Dr. David Uehling
Dr. David Uehling
Contact
Dr. David Uehling
Director, Medicinal Chemistry, Drug Discovery Program

david.uehling@oicr.on.ca

Director, Medicinal Chemistry, Drug Discovery Program

The focus of Dr. Uehling’s research is the design and synthesis of small molecules for cancer drug discovery.

Uehling has been involved in the development and application of inhibitors of understudied kinases and in the discovery of potent disruptors of protein protein intereactions of oncogenic targets. A related interest is the use of small molecules to exploit synthetic lethalities and molecularly defined tumour vulnerabilities in the validation of early-stage cancer targets. Uehling also has a long-standing interest in the discovery and use of chemical probe compounds and their use in phenotypic screening. He seeks to apply his experience from the pharmaceutical industry to work with academic scientists to explore and advance the translational potential of early-stage research opportunities to identify clinical drug candidate molecules.

Uehling obtained his undergraduate degree in Chemistry at UC San Diego. After obtaining a PhD in synthetic organic chemistry at the University of California, Berkeley, he was a post-doctoral fellow at Yale and Harvard Universities. For approximately 19 years, Uehling worked at GlaxoSmithKline (GSK) or its legacy companies in cardiovascular, diabetes and oncology research.  While working at GSK, he was a member of the project team that identified the topoisomerase I inhibitor lurtotecan for colorectal cancer and the beta-3 agonist solabegron for type 2 diabestes. In addition, he served as medicinal chemistry team leader in the discovery of of the B-Raf inhibitor dabrafenib (Tafinlar™), which is currently marketed for the treatment of patients with unresectable melanoma with a BRAF V600 mutation as well as BRAF V600-positive advanced or metastatic non small-cell lung cancer in combination with the MEK inhibitor trametinib (Mekinist™).

Experience & Education
  • Medicinal Chemist, GlaxoSmithKline (GSK)
  • Postdoctoral Fellow, Yale University
  • Postdoctoral Fellow, Harvard University
  • PhD, University of California Berkeley
Current Affiliations
  • Director, Medicinal Chemistry, Drug Discovery Program, OICR
Select Publications
  • Uehling, D. E.; Joseph, J.; Chung K-C.; Zhang, A. X.; Ler, S.; Prakesch, M. A.; Poda, G.; Grouleff, J.; Aman, A.; Kiyota, T.; Leung-Hagesteijn, C.; Konda, J. D.; Marcellus, R.; Griffin, C; Subramaniam, R.; Abibi, A; Strathdee, C. A.; Isaac, M. B.; Al-awar, R.; Tiedemann, R. E. Design, synthesis and characterization of 4-aminoquinazolines as potent inhibitors of the G protein-coupled receptor kinase 6 (GRK6) for the treatment of multiple myeloma. Journal of Medicinal Chemistry 2021, in press.
  • Pogmore, Justin P.; Uehling, David; and Andrews, David W. Pharmacological Targeting of Executioner Proteins: Controlling Life and Death. Journal of Medicinal Chemistry 2021, 64(9), 5276-5290.
  • Posternak, G.; Tang, X.; Maisonneuve, P.; Jin, T.; Lavoie, H.; Daou, S.; Orlicky, S.; Goullet de Rugy, T.; Caldwell, L.; Chan, K.; Aman A.; Prakesch, M.; Poda, G.; Mader, P.; Wong, C.; Maier, S.; Kitaygorodsky; J.; Larsen, B.; Colwill, K.; Yin, Z.; Ceccarelli, D. F.; Batey, R. A; Taipale, M.; Kurinov, I.; Uehling, D.; Wrana, J.; Durocher, D.; Gingras, A-C; Al-Awar, R.; Therrien, M.; and Sicheri, F.; Functional characterization of a PROTAC directed against BRAF mutant V600E. Nature Chemical Biology, 2020, 16 (11), 1170-1178
  • Uehling, David E.; Harris, Philip A. Recent progress on MAP kinase pathway inhibitors. Bioorganic & Medicinal Chemistry Letters, 2015, 25(19), 4047-4056.
  • Rheault, T. R.; Stellwagen, J. C.; Adjabeng, G. M.; Hornberger, K. R.; Petrov, K. G.; Waterson, A. G.; Dickerson, S. H.; Mook, R. A.; Laquerre, S. G.; King, A. J.; Rossanese, O. W.; Arnone, M. R.; Smitheman, K. N.; Kane-Carson, L. S.; Han, C.; Moorthy, G. S.; Moss, K. G.; Uehling, David E. Discovery of Dabrafenib: A Selective Inhibitor of Raf Kinases with Antitumor Actvity against B-Raf-Driven Tumors. ACS Medicinal Chemistry Letters 2013, 4(3), 358-362.
Research Areas
Disease Areas
Patents
  • Al-Awar, Rima; Isaac, Methvin; Chau, Anh My; Mamai, Ahmed; Watson, Iain; Poda, Gennady; Subramanian, Pandiaraju; Wilson, Brian; Uehling, David; Prakesch, Michael. Preparation of substituted pyrrolopyrimidinylacetamides as inhibitors of the BCL6 BTB domain protein-protein interaction and uses thereof. PCT Int. Appl. 2019, WO 2019153080.
  • Al-Awar, Rima; Isaac, Methvin; Chau, Anh My; Mamai, Ahmed; Watson, Iain; Poda, Gennady; Subramanian, Pandiaraju; Wilson, Brian; Uehling, David; Prakesch, Michael. Preparation of substituted pyrrolopyrimidinylacetamides as inhibitors of the BCL6 BTB domain protein-protein interaction and uses thereof. PCT Int. Appl. 2019, WO 2019153080.
  • Al-Awar, Rima; Isaac, Methvin; Chau, Anh My; Mamai, Ahmed; Watson, Iain; Poda, Gennady; Subramanian, Pandiaraju; Wilson, Brian; Uehling.  Preparation of tricyclic as inhibitors of interaction between the BCL6 BTB with its SMRT, NcoR and BCOR corepressors and/or as BCL6 degraders PCT Int. Appl. 2019, WO 2019119145.
  • Al-Awar, Rima; Isaac, Methvin; Joseph, Babu; Liu, Yong; Mamai, Ahmed; Poda, Gennady; Subramanian, Pandiaraju; Uehling, David; Wilson, Brian; Zepeda-Velazquez, Carlos Armando. Preparation of piperazinylaryl dihydropyridine carboxamides and related compounds as inhibitors of WDR5protein-protein binding useful in treatment of WDR5-mediated disorders. From PCT Int. Appl. 2019, WO 2019046944.
  • Al-Awar, Rima; Zepeda-Velazquez, Carlos Armando; Poda, Gennady; Isaac, Methvin; Uehling, David; Wilson, Brian; Joseph, Babu; Liu, Yong; Subramanian, Pandiaraju; Mamai, Ahmed.  N-Heterocyclylaryl arylamides and heteroarylamides as inhibitors of WDR5 protein-protein binding and their preparation.  PCT Int. Appl.  2017 WO 2017147701.
In the News
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