MRes/PhD Programme in Organic Chemistry: Drug Discovery

This 4-year programme offers students the opportunity to follow an integrated course of research and interdisciplinary study, in response to the needs of the pharmaceutical and biotechnology sectors for highly qualified postgraduate students as leaders in the discovery of new medicines.

Drug Discovery

The core of this programme provides outstanding training in synthetic organic chemistry applied to drug design. Students gain a breadth of experience in several areas of synthetic methodology before focusing on their main PhD research project. The first year of the course constitutes a formal MRes qualification and can be taken as a standalone course. In the first year students carry out two synthetic organic chemistry rotation projects and a biological rotation, as well as attending taught courses in synthetic chemistry, medicinal chemistry, pharmacology and molecular modelling.

There is a mixture of academic-led and industrially-led PhD research projects for students to choose from, with studentships supported by the EPSRC, the MRC, Novartis and by other  industrial sponsors. Each PhD research project has as the ultimate goal the delivery of successful early-phase drug discovery projects, in collaboration with leading biomedical research groups at UCL and at an industrial sponsor working at the cutting edge of biomedical research.


For many years UCL has had major research and teaching interests in drug discovery and medicinal chemistry. The first undergraduate degree programme in Medicinal Chemistry in the UK was started at UCL in 1974, following discussions between Professor James Black from the Department of Pharmacology and Professor Charles Vernon from the Department of Chemistry, and is still continuing today.

Since the solution of the human genome project there has been an exponential growth in the identification of new biological targets of potential importance to human disease, many of which offer opportunities for the development of small molecule therapeutics. It is increasingly recognised that leading universities can play an important role in carrying out the early-phase drug discovery process, as well as providing the next generation of research leaders in this field.

The School of Life and Medical Sciences (incorporating the Medical School) at UCL brings together one of the world's major concentrations of biomedical researchers, with ground breaking translational work underpinned by excellence in basic science, and a depth and breadth of biomedical research which is the strongest in the UK.

Programme Structure

The first year of the programme constitutes a formal MRes degree which can also be taken as a standalone qualification.  During the first 12 months, students take taught courses in drug design, advanced organic synthesis and molecular modelling, ensuring that they have a thorough foundation in these subjects.

In the first year, students also carry out two synthetic organic chemistry rotation projects, each lasting for five months. One of these rotation projects is linked to the final PhD project, and students have a free choice of the second rotation. Details of projects that have been offered to students in previous years are shown in the Project Titles tab.

At the end of the four months each student write a first year thesis describing their research on both synthetic organic chemistry rotation projects, and have a viva on this thesis.

Following successful completion of the MRes year (assessed via a thesis and viva), the student selects their final PhD project. Each student then carries out a short rotation in the laboratory of the collaborating biomedical research group at UCL or at an industrial sponsor, giving the student an interdisciplinary training in biomedical sciences.

In the second, third and fourth years each student continues research in their chosen PhD topic. The research is mainly based at UCL Chemistry, but also includes further placements at the industrial partner's laboratories where appropriate. 

Progress is monitored by a thesis committee, comprising chemistry and biomedical sciences supervisors and an independent advisor, which mentor the student throughout the programme. At the end of the second year the student presents a research report and a literature survey, and at the end of the third year the student presents a research report and a poster at the departmental poster day. These are assessed by the thesis committee. At the end of the fourth year the student gives a research seminar. 

