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.

doi: 10.1021/acs.jmedchem.9b00455

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.


doi: 10.1055/s-0036-1588539

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.

doi: 10.1021/acs.orglett.6b01222

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


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.

doi: 10.1021/acs.orglett.6b03635

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

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