Reader
- About
-
- Email Address
- i.greig@abdn.ac.uk
- Telephone Number
- +44 (0)1224 437370
- Office Address
IMS 6.35 Tel 01224 437370
- School/Department
- School of Medicine, Medical Sciences and Nutrition
Biography
I am a medicinal chemist involved in small molecule drug discovery, with an interest in developing and commercialising new treatments for a number of different diseases. I have developed novel treatments for a wide range of disorders including: heart failure, atherosclerosis, osteoporosis, neurodegeneration, and a project which is developing a first-in-class treatment for rheumatoid arthritis, which has recently met its Phase IIa clinical trial primary endpoint. Current projects include development of allosteric modulators of the cannabinoid receptors for the treatment of depression, schizophrenia/bipolar disorder, and liver fibrosis; and novel drugs for the prevention of neurodegeneration and treatment of multiple sclerosis.
My broader role within the Institute, as Head of Operations for the Kosterlitz Centre for Therapeutics, is to provide the expertise that allows us to identify the opportunities for target validation and drug discovery, to coordinate and fund the required multidisciplinary studies, and to manage the associated intellectual property and commercial aspects. Alongside medicinal chemistry and pharmacology, I have a background in physical organic chemistry at the University of St. Andrews and biophysics at Cornell University; I also am involved in the commercialisation process and was awarded an RSE Fellowship to provide the requisite experience, prior to founding two University of Aberdeen spin-out companies, OsteoRx (rheumatoid arthritis) and Signal Pharma (pain).
Following on from two UK-Canada Collaboration Development awards from the Foreign and Commonwealth Office, I am a regular Visiting Professor at the University of Toronto and have a number of joint research collaborations for drug discovery projects.
I am a keen mountaineer and have climbed various peaks in the Himalayas, Andes, Rockies and Cascades; high points have been the stunning Illimani in Bolivia (6439m) and Ojos Del Salado, the world's highest volcano, in Chile (6893m).
- Research
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Research Overview
Drug Discovery, Medicinal Chemistry, Intellectual Property Management, Commercialisation
Current Research
Novel small molecule drugs for the treatment of:
- Rheumatoid arthritis, psoriatic arthitis, psoriasis, inflammatory bowel disease
- Multiple sclerosis
- Schizophrenia and bipolar disorder
- Depression
- Non-alcoholic fatty liver disease and steatohepatitis
- Heart Failure
- Osteoporosis
- Cancer, expecially metastatic breast cancer
- Parkinson's disease and other neurodegenerative disorders
- Neuropathic and inflammatory pain
- Hypertension
- Obesity and other addictive disorders
Collaborations
The Kosterlitz Centre for Therapeutics has close links to the Toronto Centre for Collaborative Drug Research and I have a number of collaborative projects with the University of Toronto and affliated hospitals.
Funding and Grants
Motor Neurone Disease Association Development of RAR class ligands for treatment of motor neuron disease (2021–2025), £242k
Canadian Institutes for Health Research: Development and Characterization of Novel CB1 Allosteric Modulators (2020-2025), $765k
BBSRC PhD Studentship: Application of artificial intelligence-driven design of function-directed ligands for selective retinoic acid receptor binding (2018-2022), £93k
Roemex Ltd: Development of new drugs for the treatment of schizophrenia and bipolar disorder (2019–2021), $110k
Multiple Sclerosis Society: Identification and Characterization of Small Molecules for the Treatment of Multiple Sclerosis, (2017-2021) $838k
Canadian Institutes for Health Research, Proof of Principle Phase II : Development and Commercialisation of a Novel Treatment for Multiple Sclerosis, (2016-2018) $599k