Project Titles

List of projects offered to students in previous years:

Par1 Inhibition and Respiratory Disease - Steve Caddick

CASE Award with industrial sponsor

Acute lung injury is a major unmet medical need and there are very few methods for diagnosis and treatment. Many tissues within the body respond to various injurious insults by activating the coagulation cascade, a tightly regulated proteolytic system responsible for directing the formation of a fibrinous clot or plug at the site of injury as a key initial step in a repair process. In a number of disease states including chronic fibrotic lung diseases and acute lung injury, the balance of factors directed towards fibrin formation and deposition appears to be inappropriately skewed over time, even in the potential absence of the initiating insult, contributing significantly to debilitating and ultimately fatal lung damage. Proteinase-activated receptors (PARs; 1-4) are 7-transmembrane GPCRs with tethered ligands which are activated by cleavage of the extra-cellular receptor N-terminus by thrombin and other coagulation mediators. PAR1 is the high affinity thrombin receptor and activation by thrombin and another coagulation mediator factor Xa, results in the induction of multiple pro-fibrotic mediators promoting enhanced lung fibroblast proliferation, extracellular matrix production and myofibroblast differentiation. Pathogenic lung re-modelling caused by such processes has been experimentally reversed in experiments and has revealed this particular PAR receptor as a potential drug target for chronic fibrotic lung disease (such as idiopathic pulmonary fibrosis; IPF). The TRAP peptide, SFLLRN-NH2, of the natural tethered receptor ligand has provided a successful basis for discovery of small molecule PAR-1 antagonists for the treatment of cardiovascular disease. We propose to carry out a detailed SAR of these species directed toward the treatment of a variety of respiratory diseases. The synthetic work will focus initially on developing SAR on a known PAR-1 inhibitor.

Synthesis of Compounds with Enhanced Potential for the Oral Treatment of Asthma - Helen Hailes

CASE Award with industrial sponsor

Treatment of asthma is still carried out for the large part through steroids oral and inhaled. Oral steroids, although effective in treating asthma, have significant side effects, which mean that there is still a need to develop safer oral treatments. The project aims to design and synthesise novel orally bio-available small molecules with dual pharmacology to enable interaction with two validated pro-inflammatory biological cascades, yielding compounds with enhanced potential to treat asthma. The project will utilise novel synthetic methodology, medicinal chemistry and computational design to achieve the discovery of the target compounds. 

Design of novel selective histone deacetylase HDAC 11 inhibitors - Charles Marson

CASE Award with industrial sponsor

Histone deacetylases (HDACs) are the most important regulators of gene expression known to the emerging science of epigenetics. At least eighteen different types (isoforms) of mammalian HDACs have been described, one or morepertaining to almost every major category of disease known. Given the immense potential for novel therapies based on HDACs, it is unsurprising that HDAC inhibitors have received intense interest in recent years [1].

In this project, one particular isoform of HDAC is to be targeted, owing to its relevance to the biology of asthma and other chronic inflammatory diseases of the airway. Although there has been little or no drug development concerning this isoform, the clinical HDAC inhibitor MGCD0103, an anti-cancer agent, shows some inhibition for the relevant isoform.

In this project, starting from the structure of MGCD0103 we will design new compounds to probe and optimise isoform inhibition. That will be aided by molecular modeling of ligands into the active site of the HDAC.

This project offers training in synthetic organic and medicinal chemistry, developing agents against a novel target, and with excellent industrial support by GlaxoSmithKline.

[1] C. M. Marson, “Histone Deacetylase Inhibitors: Design, Structure-Activity Relationships and Therapeutic Implications for Cancer.”, Anti-Cancer Agents in Medicinal Chemistry 20099, 661-692. 

Synthesis of Biologically Active Oxetanes and Azetidines - Tom Sheppard

Four-membered rings are synthetically challenging targets with many potential uses in medicinal chemistry due to their rigid well-defined structure. However, their use is currently limited by the lack of available methods for the stereocontrolled synthesis of substituted derivatives. This is particularly true for highly substituted oxetanes and azetidines which are of considerable interest in a wide range of medicinal chemistry projects in the pharmaceutical industry, but are difficult to access using existing chemistry. In this project we are particularly interested in developing new synthetic routes to substituted azetidines. The introduction of an azetidine ring into a lead compound structure, in place of a piperidine ring for example, can often impart greater metabolic stability whilst maintaining high levels of activity. 

