![John Atack](https://profiles-cardiff.imgix.net/attachments/23?w=200&h=200&auto=format&crop=faces&fit=crop&q=90")
Professor John Atack
Director, Medicines Discovery Institute
School of Biosciences
- AtackJ@cardiff.ac.uk
- +44 29208 76983
- Main Building, Park Place, Cardiff, CF10 3AT
Overview
I am a molecular pharmacologist with over 25 years of drug discovery experience, primarily in the field of neuroscience. During this time, I have contributed to the earliest stages of drug discovery (target identification and target validation) all the way through to Phase 1 and Phase 2 clinical trials.
I have worked on a number of different types of drug targets (enzymes, G-protein-coupled receptors and ion channels) covering a range of neurodegenerative diseases (e.g. Alzheimer’s, Huntington’s and Parkinson’s diseases) and psychiatric disorders (bipolar disorder, schizophrenia, generalised anxiety disorder, depression). I am particularly interested in the translational aspects of preclinical drug discovery which give confidence that a particular drug candidate can engage with the target and produce a functional readout in man.
My favourite drug and mechanism of action? Well, that would have to be diazepam and the GABAA receptor ... Or maybe it is ketamine and the NMDA receptor … Or lithium and however that works in bipolar disorder … Not to mention donepezil, so I won’t.
Publication
2022
- An, H., Elvers, K. T., Gillespie, J. A., Jones, K., Atack, J. R., Grubisha, O. and Shelkovnikova, T. A. 2022. A toolkit for the identification of NEAT1_2/paraspeckle modulators. Nucleic Acids Research 50(20), article number: e119. (10.1093/nar/gkac771)
- Collins, R. et al. 2022. Comparative analysis of small-molecule limk1/2 inhibitors: chemical synthesis, biochemistry, and cellular activity. Journal of Medicinal Chemistry (10.1021/acs.jmedchem.2c00751)
- Noble, J. W. and Atack, J. R. 2022. Exploring Calbindin-IMPase fusion proteins structure and activity. Biochemistry and Biophysics Reports 30, article number: 101266. (10.1016/j.bbrep.2022.101266)
- Gendron, T. et al. 2022. Multi‐patient dose synthesis of [18F] Flumazenil via a copper‐mediated 18F‐fluorination. EJNMMI Radiopharmacy and Chemistry 7, article number: 5. (10.1186/s41181-022-00158-z)
2021
- Manzo, M. A. et al. 2021. Inhibition of a tonic inhibitory conductance in mouse hippocampal neurones by negative allosteric modulators of α5 subunit-containing γ-aminobutyric acid type A receptors: implications for treating cognitive deficits. British Journal of Anaesthesia 126(3), pp. 674-683. (10.1016/j.bja.2020.11.032)
2020
- Fenn, G., Waller-Evans, H., Atack, J. R. and Bax, B. D. 2020. Crystallization and structure of ebselen bound to cysteine 141 of human inositol monophosphatase (IMPase). Acta Crystallographica Section F: Structural Biology Communications F76(10), pp. 469-476. (10.1107/S2053230X20011310)
- Maramai, S., Benchekroun, M., Ward, S. E. and Atack, J. R. 2020. Subtype selective y-Aminobutyric acid type A receptor (GABAAR) modulators acting at the benzodiazepine binding site: An update. Journal of Medicinal Chemistry 63(7), pp. 3425-3446. (10.1021/acs.jmedchem.9b01312)
- Koulouris, C. R., Bax, B. D., Atack, J. R. and Roe, S. M. 2020. Conformational flexibility within the small domain of human serine racemase. Acta Crystallographica Section F: Structural Biology Communications 76(2), pp. 65-73. (10.1107/S2053230X20001193)