Canadian Institutes for Health Research, Proof of Principle Phase I: Development and Validation of GPR55 Modulators for the Treatment Osteoclast-Mediated Disorders, (2016 - 2018), $155,600
BBSRC Follow-on Fund: Discovery that a dual-action screen (genomic/non-genomic) identifies retinoic acid receptor ligands of highest neurotrophic potency, (2017 - 2019), £249,710
Canadian Institutes for Health Research, Proof of Principle Phase II: Development and Commercialisation of Allosteric Modulators for the Treatment of Pain, (2015 - 2018), $489,920
Medical Research Council, Confidence in Concept: The Aberdeen Translational Accelerator Fund: bridging biomedical innovation and translational impact, (2015 – 2016), £200,000
Foreign and Commonwealth Office, UK-Canada Collaboration Development Awards, (2014 and 2015)
Signal Pharma Ltd: Development of a novel treatment for heart failure; (2013-2017), £151,274
Canadian Institutes for Health Research, Proof of Principle Phase I: Development and Testing of Small Molecule Allosteric Modulators for the Treatment of Pain, (2013–2014), $157,999
MSD SULSA Postdoctoral Fellowship: Development and Application of new fluorination techniques in the synthesis of therapeutics and diagnostics. (2013 – 2015)
MSD SULSA Postdoctoral Fellowship: Identification of compounds to interfere with chitin synthesis. (2013 – 2014)
MSD SULSA, PhD Studentship: A Novel Hypothalamic Receptor in Obesity and Metabolic Health, (2012-2015)
Tenovus, PhD Studentship: A Novel glutamate receptor. (2012 – 2015)
BBSRC: Development and Testing of Peripherally-restricted small molecule allosteric Inhibitors of the Cannabinoid CB1 Receptor, (2011 – 2012)
Development Trust: A novel therapy for diastolic heart failure, (2011 - 2013)
SULSA: Fragment-based Screening for Development of Inhibitors targeting a Vulnerable Epitope on HIV-1 Envelope Glycoprotein, (2012-2013)
SULSA Chemistry Catalyst Fund: Development of stable tumour-targeting peptide vectors; (2011)
SULSA Chemistry Catalyst Fund: Development of novel DDAH inhibitors for the treatment of neurodegenerative diseases; (2011)
SULSA Chemistry Catalyst Fund: Peripherally-restricted CB1 Allosteric Inhibitors for the Treatment of Type-2 Diabetes; (2011)
Development Trust: Commercial Validation of Kosterlitz Centre for Therapeutics Projects; Greig IR, Ross RA, Bewick G; Zanda M, Gow N (2011 - 2012)
Knowledge Transfer Grant: Screening of a Natural Product Library for Novel Chemotherapeutic Agents; (2010)
Parkinson's Disease Society: Assessment of a novel lead structure for the neuroprotective treatment of Parkinson's disease; (2010 - 2011)
Knowledge Transfer Grant: A Novel Retinoid Receptor with Therapeutic Potential; (2010)
BBSRC: Development and Testing of Small Molecule Allosteric Enhancers of the Cannabinoid CB1 Receptor; (2009 – 2010)
Knowledge Transfer Grant: Novel HTS platform for drug discovery in neurodegenerative disease; (2009)
NESTech (Scottish Universities Challenge Fund): Targeting novel receptors involved in metastatic breast cancer; (2009 - 2010)
SULSA: Discovery of lead small molecules targeting the allosteric binding site on the cannabinoid CB1 receptor; (2009)
Knowledge Transfer Grant: Allosteric modulators of the cannabinoid receptors for pain relief; (2008)
NESTech (Scottish Universities Challenge Fund): A Novel treatment for obesity; (2008 - 2009)
Modern Biosciences: Novel Anti-inflammatory agents; (2007 – 2010)
Knowledge Transfer Grant: A Neuroprotective therapy for Parkinson's disease; (2007)
Knowledge Transfer Grant: Commercialisation of Cannabinoid-based projects; (2006 – 2008)
NESTech (Scottish Universities Challenge Fund): Novel Bone Resorption Inhibitors; (2006 – 2008)
Arthritis Research Campaign: Small molecule inhibitors of TNF signalling as novel anti-rheumatic agents; (2005 – 2007)
