Expansion of MRCTs Drug Discovery Group (DDG)

Lead Research Organisation: MRC Technology MRCT

Abstract

Abstracts are not currently available in GtR for all funded research. This is normally because the abstract was not required at the time of proposal submission, but may be because it included sensitive information such as personal details.

Technical Summary

To expand and enhance MRCTs successful early stage drug discovery resource, in order to provide capacity to engage effectively with the MRC extramural programme in drug (and biological) development funded through the MRCs Developmental Pathway Funding Scheme (DPFS).

Publications

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Chapman TM (2015) Catechols and 3-hydroxypyridones as inhibitors of the DNA repair complex ERCC1-XPF. in Bioorganic & medicinal chemistry letters

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Chapman TM (2015) N-Hydroxyimides and hydroxypyrimidinones as inhibitors of the DNA repair complex ERCC1-XPF. in Bioorganic & medicinal chemistry letters

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Clark AJ (2016) ACTH Antagonists. in Frontiers in endocrinology

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Clark K (2011) Novel cross-talk within the IKK family controls innate immunity. in The Biochemical journal

 
Description Biomedical Catalyst
Amount £587,000 (GBP)
Organisation Innovate UK 
Sector Public
Country United Kingdom
Start 01/2013 
End 12/2016
 
Description DPFS
Amount £170,000 (GBP)
Organisation Medical Research Council (MRC) 
Sector Academic/University
Country United Kingdom
Start  
 
Description DPFS
Amount £525,000 (GBP)
Organisation Medical Research Council (MRC) 
Sector Academic/University
Country United Kingdom
Start 09/2010 
 
Description Michael J Fox Foundation
Amount £70,000 (GBP)
Organisation Michael J Fox Foundation 
Sector Charity/Non Profit
Country United States
Start 08/2011 
End 12/2011
 
Title Alphavbeta6 
Description Alphavbeta6 humanised antibody 
Type Of Material Antibody 
Year Produced 2011 
Provided To Others? Yes  
Impact Potential partnering event 
 
Title Biotinylated guanabenz 
Description Biotinylated guanabenz 
Type Of Material Technology assay or reagent 
Year Produced 2010 
Provided To Others? Yes  
Impact Used for target identification and association. Results pending 
 
Title CCR2 
Description Humanised antibody 
Type Of Material Antibody 
Provided To Others? No  
Impact Potential partnering event 
 
Title CDPK1 
Description Small molecule ligands 
Type Of Material Technology assay or reagent 
Provided To Others? No  
Impact Publications and further disection of pathway 
 
Title FPR2 agonist 
Description Two literature FPR2 agonists 
Type Of Material Technology assay or reagent 
Year Produced 2010 
Provided To Others? Yes  
Impact Target validation and disease association - ongoing 
 
Title Gpr35 antagonists 
Description Three literature Gpr35 antagonists 
Type Of Material Technology assay or reagent 
Year Produced 2010 
Provided To Others? Yes  
Impact Used for disease association, results pending. 
 
Title Migrastatin analogues 
Description Migrastatin analogues 
Type Of Material Technology assay or reagent 
Year Produced 2010 
Provided To Others? Yes  
Impact Target validation and disease association. Results pending 
 
Title MurC compounds 
Description Two literature MurC compounds 
Type Of Material Technology assay or reagent 
Year Produced 2011 
Provided To Others? Yes  
Impact Target validation and co-crystallisation studies - ongoing 
 
Title NK1 agonist 
Description Literature NK1 antagonist 
Type Of Material Technology assay or reagent 
Year Produced 2010 
Provided To Others? Yes  
Impact Material used for pathway validation. Results pending 
 
Title PKG compounds 
Description Two PfPKG inhibitors provided 
Type Of Material Technology assay or reagent 
Year Produced 2010 
Provided To Others? Yes  
Impact Target validation - ongoing 
 
Title PNKP Weinfeld compound 
Description PNKP inhibitor published by Weinfeld et al. 
Type Of Material Technology assay or reagent 
Year Produced 2010 
Provided To Others? Yes  
Impact Used to see if it was a good inhibitor of PNKP and for mechanistic studies. Our research identified it is not a very good inhibitor and is non-selective, hitting a wide range of kinases from the PPU panel. 
 
