Jon E. Hawkinson, PhD

My research focuses on the identification of compounds for lead optimization drug discovery in all therapeutic areas. I am particularly interested in new treatments for CNS disorders, particularly in the pain therapeutic area. I have 20 years of experience leading in vitro pharmacology teams in biopharmaceutical companies and academia, with particular expertise in biochemical, cellular, and molecular pharmacology, assay development, HTS, phenotypic screening, fragment-based screening, SAR, lead discovery and optimization, and drug discovery. I am currently collaborating with Professor Phil Portoghese to identify a development candidate acting at opioid heterodimers with an improved side effect profile to treat chronic pain. At Elan Pharmaceuticals, I led project teams that identified two development candidates for pain, including the anti-nerve growth factor (NGF) monoclonal antibody MEDI-578, which entered Phase 1 clinical trials, and the small molecule bradykinin B1 receptor antagonist ELN441958. I contributed to the discovery of three development candidates that entered Phase 1 trials, including the y-secretase development candidates ELND006 and ELND007 for Alzheimer’s Disease and the GABAA receptor positive allosteric modulator development candidate CCD3693 for insomnia. I also contributed to the development of licostinel (entered Phase I trials for stroke), ganaxolone (in Phase II for status epilepticus), and brilaroxazine (in Phase II trials for schizophrenia). I am the author of over 60 original research publications and five issued US patents.

• High-throughput screening
• Assay development
• Neuroscience
• Pharmacology
• Lead optimization
• Drug discovery

PubMed

P. Kalra, L. McGraw, J.R. Kimbrough, A.K. Pandey, J. Solberg, H. Cui, A. Divakaran, K. John, J.E. Hawkinson, W.C.K. Pomerantz. Quantifying the selectivity of protein-protein and small molecule interactions with fluorinated tandem bromodomain reader proteins. ACS Chem. Biol.15:3038-3049, 2020.

E. Akgün, M.M. Lunzer, D. Tian, M. Ansonoff, J. Pintar, D. Bruce, J.E. Hawkinson, G.L. Wilcox, P.S. Portoghese. FBNTI, a DOR-selective antagonist that allosterically activates MOR within a MOR-DOR heteromer. Biochemistry Online ahead of print, Sep 20, 2020.

E.B. Faber, D. Tian,D. Burban, N.M. Levinson,J.E. Hawkinson,G.I. Georg. Cooperativity between orthosteric inhibitors and allosteric inhibitor 8-anilino-1-naphthalene sulfonic acid (ANS) in cyclin-dependent kinase 2 (Cdk2). ACS Chem. Biol. 15:1759-1764, 2020.

M.V. Green, T. Pengo, J.D. Raybuck, T. Naqvi, H. McMullan, J.E. Hawkinson, E.M.F. de Velasco, B.S. Muntean, K.A. Martemyanov, R. Satterfield, S.M. Young, and S.A. Thayer. Automated live-cell imaging of synapses in rat and human neuronal cultures. Front. Cell. Neurosci. 13:1-14, 2019.

C.N. Paulson,K. John,R. Baxley,F. Kurniawan,R. Francis,B. Eichman,W. Chazin, H. Aihara, G.I. Georg, J.E. Hawkinson, and A.-K. Bielinsky. The anti-parasitic agent suramin and several of its analogs are inhibitors of the DNA binding protein Mcm10. Open Biology 9:190117, 2019.

A. Nakhi, C.M. McDermott, K.L. Stoltz, K. John,J.E. Hawkinson, E.A. Ambrose, A. Khoruts, M.J. Sadowsky, and P.I. Dosa. 7-Methylation of Chenodeoxycholic Acid Derivatives Yields a Substantial Increase in TGR5 Receptor Potency. J. Med. Chem. 62:6824-6830, 2019.