Scottish Enterprise, Proof of Concept Follow on: Novel Bone Resorption Inhibitors; (2005 – 2006)
Royal Society of Edinburgh Enterprise Fellowship in Biotechnology: Novel therapeutic agents for bone disease; (2003 – 2004)
Scottish Enterprise, Proof of concept: Novel Bone Resorption Inhibitors: (2002 - 2004)
- Teaching
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Teaching Responsibilities
I am the coordinator for the undergraduate Biobusiness Programme
I am the course coordinator for
- BT2501 (Introduction to Biobusiness and Bioentrepreneurship
- SM3004 (Frontiers of Molecular Medicine and Therapeutics)
- BT3502 (Biobusiness)
- BT4506 (Advanced Biobusiness)
- BT5016 (Introduction to Commercialisation and Biobusiness
I contribute to the teaching and delivery of
- MC3504 (Molecular Microbiology)
- BT5013 (Small Molecule Drug Discovery)
- BT5015 (Introduction to Commercialisation and Biobusiness)
- BT5508 (Advanced Biobusiness and the Commercialisation of Bioscience)
- Publications
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Page 1 of 2 Results 1 to 50 of 62
Positive allosteric modulation of the cannabinoid CB1 receptor potentiates endocannabinoid signalling and changes ERK1/2 phosphorylation kinetics
British Journal of Pharmacology, vol. 181, no. 19, pp. 3642-3662Contributions to Journals: Articles- [ONLINE] DOI: https://doi.org/10.1111/bph.16433
- [ONLINE] View publication in Scopus
Inhibitors of PTP1B/NCK1 interaction and methods of making and using same
Patents: PatentsFluorinated perhexiline derivative attenuates vascular proliferation in pulmonary arterial hypertension smooth muscle cells
Vascular Pharmacology, vol. 156, 107399Contributions to Journals: ArticlesCB1 Receptor Negative Allosteric Modulators as a Potential Tool to Reverse Cannabinoid Toxicity
Molecules, vol. 29, no. 8, 1881Contributions to Journals: ArticlesAI is a viable alternative to high throughput screening: a 318-target study
Scientific Reports, vol. 14, no. 1, pp. 7526Contributions to Journals: Articles- [ONLINE] DOI: https://doi.org/10.1038/s41598-024-54655-z
- [OPEN ACCESS] http://aura.abdn.ac.uk/bitstream/2164/23165/1/AIMS_etal_SR_AI_Is_A_voR.pdf
- [ONLINE] View publication in Scopus
The atypical 'hippocampal' glutamate receptor coupled to phospholipase D that controls stretch-sensitivity in primary mechanosensory nerve endings is homomeric purely metabotropic GluK2
Experimental Physiology, vol. 109, no. 1, pp. 81-99Contributions to Journals: ArticlesSmall-molecule Targeting AMPA-mediated Excitotoxicity Has Therapeutic Effects in Mouse Models for Multiple Sclerosis
Science Advances, vol. 9, no. 49, eadj6187Contributions to Journals: ArticlesIn vitro characterisation of 6-methyl-3-(2-nitro-1-(thiophen- 2-yl)ethyl)-2-phenyl-1Hindole (ZCZ011) at the type 1 cannabinoid receptor: allosteric agonist or allosteric modulator?
ACS pharmacology & translational science, vol. 5, no. 12, pp. 1279–1291Contributions to Journals: Articles- [ONLINE] DOI: https://doi.org/10.1021/acsptsci.2c00160
Motor-like Tics are Mediated by CB2 Cannabinoid Receptor-dependent and Independent Mechanisms Associated with Age and Sex
Molecular Neurobiology, vol. 59, pp. 5070-5083Contributions to Journals: ArticlesAntidepressant Activity of Pharmacological and Genetic Deactivation of the Small-Conductance Calcium-Activated Potassium Channel Subtype-3
Psychopharmacology, vol. 239, no. 1, pp. 253-266Contributions to Journals: ArticlesA novel allosteric modulator of the cannabinoid CB1 receptor ameliorates hyperdopaminergia endophenotypes in rodent models
Neuropsychopharmacology, vol. 46, no. 2, pp. 413-422Contributions to Journals: ArticlesEvidence that cannabinoid CB1 receptors regulate intraocular pressure via two opposing mechanisms
Experimental Eye Research, vol. 200, 108241Contributions to Journals: Articles- [ONLINE] DOI: https://doi.org/10.1016/j.exer.2020.108241
- [ONLINE] View publication in Scopus