Development of tracers for imaging of excitatory neurotransmission with PET and SPECT - Erik Årstad

Over activation of excitatory neurotransmission can result in excessive accumulation of Ca2+ ions in neurons, leading to excitotoxicity and neuronal death. The resulting localised neuronal destruction is a central event in many acute and chronic brain disorders, including stroke, traumatic brain injury, Alzheimer's disease, Parkinson's disease, multiple sclerosis and epilepsy. Development of tracers for imaging of excitatory neurotransmission with positron emission tomography (PET) and single photon emission computed tomography (SPECT) may therefore enable early detection of neurodegenerative diseases, and would be of tremendous value for drug development. We propose to develop state-dependent ion channel radioligands for imaging of excitatory neurotransmission.

Anti-cancer therapeutics and a new pro-drug strategy - Jamie Baker

This project has two aims; 1) The design and synthesis of stabilised analogues of the peptide hormone somatostatin. Such analogues are widely sought for many clinical applications, including cancer treatment, due to the instability of somatostatin itselfin vivo. 2) The development of a new pro-drug strategy. Pro-drugs are extremely important in cutting-edge drug-development (such as magic-bullet therapy) as they prevent many undesired side effects and maximise efficacy.

Chemical screen for activators of epicardium-derived progenitor cells in cardiac repair and regeneration - Steve Caddick

We propose a phenotypic chemical screen using an in-house UCL Chemistry small molecule library for activators of a recently described population of adult epicardium-derived progenitor cells (EPDCs). EPDCs have the potential to contribute de novo blood vessels and cardiac muscle in the setting of ischaemic heart disease and myocardial infarction (“heart attack”). High throughput epicardial explants will be screened with small molecules against end points of cellular migration, proliferation and differentiation and further assessed for quantitative structure activity relationships. Affinity purification assays will be used to implicate candidate molecules with known functional biochemical signalling pathways in terms of EPDC phenotype and cell fate.

In silico design, chemical synthesis and crystallographic characterisation of TK inhibitors for targeted cell and tumor growth-rate suppression - Helen Hailes

The aim of the project is to design and synthesise a novel class of organism specific TK inhibitors that are not based on TPP analogues. A combination of computational ligand screening and high-throughput experimentation will be used to identify TK inhibitors for targeted cell and tumour growth-rate suppression. Analogues will be designed that are inherently straightforward to synthesise, and that are potent and specific inhibitors of only one TK homolog.

Small Molecule-Annexin probes: In silico Design, Synthesis, and Annexin Specificity - Helen Hailes

Annexins are Ca2+ and phospholipid binding proteins, expressed in both animals and plants, that are characterised by a highly α-helical and tightly packed protein core domain. The structures of many annexins have been elucidated and the biological function of several annexins is now understood. The challenge now is to identify small novel molecules for applications such as therapeutics, or as molecular probes with high affinity and specificity to individual annexins such as annexin 2, over other related proteins. By inhibiting the interactions between annexin 2 and its various ligands these would have potential uses in clinical (prostate) cancer treatments and as research tools to study annexin function in cell culture models.

Novel Antagonists of the Human Histamine H4 Receptor to counter Itch and Inflammatory Diseases - Charles Marson

The aim of this project is to synthesise, validate and patent a novel class of antagonists of the human histamine H4 receptor and to evaluate them as agents to diminish pruritus (itch).

Development of new small molecule probes and therapeutics targeting the allosteric binding site of the α7 nicotinic acetylcholine receptor, and its structural definition - Charles Marson

Our aim is to determine the pharmacophore pattern (the essential shape and charge distribution needed for a drug to bind to a receptor) corresponding to the α7 nicotinic acetylcholine receptors, and hence to develop effective, drug-like modulators of the α7 receptor that could ameliorate neurological and psychiatric disorders including Alzheimer's and schizophrenia.