Title PROKR1 antagonists 
Description Six different PROKR1 antagonists were made from literature exaples 
Type Of Material Technology assay or reagent 
Year Produced 2010 
Provided To Others? Yes  
Impact Used for target validationa dn diseae association. Work is ongoing but initial results look to be linking PROKR1 to a specific disease of interest. 
 
Description ALK 
Organisation Georgetown University
Country United States 
Sector Academic/University 
PI Contribution Antibody humanisation
Collaborator Contribution Antibody generation
Impact Ongoing
Start Year 2012
 
Description APP/beta secretase 
Organisation Cardiff University
Country United Kingdom 
Sector Academic/University 
PI Contribution Antibody generation and humanisation
Collaborator Contribution Assays and reagents
Impact Ongoing
Start Year 2010
 
Description Anti-amyoid (AD) antibody humanisation 
Organisation Intellect Neurosciences, Inc.
Country United States 
Sector Private 
PI Contribution Humanisation and optimisation of antibodies
Impact Antibodies humanised succesfully
Start Year 2009
 
Description C5L2/Asp1 
Organisation University of Laval
Country Canada 
Sector Academic/University 
PI Contribution Antibody generation and humanisation
Collaborator Contribution Expertise and reagents
Impact Antibody humanisation
Start Year 2010
 
Description CCR2 
Organisation University of Regensburg
Country Germany 
Sector Academic/University 
PI Contribution Humanisation of antibodies
Collaborator Contribution Provision of mouse antibodies and assays
Impact Ongoing
Start Year 2010
 
Description CTLA4 
Organisation University of Aberdeen
Country United Kingdom 
Sector Academic/University 
PI Contribution Assay development
Collaborator Contribution Provision of reagents
Impact Robust assay
Start Year 2010
 
Description ERCC1 
Organisation University of Edinburgh
Country United Kingdom 
Sector Academic/University 
PI Contribution Screening and medicinal chemistry
Collaborator Contribution secondary assays and target validation
Impact Identification of hit molecules
Start Year 2012
 
Description EV71 
Organisation University of Hong Kong
Country Hong Kong 
Sector Academic/University 
PI Contribution Humanisation and optimisation of antibody
Collaborator Contribution In vitro and in vivo testing
Impact Antibody for partnering
Start Year 2015
 
Description FPR2 
Organisation Queen Mary University of London
Country United Kingdom 
Sector Academic/University 
PI Contribution Assay development and screening.
Collaborator Contribution Expertise and reagents
Impact Assays developed. Full drug discovery collaboration - biology, chemistry, pharmacology
Start Year 2010
 
Description Fascin 
Organisation Beatson Institute for Cancer Research
Country United Kingdom 
Sector Charity/Non Profit 
PI Contribution HTS screening versus target, hit validation and medicinal chemistry
Collaborator Contribution Fragment screening and supporting biology
Impact Ongoing
Start Year 2010
 
Description GPCR Deorphanisation 
Organisation DiscoveRx
Country United States 
Sector Private 
PI Contribution Screening and validation of hits versus 90 orphan GPCRS
Collaborator Contribution Provision of ligand library and screening capabilityProvision of cell lines for screening
Impact Deorphanised GPCR 88 and 35. GPRR88 subject of succesful MJFF grant.
Start Year 2009
 
Description GPCR Deorphanisation 
Organisation GlaxoSmithKline (GSK)
Country Global 
Sector Private 
PI Contribution Screening and validation of hits versus 90 orphan GPCRS
Collaborator Contribution Provision of ligand library and screening capabilityProvision of cell lines for screening
Impact Deorphanised GPCR 88 and 35. GPRR88 subject of succesful MJFF grant.
Start Year 2009
 