Genomic and non-genomic pathways are both crucial for peak induction of neurite outgrowth by retinoids
Cell Communication and Signaling, vol. 17, 40Contributions to Journals: Articles- [ONLINE] DOI: https://doi.org/10.1186/s12964-019-0352-4
- [OPEN ACCESS] http://aura.abdn.ac.uk/bitstream/2164/12240/1/Genomic_and_non_genomic_pathways.pdf
- [ONLINE] View publication in Scopus
- [ONLINE] View publication in Mendeley
Synthetic Retinoids for Use in RAR Mediated Conditions
Patents: PatentsThe Trifluoromethyl Group as a Bioisosteric Replacement of the Aliphatic Nitro Group in CB1 Receptor Positive Allosteric Modulators (PAMs)
Journal of Medicinal Chemistry, vol. 62, no. 10, pp. 5049-5062Contributions to Journals: Articles- [ONLINE] DOI: https://doi.org/10.1021/acs.jmedchem.9b00252
- [OPEN ACCESS] http://aura.abdn.ac.uk/bitstream/2164/14228/1/The_Trifluoromethyl_Group_Accepted_Manuscript.pdf
- [ONLINE] View publication in Mendeley
- [ONLINE] View publication in Scopus
- [ONLINE] https://abdn.pure.elsevier.com/en/en/researchoutput/the-trifluoromethyl-group-as-a-bioisosteric-replacement-of-the-aliphatic-nitro-group-in-cb1-receptor-positive-allosteric-modulators-pams(be1c59c4-139f-40c4-8183-31a797b12efb).html
Effects of glycol-split low molecular weight heparin on placental, endothelial, and anti-inflammatory pathways relevant to preeclampsia
Biology of Reproduction, vol. 99, no. 5, pp. 1082-1090Contributions to Journals: ArticlesSmall Molecule Inhibitors of Metabolic Enzymes Repurposed as a New Class of Anthelmintics
ACS Infectious Diseases, vol. 4, no. 7, pp. 1130–1145Contributions to Journals: ArticlesEnantiomer-specific positive allosteric modulation of CB1 signaling in autaptic hippocampal neurons
Pharmacological Research, vol. 129, pp. 475-481Contributions to Journals: Articles- [ONLINE] DOI: https://doi.org/10.1016/j.phrs.2017.11.019
- [OPEN ACCESS] http://aura.abdn.ac.uk/bitstream/2164/11473/1/Mitjavila_et_al_2017.pdf
Synthetic retinoids for use in RAR mediated conditions
Patents: PatentsDevelopment of Fluorinated Analogues of Perhexiline with Improved Pharmacokinetic Properties and Retained Efficacy
Journal of Medicinal Chemistry, vol. 60, no. 7, pp. 2780-2789Contributions to Journals: ArticlesDevelopment of indole sulfonamides as cannabinoid receptor negative allosteric modulators
Bioorganic & Medicinal Chemistry Letters, vol. 26, no. 18, pp. 4403-4407Contributions to Journals: ArticlesN-(4-HYDROXY-4-METHYL-CYCLOHEXYL)-4-PHENYL-BENZENESULFONAMIDE AND N-(4-HYDROXY-4-METHYL-CYCLOHEXYL)-4-(2-PYRIDYL)-BENZENESULFONAMIDE COMPOUNDS AND THEIR THERAPEUTIC USE
Patents: PatentsAsymmetric Synthesis and Absolute Configuration of (+)- and (–)-Perhexiline
Synthesis, vol. 48, no. 01, pp. 73-78Contributions to Journals: ArticlesA Cannabinoid CB 1 Receptor-Positive Allosteric Modulator Reduces Neuropathic Pain in the Mouse with No Psychoactive Effects
Neuropsychopharmacology, vol. 40, pp. 2948-2959Contributions to Journals: Articles- [ONLINE] DOI: https://doi.org/10.1038/npp.2015.148
- [OPEN ACCESS] http://aura.abdn.ac.uk/bitstream/2164/6041/2/Revision_May_15.pdf
- [ONLINE] View publication in Scopus
- [ONLINE] Springer Sharedit link
HPLC-MS-MS Determination of ZCZ-011, A Novel Pharmacological Tool for Investigation of the Cannabinoid Receptor in Mouse Brain Using Clean Screen FASt™ Column Extraction
Journal of analytical toxicology, vol. 39, no. 5, pp. 353-359Contributions to Journals: Articles- [ONLINE] DOI: https://doi.org/10.1093/jat/bkv015
Tyrphostin AG126 exerts neuroprotection in CNS inflammation by a dual mechanism
Glia, vol. 63, no. 6, pp. 1083-1099Contributions to Journals: ArticlesModulation of food consumption and sleep-wake cycle in mice by the neutral CB1 antagonist ABD459
Behavioural Pharmacology, vol. 26, no. 3, pp. 289-303Contributions to Journals: Articles- [ONLINE] DOI: https://doi.org/10.1097/FBP.0000000000000108
