Staff Profile

Mat joined Newcastle University in 2013 from Moffitt Cancer Center and oversees the activities of the protein science component of the Drug Discovery Unit. He has over 10 years experience at the interface between chemistry and cell biology using biophysical and biochemical techniques to aid characterisation of small molecule inhibitors of proteins and protein-protein complexes.  He has been involved in drug discovery projects targeting multiple classes of clinically relevant proteins encompassing a range of disease areas. Mat’s application of rational drug design has directly led to lead inhibitors that have advanced into cellular and animal studies, including RKI-1447, a potent inhibitor of ROCK1/ROCK2 and 09MA034 Aurora, a novel inhibitor of Aurora A. Mat also holds a position of leadership within Enabling Technologies as part of the Discovery of Medicines theme within the Faculty of Medical Sciences.

• Wood DJ, Korolchuk S, Tatum NJ, Wang L-Z, Endicott JA, Noble MEM, Martin MP. Differences in the conformational energy landscape of CDK1 and CDK2 suggest a mechanism for achieving selective CDK inhibition. Cell Chemical Biology 2019, 26(1), 121-130.e5.
• Myers SM, Miller DC, Molyneux L, Arasta M, Bawn RH, Blackburn TJ, Cook SJ, Edwards N, Endicott JA, Golding BT, Griffin RJ, Hammonds T, Hardcastle IR, Harnor SJ, Heptinstall AB, Lochhead PA, Martin MP, Martin NC, Newell DR, Owen PJ, Pang LC, Reuillon T, Rigoreau LJM, Thomas HD, Tucker JA, Wang L-Z, Wong A-C, Noble MEM, Wedge SR, Cano C. Identification of a novel orally bioavailable ERK5 inhibitor with selectivity over p38α and BRD4. European Journal of Medicinal Chemistry 2019, 178, 530-543.
• Wood D, Lopez-Fernandez JD, Knight LE, Al-Khawaldeh I, Gai C, Lin S, Martin MP, Miller DC, Cano C, Endicott JA, Hardcastle IR, Noble MEM, Waring MJ. FragLites - minimal, halogenated fragments displaying pharmacophore doublets. An efficient approach to druggability assessment and hit generation. Journal of Medicinal Chemistry 2019, 62(7), 3741-3752.
• Whittaker SR, Barlow C, Martin MP, Mancusi C, Wagner S, Self A, Barrie E, Te Poele R, Sharp S, Brown N, Wilson S, Jackson W, Fischer PM, Clarke PA, Walton MI, McDonald E, Blagg J, Noble M, Garrett MD, Workman P. Molecular profiling and combinatorial activity of CCT068127: a potent CDK2 and CDK9 inhibitor. Molecular Oncology 2018, 12(3), 287-304.
• Miller DC, Martin MP, Adhikari S, Brennan A, Endicott JA, Golding BT, Hardcastle IR, Heptinstall A, Hobson S, Jennings C, Molyneux L, Ng Y, Wedge SR, Noble MEM, Cano C. Identification of a novel ligand for the ATAD2 bromodomain with selectivity over BRD4 through a fragment growing approach. Organic and Biomolecular Chemistry 2018, 16(11), 1843-1850.
• Martin MP, Endicott JA, Noble MEM. Structure-based discovery of cyclin-dependent protein kinase inhibitors. Essays in Biochemistry 2017, 61(5), 439-452.
• Martin MP, Lawrence H, Lawrence NJ, Schonbrunn E, Sebti SM. Aurora Kinase Inhibitors and methods of making and using thereof. 9597329, 21/03/2017.
• Coxon C, Anscombe E, Harnor S, Martin M, Carbain B, Golding B, Hardcastle I, Harlow L, Korolchuk S, Matheson C, Newell D, Noble M, Sivaprakasam M, Tudhope SJ, Turner D, Wang L, Wedge SR, Wong C, Griffin R, Endicott J, Cano C. Cyclin-Dependent Kinase (CDK) Inhibitors; Structure-Activity Relationships and Insights into the CDK-2 Selectivity of 6-Substituted 2-Arylaminopurines. Journal of Medicinal Chemistry 2017, 60, 1746-1767.