- Ward, S. E. et al. 2020. Pharmacological characterisation of MDI-222, a novel AMPA receptor positive allosteric modulator with an improved safety profile. Journal of Psychopharmacology 34(1), pp. 93-102. (10.1177/0269881119872198)
2019
- Raulin, A., Kraft, L., Al-Hilaly, Y. K., Xue, W., McGeehan, J. E., Atack, J. R. and Serpell, L. 2019. The molecular basis for apolipoprotein E4 as the major risk factor for late-onset Alzheimer's disease. Journal of Molecular Biology 431(12), pp. 2248-2265. (10.1016/j.jmb.2019.04.019)
- Kraft, L., Serpell, L. C. and Atack, J. R. 2019. A biophysical approach to the identification of novel ApoE chemical probes. Biomolecules 9(2), article number: 48. (10.3390/biom9020048)
2018
- Noble, J. W., Almalki, R., Roe, S. M., Wagner, A., Duman, R. and Atack, J. R. 2018. The X-ray structure of human calbindin-D28K: an improved model. Acta Crystallographica. Section D: Structural Biology 74(10), pp. 1008-1014. (10.1107/S2059798318011610)
- Duke, A. N. et al. 2018. Evidence that sedative effects of benzodiazepines involve unexpected GABAA receptor subtypes: Quantitative observation studies in rhesus monkeys. Journal of Pharmacology and Experimental Therapeutics 366(1), pp. 145-157. (10.1124/jpet.118.249250)
- Kraft, L., Roe, S. M., Gill, R. and Atack, J. R. 2018. Co-crystallization of human inositol monophosphatase with the lithium mimetic L-690,330. Acta Crystallographica. Section D: Structural Biology 74(10), pp. 973. (10.1107/S2059798318010380)
2017
- West, R. A. et al. 2017. African trypanosomiasis: Synthesis & SAR enabling novel drug discovery of ubiquinol mimics for trypanosome alternative oxidase. European Journal of Medicinal Chemistry 141, pp. 676-689. (10.1016/j.ejmech.2017.09.067)
- Khan, R. et al. 2017. Combining Sanford Arylations on Benzodiazepines with the nuisance effect. Advanced Synthesis & Catalysis 359(18), pp. 3261-3269. (10.1002/adsc.201700626)
2016
- Hornyak, P. et al. 2016. Mode of action of DNA-competitive small molecule inhibitors of tyrosyl DNA phosphodiesterase 2. Biochemical Journal 473(13), pp. 1869-1879. (10.1042/BCJ20160180)
- Gaekens, T. et al. 2016. Lipophilic nalmefene prodrugs to achieve a one-month sustained release. Journal of Controlled Release 232, pp. 196. (10.1016/j.jconrel.2016.04.029)
2015
- Spurny, R. et al. 2015. Molecular blueprint of allosteric binding sites in a homologue of the agonist-binding domain of the α7 nicotinic acetylcholine receptor. Proceedings of the National Academy of Sciences of the United States of America 112(19), article number: E2543. (10.1073/pnas.1418289112)
2014
- Atack, J. R. et al. 2014. JNJ-40255293, a novel adenosine A2A/A1 antagonist with efficacy in preclinical models of Parkinson's disease. ACS Chemical Neuroscience 5(10), pp. 1005-1019. (10.1021/cn5001606)
- Walker, S. et al. 2014. Development of an oligonucleotide-based fluorescence assay for the identification of tyrosyl-DNA phosphodiesterase 1 (TDP1) inhibitors. Analytical Biochemistry 454, pp. 17-22. (10.1016/j.ab.2014.03.004)
- Lavreysen, H. and Atack, J. 2014. Receptors: Functional assays. In: Stolerman, I. P. and Price, L. H. eds. Encyclopedia of Psychopharmacology. Berlin and Heidelberg: Springer, (10.1007/978-3-642-27772-6_208-2)
2013
- Lavreysen, H. et al. 2013. Pharmacological characterization of JNJ-40068782, a new potent, selective, and systemically active positive allosteric modulator of the mGlu2 receptor and its radioligand [3H]JNJ-40068782. Journal of Pharmacology and Experimental Therapeutics 346(3), pp. 514-527. (10.1124/jpet.113.204990)