Description GalR2-ADC 
Organisation University of Bristol
Country United Kingdom 
Sector Academic/University 
PI Contribution Generation of GalR2 antibody drug conjugate
Collaborator Contribution Biology expertise
Impact Generation of novel GalR2 based ADC
Start Year 2013
 
Description IL-16 
Organisation Mount Sinai Hospital (USA)
Country United States 
Sector Hospitals 
PI Contribution Antibody humnisation
Collaborator Contribution antibody generation
Impact Publication and poster
Start Year 2012
 
Description IL17BR 
Organisation Medical Research Council (MRC)
Department MRC Laboratory of Molecular Biology (LMB)
Country United Kingdom 
Sector Public 
PI Contribution Humanisation and affinity maturation of a potent antibody
Collaborator Contribution Animal models and biology expertise
Impact Generation of a potent antibody plus supporting in vivo data for partnering
Start Year 2012
 
Description Integrin alpha v beta 6 
Organisation University College London
Country United Kingdom 
Sector Academic/University 
PI Contribution Antibody generation and humanisation
Collaborator Contribution Expertise and reagents
Impact Humanised antibody for partnering
Start Year 2010
 
Description MALT1 
Organisation University of Lausanne
Country Switzerland 
Sector Academic/University 
PI Contribution Assay development and screening
Collaborator Contribution Biology expertise
Impact Development of HTS assay
Start Year 2014
 
Description MC2 
Organisation Queen Mary University of London
Country United Kingdom 
Sector Academic/University 
PI Contribution Drug discovery expertise, assay development and screening
Collaborator Contribution Expertise and reagents
Impact Ongoing
Start Year 2010
 
Description MC3 
Organisation Queen Mary University of London
Country United Kingdom 
Sector Academic/University 
PI Contribution Assay development, screening and small molecule ligand ID
Collaborator Contribution Expertise and reagents
Impact ID of novel chemical series which were partnered with a major Pharma company
Start Year 2010
 
Description MCR2 
Organisation Queen Mary University of London
Country United Kingdom 
Sector Academic/University 
PI Contribution Assay development, screening and medicinal chemistry
Collaborator Contribution Biology expertise
Impact Identification of novel small molecule ligands
Start Year 2013
 
Description MNK1 
Organisation AstraZeneca
Country United Kingdom 
Sector Private 
PI Contribution Medicinal chemistry and primary screening
Collaborator Contribution Secondary assays and phrmacology
Impact Research collaboration
Start Year 2011
 
Description Mouse hybridomas 
Organisation BioArctic Neuroscience
Country Sweden 
Sector Private 
PI Contribution Raising and humanisation of mouse antibodies
Impact Antibodies raised and humanised
Start Year 2009
 
Description Nicastrin 
Organisation Imperial College London
Country United Kingdom 
Sector Academic/University 
PI Contribution Antibody humanisation
Collaborator Contribution Antibody generation
Impact Ongoing
Start Year 2012
 
Description Novel Anti-malarial agents 
Organisation London School of Hygiene and Tropical Medicine (LSHTM)
Country United Kingdom 
Sector Academic/University 
PI Contribution Assay development, screening and medicinal chemistry to support a drug discovery programme
Collaborator Contribution The collaborator is an expert in his field and has in depth knowledge of the target as well as secondary assays to support a drug discovery programme. Note that the £525,000 finacial contribution is from a succesful DPFS application. This will be offset against the £5m grant.
Impact Successful DPFS grant application. Multidisciplinary invoilving, biology, chemistry, pharmacology, ADME.
Start Year 2009
 
Description Novel anti-bacterial compounds 
Organisation University of Warwick
Country United Kingdom 
Sector Academic/University 
PI Contribution Assay development, screening and medicinal chemistry for a full drug discovery programme.
Collaborator Contribution Provision of protein production and crystallography. Expert knowledge of target - experts in the field. Secondary assays.
Impact DPFS application - invited to Full Application which has yet to be reviewed by the Panel. Multidisciplinary involving biology, chemistry, pharmacology and ADME
Start Year 2009
 