• Zhu JY, Cuellar RAD, Berndt N, Lee HE, Olesen SH, Martin MP, Jensen JT, Georg GI, Schönbrunn E. Structural basis of Wee kinases functionality and inactivation by diverse small molecule inhibitors. Journal of Medicinal Chemistry 2017, 60(18), 7863-7875.
• Olesen SH, Zhu JY, Martin MP, Schonbrunn E. Discovery of Diverse Small-Molecule Inhibitors of Mammalian Sterile20-like Kinase 3 (MST3). ChemMedChem 2016, 11(11), 1137-1144.
• Brown NR, Korolchuk S, Martin MP, Stanley WA, Moukhametzianov R, Noble MEM, Endicott JA. CDK1 structures reveal conserved and unique features of the essential cell cycle CDK. Nature Communications 2015, 6, 6769.
• Anscombe E, Meschini E, Mora-Vidal R, Martin MP, Staunton D, Geitmann M, Danielson UH, Stanley WA, Wang LZ, Reuillon T, Golding BT, Cano C, Newell DR, Noble MEM, Wedge SR, Endicott JA, Griffin RJ. Identification and characterization of an irreversible inhibitor of CDK2. Chemistry & Biology 2015, 22(9), 1159-1164.
• Olesen SH, Ingles DJ, Zhu JY, Martin MP, Betzi S, Georg GI, Tash JS, Schönbrunn E. Stability of the human Hsp90-p50^Cdc37 chaperone complex against nucleotides and Hsp90 inhibitors, and the influence of phosphorylation by casein kinase 2. Molecules 2015, 20(1), 1643-1660.
• Massa BC, Martin MP, Noble ME, Endicott JA. Structural and functional characterization of Skp2-containing complexes. In: AACR 106th Annual Meeting 2015. 2015, Philadelphia, USA: American Association for Cancer Research.
• Ember SW, Zhu JY, Olesen SH, Martin MP, Becker A, Berndt N, Georg GI, Schönbrunn E. Acetyl-lysine binding site of bromodomain-containing protein 4 (BRD4) interacts with diverse kinase inhibitors. ACS Chemical Biology 2014, 9(5), 1160-1171.
• Martin M, Anscombe E, Meschini E, Staunton D, Geitmann M, Danielson UH, Wang LZ, Vidal RM, Reuillon T, Golding BT, Newell DR, Wedge S, Noble MEM, Endicott JA, Griffin RJ. Identification and characterization of an irreversible inhibitor of CDK2. In: 26th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics. 2014, Barcelona, Spain: Elsevier.
• Martin MP, Olesen SH, Georg GI, Schönbrunn E. Cyclin-dependent kinase inhibitor dinaciclib interacts with the acetyl-lysine recognition site of bromodomains. ACS Chemical Biology 2013.
• Schonbrunn E, Betzi S, Alam R, Martin MP, Becker A, Han H, Francis R, Chakrasali R, Jakkaraj S, Kazi A, Sebti SM, Cubitt CL, Gebhard AW, Hazlehurst LA, Tash JS, Georg GI. Development of highly potent and selective diaminothiazole inhibitors of cyclin-dependent kinases. Journal of Medicinal Chemistry 2013.
• Martin MP, Alam R, Betzi S, Ingles DJ, Zhu JY, Schönbrunn E. A novel approach to the discovery of small-molecule ligands of CDK2. Chembiochem 2012.
• Martin MP, Zhu JY, Lawrence HR, Pireddu R, Luo Y, Alam R, Ozcan S, Sebti SM, Lawrence NJ, Schönbrunn E. A novel mechanism by which small molecule inhibitors induce the DFG flip in Aurora A. ACS Chemical Biology 2012.
• Li R, Martin MP, Liu Y, Wang B, Patel RA, Zhu JY, Sun N, Pireddu R, Lawrence NJ, Li J, Haura EB, Sung SS, Guida WC, Schonbrunn E, Sebti SM. Fragment-based and structure-guided discovery and optimization of Rho kinase inhibitors. Journal of Medicinal Chemistry 2012.