- Shinday, N. M. et al. 2013. Reinforcing effects Of compounds lacking intrinsic efficacy at α1 subunit-containing GABAA receptor subtypes in midazolam- but not cocaine-experienced Rhesus Monkeys. Neuropsychopharmacology 38(6), pp. 1006-1014. (10.1038/npp.2012.265)
2012
- Langlois, X. et al. 2012. Pharmacology of JNJ-37822681, a specific and fast-dissociating D2 antagonist for the treatment of schizophrenia. Journal of Pharmacology and Experimental Therapeutics 342(1), pp. 91-105. (10.1124/jpet.111.190702)
- Mirza, N. R., Atack, J. and Wafford, K. 2012. Receptor subtypes: novel targets for novel medicines. Advances in Pharmacological Sciences 2012, article number: 529861. (10.1155/2012/529861)
2011
- Swanson, D. M. et al. 2011. The discovery and synthesis of JNJ 31020028, a small molecule antagonist of the Neuropeptide Y Y2 receptor. Bioorganic and Medicinal Chemistry Letters 21(18), pp. 5552-5556. (10.1016/j.bmcl.2011.06.136)
- Fischer, B. D., Atack, J. R., Platt, D. M., Reynolds, D. S., Dawson, G. R. and Rowlett, J. K. 2011. Contribution of GABAA receptors containing α3 subunits to the therapeutic-related and side effects of benzodiazepine-type drugs in monkeys. Psychopharmacology 215(2), pp. 311-319. (10.1007/s00213-010-2142-y)
- Atack, J. et al. 2011. MRK-409 (MK-0343), a GABAA receptor subtype-selective partial agonist, is a non-sedating anxiolytic in preclinical species but causes sedation in humans. Journal of Psychopharmacology 25(3), pp. 314-328. (10.1177/0269881109354927)
- Atack, J. et al. 2011. Preclinical and clinical pharmacology of TPA023B, a GABAA receptor α2/α3 subtype-selective partial agonist. Journal of Psychopharmacology 25(3), pp. 329-344. (10.1177/0269881109354928)
- Atack, J. 2011. GABAA receptor subtype-selective modulators. II. α5-selective inverse agonists for cognition enhancement. Current Topics in Medicinal Chemistry 11(9), pp. 1203-1214. (10.2174/156802611795371314)
- Atack, J. 2011. GABAA receptor subtype-selective modulators. I. α2/α3-selective agonists as non-sedating anxiolytics. Current Topics in Medicinal Chemistry 11(9), pp. 1176-1202. (10.2174/156802611795371350)
2010
- Eng, W. et al. 2010. Occupancy of human brain GABAA receptors by the novel α5 subtype-selective benzodiazepine site inverse agonist α5IA as measured using [11C]flumazenil PET imaging. Neuropharmacology 59(7-8), pp. 635-639. (10.1016/j.neuropharm.2010.07.024)
- Atack, J. R. 2010. Development of subtype-selective GABAA receptor compounds for the treatment of anxiety, sleep disorders and epilepsy. In: Monti, J. M., Pandi-Perumal, S. R. and Mohler, H. eds. GABA and Sleep. Basel: Springer, pp. 25-72., (10.1007/978-3-0346-0226-6_2)
- Letavic, M. A. et al. 2010. Pre-clinical characterization of aryloxypyridine amides as histamine H3 receptor antagonists: Identification of candidates for clinical development. Bioorganic and Medicinal Chemistry Letters 20(14), pp. 4210-4214. (10.1016/j.bmcl.2010.05.041)
- Stocking, E. M. et al. 2010. Novel substituted pyrrolidines are high affinity histamine H3 receptor antagonists. Bioorganic and Medicinal Chemistry Letters 20(9), pp. 2755-2760. (10.1016/j.bmcl.2010.03.071)
- Dixon, C. I. et al. 2010. Cocaine effects on mouse incentive-learning and human addiction are linked to α2 subunit-containing GABAA receptors. Proceedings of the National Academy of Sciences 107(5), pp. 2289-2294. (10.1073/pnas.0910117107)
- Licata, S. C. et al. 2010. Discriminative stimulus effects of L-838,417 (7-tert-butyl-3-(2,5-difluoro-phenyl)-6-(2-methyl-2H-[1,2,4]triazol-3-ylmethoxy)-[1,2,4]triazolo[4,3-b]pyridazine): Role of GABAA receptor subtypes. Neuropharmacology 58(2), pp. 357-364. (10.1016/j.neuropharm.2009.10.004)
