Dr. Mark McLaughlin graduated with an MSci (Hons) degree in Chemistry in 2010 from Queen’s University Belfast, and continued in the same institution for his PhD. His PhD, carried out under the supervision of Prof. Matthew Cook focussed on the development of transition metal catalysed hydrometallation reactions and their subsequent use in synthesis. During his PhD, he was awarded a prestigious internship at Genentech, San Francisco, working with Dr James Crawford on the development of irreversible BTK inhibitors.
After being awarded his PhD in 2014, he moved to the Institute of Cancer Research, London as a CRUK postdoctoral training fellow under the supervision of Prof. Julian Blagg where he worked on the design and synthesis of selective chemical probes for JMJD2, a lysine demethylase enzyme implicated in various cancers.
In May 2016 he joined the group of Prof. Paul Brennan at the University of Oxford as a postdoctoral fellow focussing his research interests in fragment based approaches to small molecule inhibitors of several important biological targets.
In January 2018 he moved to Manchester Metropolitan University as a lecturer in medicinal chemistry where his group focusses on both medicinal and synthetic organic chemistry.
2010-2014 PhD "Highly Selective Hydrometallations and Their Application in Synthesis", Queen's University Belfast
Supervisor: Prof. Matthew Cook
2006-2010 MSci (Hons.) Chemistry, Queen's University Belfast
June 2016 - December 2017 Postdoctoral Fellow, Target Discovery Institute/Structural Genomics Consortium, University of Oxford
Supervisor: Prof. Paul Brennan
July 2014 - May 2016 Postdoctoral Training Fellow, Centre for Cancer Therapeutics, Insitute of Cancer Research
Supervisor: Prof. Julian Blagg
April 2012 - August 2012 Intern, Small Molecule Drug Discovery, Genentech, San Francisco, USA
Supervisor: Dr. James Crawford
Research in the The McLaughlin group is focussed on two areas; Synthetic Organic Chemistry and Medicinal Chemistry.
We are actively designing and synthesising small molecules to interact with a range of biological targets. Our group uses both structure based and fragment based drug discovery techniques to help in our designs. Below are several projects currently underway.
Targeting the Untargeted Kinome
It is well known that kinases have become one of the most important biological targets Image result for cyclin dependent kinasewithin drug discovery arena, with successes stemming from the initial FDA approval of Imatinib for chronic myeloid leukaemia. Although kinases have been extensively studied, the majority of research carried out on kinases only surveys a small percentage of the known kinome. This has resulted in a very skewed distribution of knowledge about their biological function. Our lab works to address this imbalance, and we have identified several important families to target. In particular we are focussing our efforts on cyclin-dependent kinases and pseudokinases, using small molecules to probe their biological function
Combating Rare Disease
It is an unfortunate fact that many global pharmaceutical companies are no longer developing drugs for rare disease. Our lab, in collaboration with both structural biologists and clinical biochemists, is working to benefit patients who are living with these often debilitating conditions. We use cutting edge screening platforms to identify chemical leads, which will be optimised for potency, selectivity and cellular activity. These small molecules will then be evaluated as a potential therapeutic by our network of collaborators. Our initial efforts are focussed on developing a substrate reduction therapy for a rare form of childhood epilepsy called pyridoxine dependent epilepsy or PDE.
Synthetic Organic Chemistry
The group is interested in developing new and useful synthetic transformations and using these to help us synthesise novel small molecules.
Alkaline earth metal catalysis
We are interested in using Group 2 metals as catalysts to power organic reactions, and in particular using calcium as a highly sustainable, redox neutral and environmentally benign metal catalyst.