C.N. Paulson, X. Guan, W.C.K. Pomerantz, E. Schönbrunn, G.I. Georg, and J.E. Hawkinson. Design, Synthesis, and Characterization of a Novel Fluorescence Polarization Pan-BET Chemical Probe. ACS Med. Chem. Lett. 9:1223-1229, 2018.

L. Bhat, J. Hawkinson, M. Cantillon, D.G. Reddy, S.R. Bhat, C.E. Laurent, A. Bouchard, M. Biernat, and D. Salvail. Evaluation of the effects of RP5063, a novel, multimodal, serotonin receptor modulator, as single-agent therapy and co-administrated with sildenafil, bosentan, and treprostinil in a monocrotaline-induced pulmonary arterial hypertension rat model. Eur J Pharmacol. 827:159-166, 2018.

J.M. Pérez Ortiz, N. Mollema, N. Toker, C.J. Adamski, B. O’Callaghan, L. Duvick, J. Friedrich, M.A. Walters, J. Strasser, J.E. Hawkinson, H. Zoghbi, C. Henzler, H.T. Orr, and S. Lagalwar. Reduction of Protein Kinase A-mediated Phosphorylation of ATXN1-S776 in Purkinje Cells Delays Onset of Ataxia in a SCA1 Mouse Model. Neurobiol. Dis. 18: 30140-30142, 2018.

S.S. Syeda, G. Sánchez,K.H. Hong, J.E. Hawkinson, G.I. Georg, and G. Blanco. Design, synthesis, in vitro and in vivo evaluation of ouabain analogs as potent and selective Na,K-ATPase alpha-4 isoform inhibitors for male contraception. J. Med. Chem. 61:1800-1820, 2018.

X. Gu, V. Gupta, Y. Yang, J.-Y. Zhu,E.J. Carlson, C. Kingsley, J. Hawkinson, J.S. Tash, E. Schönbrunn,and G.I. Georg. Structure-Activity Studies of N-Butyl-1-deoxynojirimycin (NB-DNJ) Analogs: Discovery of Potent and Selective Aminocyclopentitol Inhibitors of GBA1 and GBA2. Chem. Med. Chem. 12, 1977– 1984, 2017.

J.E. Hawkinson, R. Sinville, D. Mudaliar, J. Shetty, T. Ward, J.C. Herr, and G.I. Georg.Potent Pyrimidine and Pyrrolopyrimidine Inhibitors of Testis-Specific Serine/Threonine Kinase 2 (TSSK2). Chem. Med. Chem. 12:1857-1865, 2017.

L. Bhat, J. Hawkinson, M. Cantillon, D.G. Reddy, S.R. Bhat, C.E. Laurent, A. Bouchard, M. Biernat, and D. Salvail. RP5063, a novel, multimodal, serotonin receptor modulator, prevents Sugen 5416-induced pulmonary arterial hypertension in rats. Eur. J. Pharm. 810:83-91, 2017.

L. Bhat, J. Hawkinson, M. Cantillon, D.G. Reddy, S.R. Bhat, C.E. Laurent, A. Bouchard, M. Biernat, and D. Salvail. RP5063, a novel, multimodal, serotonin receptor modulator, prevents monocrotaline-induced pulmonary arterial hypertension in rats. Eur. J. Pharm. 810:92-99, 2017.

J. Shetty, R. Sinville, I.A. Shumilin, W Minor, J. Zhang, J.E. Hawkinson, G.I. Georg, C.J. Flickinger, and J.C. Herr. Recombinant Production of Enzymatically Active Male Contraceptive Drug Target hTSSK2: Localization of the TSKS Domain Phosphorylated by TSSK2. Protein Expr. Purif. 121:88-96, 2016.

S.S. Syeda, E.J. Carlson, ­­M.R. Miller,R. Francis, D.E. Clapham, P.V. Lishko,J.E. Hawkinson,D. Hook, and G.I. Georg. The Fungal Sexual Pheromone Sirenin Activates the Human CatSper Channel Complex. ACS Chem. Biol. 11:452-9, 2016.