- Shoblock, J. R. et al. 2010. In vitro and in vivo characterization of JNJ-31020028 (N-(4-{4-[2-(diethylamino)-2-oxo-1-phenylethyl]piperazin-1-yl}-3-fluorophenyl)-2-pyridin-3-ylbenzamide), a selective brain penetrant small molecule antagonist of the neuropeptide Y Y2 receptor. Psychopharmacology 208(2), pp. 265-277. (10.1007/s00213-009-1726-x)
- Atack, J. R. 2010. Preclinical and clinical pharmacology of the GABAA receptor α5 subtype-selective inverse agonist α5IA. Pharmacology and Therapeutics 125(1), pp. 11-26. (10.1016/j.pharmthera.2009.09.001)
- Ator, N. A., Atack, J. R., Hargreaves, R. J., Burns, H. D. and Dawson, G. R. 2010. Reducing abuse liability of GABAA/Benzodiazepine ligands via selective partial agonist efficacy at α1 and α2/3 subtypes. Journal of Pharmacology and Experimental Therapeutics 332(1), pp. 4-16. (10.1124/jpet.109.158303)
- Atack, J. R. et al. 2010. Benzodiazepine binding site occupancy by the Novel GABAA receptor subtype-selective drug 7-(1,1-Dimethylethyl)-6-(2-ethyl-2H-1,2,4-triazol-3-ylmethoxy)-3-(2-fluorophenyl)-1,2,4-triazolo[4,3-b]pyridazine (TPA023) in rats, primates, and humans. Journal of Pharmacology and Experimental Therapeutics 332(1), pp. 17-25. (10.1124/jpet.109.157909)
2009
- Atack, J. R. 2009. GABAA receptor α2/α3 subtype-selective modulators as potential nonsedating anxiolytics. Current Topics in Behavioral Neuroscience 2, pp. 331-360. (10.1007/7854_2009_30)
Adrannau llyfrau
- Lavreysen, H. and Atack, J. 2014. Receptors: Functional assays. In: Stolerman, I. P. and Price, L. H. eds. Encyclopedia of Psychopharmacology. Berlin and Heidelberg: Springer, (10.1007/978-3-642-27772-6_208-2)
- Atack, J. R. 2010. Development of subtype-selective GABAA receptor compounds for the treatment of anxiety, sleep disorders and epilepsy. In: Monti, J. M., Pandi-Perumal, S. R. and Mohler, H. eds. GABA and Sleep. Basel: Springer, pp. 25-72., (10.1007/978-3-0346-0226-6_2)
Erthyglau
- An, H., Elvers, K. T., Gillespie, J. A., Jones, K., Atack, J. R., Grubisha, O. and Shelkovnikova, T. A. 2022. A toolkit for the identification of NEAT1_2/paraspeckle modulators. Nucleic Acids Research 50(20), article number: e119. (10.1093/nar/gkac771)
- Collins, R. et al. 2022. Comparative analysis of small-molecule limk1/2 inhibitors: chemical synthesis, biochemistry, and cellular activity. Journal of Medicinal Chemistry (10.1021/acs.jmedchem.2c00751)
- Noble, J. W. and Atack, J. R. 2022. Exploring Calbindin-IMPase fusion proteins structure and activity. Biochemistry and Biophysics Reports 30, article number: 101266. (10.1016/j.bbrep.2022.101266)
- Gendron, T. et al. 2022. Multi‐patient dose synthesis of [18F] Flumazenil via a copper‐mediated 18F‐fluorination. EJNMMI Radiopharmacy and Chemistry 7, article number: 5. (10.1186/s41181-022-00158-z)
- Manzo, M. A. et al. 2021. Inhibition of a tonic inhibitory conductance in mouse hippocampal neurones by negative allosteric modulators of α5 subunit-containing γ-aminobutyric acid type A receptors: implications for treating cognitive deficits. British Journal of Anaesthesia 126(3), pp. 674-683. (10.1016/j.bja.2020.11.032)
- Fenn, G., Waller-Evans, H., Atack, J. R. and Bax, B. D. 2020. Crystallization and structure of ebselen bound to cysteine 141 of human inositol monophosphatase (IMPase). Acta Crystallographica Section F: Structural Biology Communications F76(10), pp. 469-476. (10.1107/S2053230X20011310)