Development of nitroimidazole MRI contrasting agents for the investigation of hypoxia - Michael J Porter

Despite the clinical importance of hypoxia and ischaemia, there arecurrently no effective methods for imaging hypoxic tissues in vivo. Thisproject aims to develop new hypoxia-selective MRI contrast agents bycoupling 2-nitroimidazole ? a motif which is known to bind to hypoxic cells? with contrast agents based on gadolinium(III) and stable organic freeradicals. The agent will be assessed and refined in collaboration withcolleagues in medical research: an effective agent would be adopted inmedical practice worldwide.

Identification of small molecule inhibitors of hFis1, a mitochondrial fission protein, as a novel therapeutic strategy for acute myocardial infarction - David Selwood (WIBR)

The overall aim of the project is to identify a small molecule inhibitor of the mitochondrial fission protein, hFis1. This inhibitor would be a prototype novel therapeutic agent for reducing myocardial ischaemia-reperfusion injury, which will benefit patients with coronary heart disease.

Synthesis of subtype selective ligands for nicotinic acetylcholine receptors - Tom Sheppard

Nicotinic acetylcholine receptors (nAChRs) are a subtype of cholinergic receptors of great importance for the effective function of the nervous system. There is considerable interest in the development of molecules (agonists, antagonists and allosteric modulators) that selectively target particular subtypes of neuronal nAChRs.1 Indeed, such compounds are currently in development as possible treatments for Alzheimer's disease, schizophrenia, Parkinson's disease and pain relief. In addition, the discovery of compounds that are selective for insect nAChRs has enabled the development of novel insecticides In this project we will synthesise a range of nAChR-selective ligands and investigate their mode of binding at a variety of receptor subtypes, with a view to developing a detailed understanding of how subtype selective ligands interact with the receptors, in order to successfully target nAChRs with important biological functions.

Development of selective inhibitors of Nav1.7 sodium channels - Alethea Tabor

Voltage-gated sodium channels (VGSCs) mediate fast neurotransmission and they are widely expressed in the central and peripheral nervous systems. Ideally, blockers specific for NaV1.7 (sensory neurons) or NaV1.4 (muscle) could selectively be used to treat pain and muscle disorders without causing adverse side effects. A lead compound for selective interaction with NaV1.7 channels is the tarantula venom peptide ProTx-II, an inhibitory cystine knot (ICK) structure which has been little explored. We propose to explore the requirements for selective NaV 1.7 blockers by synthesising and evaluating a number of ProTx-II analogues with one or more of the cystine bridges replaced by thioether bridges. The resulting selective blockers will then be modified for radiolabelled with fluorine-18 with the view to develop tracers for imaging with positron emission tomography (PET).

Development of Selective Inhibitors of Cathepsin D and Cathepsin E - Alethea Tabor

Antigen processing generally involves uptake of proteins into antigen presenting cells. These proteins are then cleaved into smaller fragments by a variety of protease enzymes to give small peptide fragments, which are then displayed on the cell surface and trigger the immune response. Understanding how this process works is crucial to developing new therapeutic approaches for autoimmune diseases. In this project we will develop a series of selective inhibitors of the aspartic protease cathepsin E, based on a newly isolated natural product, grassystatin C. We have previously shown that this enzyme has a non-redundant role in antigen processing. In contrast, the closely related proteinases cathepsin D plays an important role in regulated cell death (apoptosis) and hence in the resolution of inflammation. In order to interfere with cathepsin E activity for either experimental or therapeutic purposes, it is therefore essential to have inhibitors able to distinguish between these two enzymes.

