DERKSEN RESEARCH GROUP
OUR RESEARCH
Protein Degraders, Inhibitors and Modulators
In the Derksen lab, we aim to make biologically useful molecules using modern synthetic methods. We have a particular focus on targeting proteins involved in cancer and pain.
Representative examples of work that we have published so far in this area are:
1) Papatzimas, J. W.; Gorobets, E.; Maity, R.; Muniyat, M. I.; MacCallum, J. L.; Neri, P.; Bahlis, N. J.*; Derksen, D. J.* From Inhibition to Degradation: Targeting the Anti-Apoptotic Protein Myeloid Cell Leukemia 1 (MCL1) J. Med. Chem. 2019, 62, 11, 5522-5540.
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2) Papatzimas, J. W.; Gorobets, E.; Brownsey, D. K.; Maity, R.; Bahlis, N. J.; Derksen, D. J.* A General Strategy for the Preparation of Thalidomide-Conjugate Linkers SynLett 2017, 28, 2881-2885.
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3) LeGay, C. M.; Gorobets, E.; Iftinca, M.; Ramachandran, R.; Altier, C.; Derksen, D. J.* Natural-Product-Derived Transient Receptor Potential Melastatin 8 (TRPM8) Channel Modulators Org. Lett. 2016, 18, 2746-2749.
4) Harty, M.; Nagar, M.; Atkinson, L.; LeGay, C. M.; Derksen, D. J.* Bearne, S. L.* Inhibition of Serine and Proline Racemases by Substrate-Product Analogues Bioorg. Med. Chem. Lett. 2014, 24, 390-393.
doi: 10.1016/j.bmcl.2013.10.061
​​5) Kwok, C. H. T.; Harding, E. K.; Burma, N. E.; Markovic, T.; Massaly, N.; Van Den Hoogen, N. J.; Stokes-Heck, S.; Gambeta, E.; Komarek, K.; Yoon, H. J.; Navis, K. E.; McAllister, B. B.; Canet-Pons, J.; Fan, C.; Dalgarno, R.; Gorobets, E.; Papatzimas, J. W.; Zhang, Z.; Kohro, Y.; Anderson, C. L.; Thompson, R. J.; Derksen, D. J.; Morón, J. A.; Zamponi, G. W.; Trang, T. Pannexin-1 Channel Inhibition Alleviates Opioid Withdrawal in Rodents by Modulating Locus Coeruleus to Spinal Cord Circuitry. Nat. Commun. 2024, 15 (1), 6264. .
Strain Induced Reactivity
New methodology development in the Derksen group is based around the use of geometrically-strained compounds to induce novel reactivity in a stereo- and regio-chemically controlled manner. This work involves the use of light and metal-catalysis to promote reactions.
Representative examples of work that we have published so far in this area are:
1) Gorobets, E.; Wong, N. E.; Paton, R. S.; Derksen, D. J.* Divergent Photocyclization/1,4-Sigmatropic Rearrangements for the Synthesis of Sesquiterpenoid Derivatives Org. Lett. 2017, 19, 484-487.
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doi: 10.1021/acs.orglett.6b03635
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2) Brownsey, D. K.; Gorobets, E.; Derksen, D. J.* Beyond Geminal Diesters: Increasing the Scope of Metal-Mediated Vinylcyclopropane Annulations while Decreasing Pre-activation. Org. Biomol. Chem. 2018, 16, 3506-3523.
doi: 10.1039/C8OB00593A
3) Gorobets, E.; Parvez, M.; Derksen, D. J.; Keay, B. A.* Generation of Benzyne Species from Diphenylphosphoryl Derivatives - Simultaneous Exchange of Three Functional Groups Chem. Eur. J. 2016, 22, 8479-8482.
doi: 10.1002/chem.201601370