Identification of small molecule inhibitors of RANKL and TNF signalling as anti-inflammatory and antiresorptive agents in mice
Annals of the Rheumatic Diseases, vol. 74, no. 1, pp. 220-226Contributions to Journals: Articles- [ONLINE] DOI: https://doi.org/10.1136/annrheumdis-2013-203700
Fluoro-perhexiline compounds and their therapeutic use
Patents: PatentsIn-vivo pharmacological evaluation of the CB1-receptor allosteric modulator Org-27569
Behavioural Pharmacology, vol. 25, no. 2, pp. 182-185Contributions to Journals: Articles- [ONLINE] DOI: https://doi.org/10.1097/FBP.0000000000000027
N-(4-Hydroxy-4-methyl-cyclohexyl)-4-phenyl-benzenesulfonamides and N-(4-Hydroxy-4-methyl-cyclohexyl)-4-(2-pyridyl)-benzene sulfonamides and their therapeutic use
Patents: PatentsAryl-Phenyl-Sulfonamido-Cycloalkyl Compounds and Their Use
Patents: PatentsSynthesis and structure–activity relationship studies of novel tubulysin U analogues – effect on cytotoxicity of structural variations in the tubuvaline fragment
Organic & Biomolecular Chemistry, vol. 11, no. 14, pp. 2273-2287Contributions to Journals: Articles- [ONLINE] DOI: https://doi.org/10.1039/C3OB27111K
18f-labelled barbiturate compounds for use as positron emission imaging agents
Patents: PatentsDevelopment of triarylsulfonamides as novel anti-inflammatory agents
Bioorganic & Medicinal Chemistry Letters, vol. 23, no. 3, pp. 816-820Contributions to Journals: Articles- [ONLINE] DOI: https://doi.org/10.1016/j.bmcl.2012.11.067
Modulation of L-α-lysophosphatidylinositol/GPR55 mitogen-activated protein kinase (MAPK) signaling by cannabinoids
The Journal of Biological Chemistry, vol. 287, no. 1, pp. 91-104Contributions to Journals: Articles- [ONLINE] DOI: https://doi.org/10.1074/jbc.M111.296020
N-(ARYLALKYL)-1H-INDOLE-2-SULFONIC ACID AMIDE COMPOUNDS AND THEIR THERAPEUTIC USE AS CANNABINOID ALLOSTERIC MODULATORS
Patents: PatentsThe biphenyl-carboxylate derivative ABD328 is a novel orally active antiresorptive agent
Calcified Tissue International, vol. 87, no. 6, pp. 525-532Contributions to Journals: Articles- [ONLINE] DOI: https://doi.org/10.1007/s00223-010-9417-5
Discovery of biphenylketones as dual modulators of inflammation and bone loss
Bioorganic & Medicinal Chemistry Letters, vol. 20, no. 18, pp. 5548-5551Contributions to Journals: Articles- [ONLINE] DOI: https://doi.org/10.1016/j.bmcl.2010.07.055
Aryl-phenyl-sulfonamide-cycloalkyl compounds and their use
Patents: PatentsAryl-phenyl-sulfonamide-phenylene compounds and their use
Patents: Patents1,5-Diaryl-pyrazoles and their use as cannabinoid receptor neutral antagonists
Patents: PatentsNeuroprotective 3-phenylacrylonitrile (3-PAN) derivatives
Patents: PatentsIdentification of novel biphenyl carboxylic acid derivatives as novel antiresorptive agents that do not impair parathyroid hormone-induced bone formation
Endocrinology, vol. 150, no. 1, pp. 5-13Contributions to Journals: Articles- [ONLINE] DOI: https://doi.org/10.1210/en.2008-0998
Ketones and reduced ketones as therapeutic agents for the treatment of bone conditions
Patents: PatentsKetones and reduced ketones as therapeutic agents for the treatment of bone conditions
Patents: Patents2',4'-Dichloro-biphenyl-4-yl-hydroxyketones and related compounds and their use as therapeutic agents
Patents: Patents1,5-diaryl-pyrazoles as cannabinoid receptor neutral antagonists useful as therapeutic agents
Patents: PatentsABD56 causes osteoclast apoptosis by inhibiting the NFkappaB and ERK pathways
Biochemical and Biophysical Research Communications, vol. 371, no. 1, pp. 94-98Contributions to Journals: Articles- [ONLINE] DOI: https://doi.org/10.1016/j.bbrc.2010.04.007
Aminobisphosphonates Cause Osteoblast Apoptosis and Inhibit Bone Nodule Formation In Vitro
Calcified Tissue International, vol. 82, no. 3, pp. 191-201Contributions to Journals: Articles- [ONLINE] DOI: https://doi.org/10.1007/s00223-008-9104-y