• Pireddu R, Forinash KD, Sun NN, Martin MP, Sung SS, Alexander B, Zhu JY, Guida WC, Schönbrunn E, Sebti SM, Lawrence NJ. Pyridylthiazole-based ureas as inhibitors of Rho associated protein kinases (ROCK1 and 2). Medchemcomm 2012.
• Patel RA, Forinash KD, Pireddu R, Sun Y, Sun N, Martin MP, Schönbrunn E, Lawrence NJ, Sebti SM. RKI-1447 is a potent inhibitor of the Rho-associated ROCK kinases with anti-invasive and antitumor activities in breast cancer. Cancer Research 2012.
• Lawrence HR, Martin MP, Luo Y, Pireddu R, Yang H, Zhu JY, Ozcan S, Gervariya H, Sebti SM, Schönbrunn E, Lawrence NJ. The development of ortho-chlorophenyl substituted pyrimidines as exceptional potent Aurora A inhibitors. Journal of Medicinal Chemistry 2012.
• Betzi S, Alam R, Martin M, Lubbers DJ, Han H, Jakkaraj SR, Georg GI, Schönbrunn E. Discovery of a potential allosteric ligand binding site in CDK2. ACS Chemical Biology 2011.
• Marin-Rubio JL, Peltier-Heap RE, Duenas ME, Heunis T, Dannoura A, Inns J, Scott J, Simpson AJ, Blair HJ, Heidenreich O, Allan JM, Watt JE, Martin MP, Saxty B, Trost M. A Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Assay Identifies Nilotinib as an Inhibitor of Inflammation in Acute Myeloid Leukemia. Journal of Medicinal Chemistry 2022, 65(18), 12014-12030.
• Uguen M, Davison G, Sprenger LJ, Hunter JH, Martin MP, Turberville S, Watt JE, Golding BT, Noble MEM, Stewart HL, Waring MJ. Build–Couple–Transform: A paradigm for lead-like library synthesis with scaffold diversity. Journal of Medicinal Chemistry 2022, 65(16), 11322-11339.
• Miller DC, Reuillon T, Molyneux L, Blackburn T, Cook SJ, Edwards N, Endicott JA, Golding BT, Griffin RJ, Hardcastle I, Harnor SJ, Heptinstall A, Lochhead P, Martin MP, Martin NC, Myers S, Newell DR, Noble RA, Phillips N, Rigoreau L, Thomas H, Tucker JA, Wang L-Z, Waring MJ, Wong A-C, Wedge SR, Noble MEM, Cano C. Parallel Optimization of Potency and Pharmacokinetics Leading to the Discovery of a Pyrrole Carboxamide ERK5 Kinase Domain Inhibitor. Journal of Medicinal Chemistry 2022, 65(9), 6513-6540.
• Tucker JA, Martin MP. Recent advances in kinase drug discovery part i: The editors’ take. International Journal of Molecular Sciences 2021, 22(14), 7560.
• Douangamath A, Fearon D, Gehrtz P, Krojer T, Lukacik P, Owen CD, Resnick E, Strain-Damerell C, Aimon A, Abranyi-Balogh P, Brandao-Neto J, Carbery A, Davison G, Dias A, Downes TD, Dunnett L, Fairhead M, Firth JD, Jones SP, Keeley A, Keseru GM, Klein HF, Martin MP, Noble MEM, O'Brien P, Powell A, Reddi RN, Skyner R, Snee M, Waring MJ, Wild C, London N, von Delft F, Walsh MA. Crystallographic and electrophilic fragment screening of the SARS-CoV-2 main protease. Nature Communications 2020, 11(1), 5047.
• Martin MP, Noble MEM. Exiting the tunnel of uncertainty: crystal soak to validated hit. Acta Crystallographica. Section D, Structural Biology 2022, D78(11), 1294-1302.
• Davison G, Martin MP, Turberville S, Dormen S, Heath R, Heptinstall AB, Lawson M, Miller DC, Ng YM, Sanderson JN, Hope I, Wood DJ, Cano C, Endicott JA, Hardcastle IR, Noble MEM, Waring MJ. Mapping ligand interactions of bromodomains BRD4 and ATAD2 with FragLites and PepLites ─ Halogenated probes of druglike and peptide-like molecular interactions. Journal of Medicinal Chemistry 2022, 65(22), 15416-15432.