Description Novel anti-cancer agents 
Organisation University of Sussex
Country United Kingdom 
Sector Academic/University 
PI Contribution Provision of assay development, screening and chemistry resources to support a drug discovery programme
Collaborator Contribution Our collaborator has brought a wealth of expertise and relevant knowledge to the porogramme as well as direct experience of the target in question and he is an opinion leader in his field.
Impact This programme has directly produced a collaboration with AZ (see Screening Compounds collaboration). Screening is ongoing to identify plausible hits for drug discovery. Multidisciplinary invoilving, biology, chemistry, pharmacology, ADME.
Start Year 2010
 
Description PAICS 
Organisation Netherlands Cancer Institute (NKI)
Country Netherlands 
Sector Academic/University 
PI Contribution Screening and development of potent selective inhibitors
Collaborator Contribution In vitro and in vivo testing
Impact Small molecule inhibitors
Start Year 2014
 
Description PAICS 
Organisation Netherlands Cancer Institute (NKI)
Country Netherlands 
Sector Academic/University 
PI Contribution Screening and medicinal chemistry
Collaborator Contribution Secondary assays and target validation
Impact Hit structures for optimisation
Start Year 2012
 
Description PfCDPK1 
Organisation Medical Research Council (MRC)
Department MRC National Institute for Medical Research (NIMR)
Country United Kingdom 
Sector Public 
PI Contribution Discovery of new PfCDPK1
Collaborator Contribution Identification of novel CDPK1 inhibnitors
Impact Publications
Start Year 2011
 
Description PfPKG 
Organisation London School of Hygiene and Tropical Medicine (LSHTM)
Country United Kingdom 
Sector Academic/University 
PI Contribution DIscovery of novel small molecule inhibitors of PfPKG
Collaborator Contribution Provision of in vitro and in vivo testing
Impact Publications and patent
Start Year 2011
 
Description Screening Libraries 
Organisation AstraZeneca
Country United Kingdom 
Sector Private 
PI Contribution Provision of screens and reagents plus personnel to run screens and validate hits
Collaborator Contribution Provision of 100,000 compounds in screening ready plates for screening versus up to 10 biochemical targets, 5 selected by AZ and 5 by MRCT.
Impact To date three targets has been selected for screening by AZ. Multidisciplinary invoilving, biology, chemistry, pharmacology, ADME.
Start Year 2010
 
Description TPL2 
Organisation Medical Research Council (MRC)
Department MRC National Institute for Medical Research (NIMR)
Country United Kingdom 
Sector Public 
PI Contribution Assay development and screening
Collaborator Contribution Biology and reagents
Impact Development of a novel screen protocol
Start Year 2013
 
Description Transglutaminase 2 
Organisation University of Sheffield
Country United Kingdom 
Sector Academic/University 
PI Contribution Drug discovery, assay development, screening
Collaborator Contribution EXpertise and reagents
Impact We have partnered the project and a potential drug to a major Pharma company. The asset has just completed Ph I studies.
Start Year 2010
 
Description ULK 
Organisation University of Dundee
Country United Kingdom 
Sector Academic/University 
PI Contribution Screening and medicinal chemistry
Collaborator Contribution Secndary assays and target validation
Impact None yet
Start Year 2013
 
Description VCAM-1 
Organisation University of Oxford
Country United Kingdom 
Sector Academic/University 
PI Contribution Antibody generation
Collaborator Contribution Provision of expertise and assays
Impact Successful DPFS application
Start Year 2009
 
Description iC3b 
Organisation University College London
Country United Kingdom 
Sector Academic/University 
PI Contribution Drug discovery capapability and expertise.
Collaborator Contribution Expertise and reagents
Impact Ongoing
Start Year 2010
 
