogluconolactonase.”Preuss, J., Hedrick, M., Sergienko, E., Pinkerton, A., Mangravita-Novo, A., Smith, L., Marx, C., Fischer, E., Jortzik, E., Rahlfs, S, Becker, K., Bode, L. Journal of Biomolecular Screening 2012, 17 (6), 738-751

Anthony Pinkerton's Bio

Dr. Pinkerton’s career in industry began as a medicinal chemist at the Merck Research Laboratories in San Diego. Over his career, Tony has worked in multiple therapeutic areas including CNS, virology, diabetes, inflammation, and oncology, with extensive experience in GPCRs. He has been both project leader and project manager for oncology, virology and diabetes targets, as well as chemistry lead for the metabolic disease therapeutic area group, in which he helped a team identify and prosecute the most promising new targets in the field.

Tony has also performed due diligence for in-licensing efforts as well as competitive intelligence for multiple targets, in addition to developing IP strategies around multiple chemical series. He has extensive experience with outsourcing chemistry, both discovery and scale up, to China.

Tony is an inventor or co-inventor on over 35 patents or patent applications covering small molecule therapeutics, as well as over 50 publications. During his career he has helped advance multiple compounds into clinical development.

Tony originally trained as a synthetic organic chemist in the laboratories of Dieter Seebach at ETH-Zurich and Barry Trost at Stanford University. He earned his Ph.D. in chemistry from Stanford University in 2001. While at Stanford he developed new metal catalyzed reactions for synthesis and completed the total synthesis of several natural products. He was also a Fulbright Scholar at the Eidgenössische Technische Hochschule (ETH) – Zurich from 1995-1996.

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Publications

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
Dickey AS, Pineda VV, Tsunemi T, Liu PP, Miranda HC, Gilmore-Hall SK, Lomas N, Sampat KR, Buttgereit A, Torres MJ, Flores AL, Arreola M, Arbez N, Akimov SS, Gaasterland T, Lazarowski ER, Ross CA, Yeo GW, Sopher BL, Magnuson GK, Pinkerton AB, Masliah E, La Spada AR
Nat Med 2016 Jan;22(1):37-45
Ardecky RJ, Bobkova EV, Kiffer-Moreira T, Brown B, Ganji S, Zou J, Pass I, Narisawa S, Iano FG, Rosenstein C, Cheltsov A, Rascon J, Hedrick M, Gasior C, Forster A, Shi S, Dahl R, Vasile S, Su Y, Sergienko E, Chung TDY, Kaunitz J, Hoylaerts MF, Pinkerton AB, Millán JL
Bioorg Med Chem Lett 2014 Feb 1;24(3):1000-1004
Ziegler SG, Ferreira CR, MacFarlane EG, Riddle RC, Tomlinson RE, Chew EY, Martin L, Ma CT, Sergienko E, Pinkerton AB, Millán JL, Gahl WA, Dietz HC
Sci Transl Med 2017 Jun 7;9(393)
Masyuk TV, Masyuk AI, Lorenzo Pisarello M, Howard BN, Huang BQ, Lee PY, Fung X, Sergienko E, Ardesky RJ, Chung TD, Pinkerton AB, LaRusso NF
Hepatology 2017 May 23;
Shiryaev SA, Farhy C, Pinto A, Huang CT, Simonetti N, Ngono AE, Dewing A, Shresta S, Pinkerton AB, Cieplak P, Strongin AY, Terskikh AV
Antiviral Res 2017 Jul;143:218-229