Synthesis of Novel Peptidomimetics for the Treatment of Osteoporosis - Jon Wilden

Current treatment for rheumatoid arthritis and osteoporosis are in need of significant improvement, in particular, due to concerns arising from the major class of anti-osteoporotic drugs, the bisphosphonates. This project seeks to exploit a novel observation made in the Henderson laboratory, that a heat-shock protein (HSP60) isolated from the bacterium that causes tuberculosis is a very effective inhibitor of osteoclast formation (osteoclasts being one the bone cells responsible for naturally degrading bone and a cell implicated in the pathogenesis of osteoporosis and rheumatoid arthritis). Synthetic peptide and truncation mutagenesis studies have identified the sequence 460-491 as being responsible for the osteoclast inhibitory activity. This project will focus on the synthesis of short peptides and peptidomimetics that have been identified from HSP60 as being responsible for this protein's osteoclast inhibitory activity.

Design and Synthesis of Inhibitors of the chloride channel CLIC1 and inhibition of NADPH oxidase activity - Jon Wilden

Inappropriate activation of the enzyme NADPH oxidase has been implicated in numerous diseases including multiple sclerosis and Alzheimers's disease. Work in the Duchen lab has suggested that specific inhibition of a chloride channel (CLIC1) could be a viable therapeutic target for these diseases. Currently, only one inhibitor for this channel is known (IAA-94) but is insufficiently specific to be of therapeutic value. This project will focus on the generation of analogues of IAA-94 in order to identify new, specific and more potent inhibitors of CLIC1. At the end of the programme the student will be skilled in both organic synthesis and have hands-on experience of the biological assays used in the drug-discovery process.

How to Apply

Information on the application procedure is included below.


Applicants must be able to meet residence and qualification criteria. Full details are available on the EPSRC Guide to Studentship Eligibility.


Applicants should be settled in the UK, without being subject to any restriction on the period for which they may stay. Candidates who are British nationals and who have lived all their lives in the UK will automatically be eligible. Candidates who have been ordinarily resident in the UK for three years immediately prior to start date of this PhD programme should also be eligible.

Students who do not meet the eligibility criteria may still apply, however will need to apply for funding independently for example through UCL's Graduate School Scholarship.


Candidates who are applying for a fully-funded 4-year PhD place should have at least an MSci/MChem 2(i) degree or equivalent.

Candidates applying for the MRes programme should have at least a BSc 2(i) or equivalent.

Fees and Funding

Unfortunately, we currently have no funded places for this programme. If you are a student with a scholarship or are able to self-fund, please apply for the programme via the online application system, following the instructions in the 'how to apply tab'. Students who are interested in the general area of organic chemistry and drug discovery are encouraged to apply to UCL chemistry anyway as funded places occasionally arise at various points in the academic cycle.

Application Procedure

Unfortunately, we currently have no funded places for this programme. If you are a student with a scholarship or are able to self-fund, please apply for the programme via the online application system, following the instructions below. Students who are interested in the general area of organic chemistry and drug discovery are encouraged to apply to UCL chemistry anyway as funded places occasionally arise at various points in the academic cycle.

Online Application

Click here and select "Research Degree: Chemistry" from the list.
Under “Name(s) of Proposed Supervisors” please enter “PhD Programme in Drug Discovery”.

You will need to provide details of your referees as part of the online application. The system will contact your referees using these details. Please note: your application will not be processed until both your referees have submitted their references. You can use the on-line system to check whether your references have been submitted or to send your referees a reminder.

If you are unable to apply online for any reason please use the contact form under Further Information to contact the course organiser.

Deadline for Applications

The timeline for applications to the Drug Discovery MRes and PhD programme is shown below, please use the contact form under Further Information for exact dates and times.

  • Applications for 2014 entry are now open
  • Deadline for applications for 2014 entry: 5pm on Friday 28th February 2014 (For PhD applications).  Late August 2014 for MRes applications.
  • Interviews will be held shortly after the closing date.  Offers will be made as soon as possible after the interviews.

Further Information

Information on all aspects of studying at UCL as a postgraduate can be found here.

For any further information regarding the Drug Discovery PhD please contact the course organiser by completing the following form, outlining your request using the Additional Information box.

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