Enantioselective Cross Coupling Reactions
The need to develop new methods to couple two, racemic partners together remain as important as ever. Our group aims to establish novel cross-coupling protocols to join traditionally inert coupling partners together in a stereoselective manner. Taking advantage of the numerous chiral ligands available, we aim to develop more robust and user friendly approaches to deliver stereoenriched compounds
Prof. Wyatt Yue, Structural Biology, Rare Diseases
Prof. Madalena Tarsounas, Molecular & Cell Biology, Oncology
Dr. Philippa Mills, Clinical Biochemistry, Metabolic Disorders
Prof. Paul Brennan, Medicinal Chemistry, Target Validation
AJ. Basson, MG. McLaughlin (2019). Functionalisation of Isoindolinones via a Calcium Catalysed Hosomi-Sakurai Allylation. Chemical Communications. 55, pp.8317-8317.
Y-V. Le Bihan, RM. Lanigan, B. Atrash, MG. McLaughlin, S. Velupillai, et al. (2019). C8-substituted pyrido[3,4-d]pyrimidin-4(3H)-ones: Studies towards the identification of potent, cell penetrant Jumonji C domain containing histone lysine demethylase 4 subfamily (KDM4) inhibitors, compound profiling in cell-based target engagement assays. European Journal of Medicinal Chemistry. 177, pp.316-337.
HJ. Kiely-Collins, I. Sechi, PE. Brennan, MG. McLaughlin (2018). Mild, calcium catalysed Beckmann rearrangements. Chem Commun (Camb). 54(6), pp.654-657.
V. Bavetsias, RM. Lanigan, GF. Ruda, B. Atrash, MG. McLaughlin, et al. (2016). 8-Substituted Pyrido[3,4-d]pyrimidin-4(3H)-one Derivatives As Potent, Cell Permeable, KDM4 (JMJD2) and KDM5 (JARID1) Histone Lysine Demethylase Inhibitors. Journal of medicinal chemistry. 59(4), pp.1388-1409.
MG. McLaughlin, CA. McAdam, MJ. Cook (2015). MIDA-vinylsilanes: selective cross-couplings and applications to the synthesis of functionalized stilbenes. Org Lett. 17(1), pp.10-13.
CA. McAdam, MG. McLaughlin, MJ. Cook (2015). An alkyne hydrosilylation–Hiyama coupling approach to highly functionalised 1,3-dienes. Organic Chemistry Frontiers. 2(5), pp.510-514.
MG. McLaughlin, MJ. Cook (2014). Highly diastereoselective hydrosilylations of allylic alcohols. Chem Commun (Camb). 50(26), pp.3501-3504.
AJS. Johnston, MG. McLaughlin, JP. Reid, MJ. Cook (2013). NaH mediated isomerisation-allylation reaction of 1,3-substituted propenols. Org Biomol Chem. 11(44), pp.7662-7666.
CA. McAdam, MG. McLaughlin, AJS. Johnston, J. Chen, MW. Walter, et al. (2013). Platinum catalysed hydrosilylation of propargylic alcohols. Org Biomol Chem. 11(27), pp.4488-4502.
MG. McLaughlin, MJ. Cook (2012). Domino alkene-isomerization-Claisen rearrangement strategy to substituted allylsilanes. J Org Chem. 77(4), pp.2058-2063.
JCA. Flanagan, LM. Dornan, MG. McLaughlin, NG. McCreanor, MJ. Cook, et al. (2012). The synthesis of N-heterocycles via copper/TEMPO catalysed aerobic oxidation of amino alcohols. Green Chemistry. 14(5), pp.1281-1281.
MG. McLaughlin, MJ. Cook (2011). PtCl2/XPhos: a highly efficient and readily available catalyst for the hydrosilylation of propargylic alcohols. Chem Commun (Camb). 47(39), pp.11104-11106.
A. Bye, N. Kriek, T. Sage, J. Mitchell, D. Donaghy, et al. Novel anti-platelet properties of dietary cucurbitacins. Jesus College, Cambridge, 12/9/2019.
October 2017 - Fragment to Lead Workshop, Bayer, Berlin, Germany
December 2015 - Researcher Mobility in Drug Discovery, Royal Society, UK
Journal of Organic Chemistry
New Journal of Chemistry
Visiting scientist, University of Oxford
Member of the Royal Society of Chemistry