Title Humanized anti-CD20 antibodies 
Description Humanized anti-CD20 antibodies 
IP Reference WO2010080528 
Protection Patent application published
Year Protection Granted 2010
Licensed Commercial In Confidence
Impact New antibodies for treating disease
 
Title MC3 
Description Identification of novel small molecule ligands 
IP Reference  
Protection Protection not required
Year Protection Granted 2014
Licensed Commercial In Confidence
Impact Identification of novel small molecule ligands to support candidate seeking programme
 
Title Preparation of pyrazolopyridine compounds as kinase inhibitors. 
Description pyrazolopyridine compounds as kinase inhibitors 
IP Reference WO2010106333 
Protection Patent application published
Year Protection Granted 2010
Licensed Commercial In Confidence
Impact First known selective inhibitor of this kinase
 
Title Preparation of pyrimidine derivatives capable of inhibiting one or more kinases 
Description pyrimidine derivatives capable of inhibiting one or more kinases 
IP Reference WO2009122180 
Protection Patent application published
Year Protection Granted 2009
Licensed No
Impact Selective tool compounds for disease association studies
 
Title Preparation of pyrrolopyrimidines as kinase inhibitors 
Description pyrrolopyrimidines as kinase inhibitors 
IP Reference WO2010100431 
Protection Patent application published
Year Protection Granted 2010
Licensed No
Impact Highly selective inhibitors as tool compounds for disease association
 
Title TG2 
Description Identification of novel TG2 humanised antibody 
IP Reference  
Protection Protection not required
Year Protection Granted 2014
Licensed Commercial In Confidence
Impact Expansion of scientific knowledge and preclinical candidate licensed
 
Title MCR3 
Description Small molecule ligands 
Type Therapeutic Intervention - Drug
Current Stage Of Development Initial development
Year Development Stage Completed 2015
Development Status Under active development/distribution
Impact New tools made available 
 
Title TG2 
Description TG2 antibody for fibrosis 
Type Therapeutic Intervention - Drug
Current Stage Of Development Initial development
Year Development Stage Completed 2013
Development Status Under active development/distribution
Impact Novel approach to treating pulmonary fibrosis 
 
Title alphavbeta6 
Description alphavbeta6 humanised antibody 
Type Therapeutic Intervention - Drug
Current Stage Of Development Refinement. Non-clinical
Year Development Stage Completed 2011
Development Status Actively seeking support
Impact Potential new drug 
 
Description AstraZeneca 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Participants in your research and patient groups
Results and Impact Talk to senior executives.

Signing of compound screening agreement
Year(s) Of Engagement Activity 2009,2010
 
Description Crowd Sourcing Conference 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact Invited audience of 150 delegates

Requests for more information
Year(s) Of Engagement Activity 2011
 
Description Dementia consortium 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Media (as a channel to the public)
Results and Impact Interviews resulted in articles in the Guardian and Times newspapers

Sparked other press agencies contacting us for quotes and input.
Year(s) Of Engagement Activity 2014
 
Description ELRIG conference 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact Conference talk
Year(s) Of Engagement Activity 2015
 
Description Eisai Pharma 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact Talk to six senior executives fro Eisai

Desire by Eisai to work with MRCT on new targets
Year(s) Of Engagement Activity 2010
 
Description GSK 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Participants in your research and patient groups
Results and Impact Presentation on output from GPCR de-orphainsation programme

Interest from GSK in further collaborations and in-licencing
Year(s) Of Engagement Activity 2009,2010
 
Description Global Alliance on Drug Discovery 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Other academic audiences (collaborators, peers etc.)
Results and Impact Awareness of drug discovery respource for academics worldwide

Approaches by academics to access resource and work with Alliance
Year(s) Of Engagement Activity 2013
 
Description Miptech Conference 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact Over 200 people attended

Requests for more information
Year(s) Of Engagement Activity 2011
 
Description SBS conference 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact talk in front of several hundred pharma, biotech and academic scientists

More approaches to MRCT about collaborations
Year(s) Of Engagement Activity 2009,2010