- Maramai, S., Benchekroun, M., Ward, S. E. and Atack, J. R. 2020. Subtype selective y-Aminobutyric acid type A receptor (GABAAR) modulators acting at the benzodiazepine binding site: An update. Journal of Medicinal Chemistry 63(7), pp. 3425-3446. (10.1021/acs.jmedchem.9b01312)
- Koulouris, C. R., Bax, B. D., Atack, J. R. and Roe, S. M. 2020. Conformational flexibility within the small domain of human serine racemase. Acta Crystallographica Section F: Structural Biology Communications 76(2), pp. 65-73. (10.1107/S2053230X20001193)
- Ward, S. E. et al. 2020. Pharmacological characterisation of MDI-222, a novel AMPA receptor positive allosteric modulator with an improved safety profile. Journal of Psychopharmacology 34(1), pp. 93-102. (10.1177/0269881119872198)
- Raulin, A., Kraft, L., Al-Hilaly, Y. K., Xue, W., McGeehan, J. E., Atack, J. R. and Serpell, L. 2019. The molecular basis for apolipoprotein E4 as the major risk factor for late-onset Alzheimer's disease. Journal of Molecular Biology 431(12), pp. 2248-2265. (10.1016/j.jmb.2019.04.019)
- Kraft, L., Serpell, L. C. and Atack, J. R. 2019. A biophysical approach to the identification of novel ApoE chemical probes. Biomolecules 9(2), article number: 48. (10.3390/biom9020048)
- Noble, J. W., Almalki, R., Roe, S. M., Wagner, A., Duman, R. and Atack, J. R. 2018. The X-ray structure of human calbindin-D28K: an improved model. Acta Crystallographica. Section D: Structural Biology 74(10), pp. 1008-1014. (10.1107/S2059798318011610)
- Duke, A. N. et al. 2018. Evidence that sedative effects of benzodiazepines involve unexpected GABAA receptor subtypes: Quantitative observation studies in rhesus monkeys. Journal of Pharmacology and Experimental Therapeutics 366(1), pp. 145-157. (10.1124/jpet.118.249250)
- Kraft, L., Roe, S. M., Gill, R. and Atack, J. R. 2018. Co-crystallization of human inositol monophosphatase with the lithium mimetic L-690,330. Acta Crystallographica. Section D: Structural Biology 74(10), pp. 973. (10.1107/S2059798318010380)
- West, R. A. et al. 2017. African trypanosomiasis: Synthesis & SAR enabling novel drug discovery of ubiquinol mimics for trypanosome alternative oxidase. European Journal of Medicinal Chemistry 141, pp. 676-689. (10.1016/j.ejmech.2017.09.067)
- Khan, R. et al. 2017. Combining Sanford Arylations on Benzodiazepines with the nuisance effect. Advanced Synthesis & Catalysis 359(18), pp. 3261-3269. (10.1002/adsc.201700626)
- Hornyak, P. et al. 2016. Mode of action of DNA-competitive small molecule inhibitors of tyrosyl DNA phosphodiesterase 2. Biochemical Journal 473(13), pp. 1869-1879. (10.1042/BCJ20160180)
- Gaekens, T. et al. 2016. Lipophilic nalmefene prodrugs to achieve a one-month sustained release. Journal of Controlled Release 232, pp. 196. (10.1016/j.jconrel.2016.04.029)
- Spurny, R. et al. 2015. Molecular blueprint of allosteric binding sites in a homologue of the agonist-binding domain of the α7 nicotinic acetylcholine receptor. Proceedings of the National Academy of Sciences of the United States of America 112(19), article number: E2543. (10.1073/pnas.1418289112)
- Atack, J. R. et al. 2014. JNJ-40255293, a novel adenosine A2A/A1 antagonist with efficacy in preclinical models of Parkinson's disease. ACS Chemical Neuroscience 5(10), pp. 1005-1019. (10.1021/cn5001606)
- Walker, S. et al. 2014. Development of an oligonucleotide-based fluorescence assay for the identification of tyrosyl-DNA phosphodiesterase 1 (TDP1) inhibitors. Analytical Biochemistry 454, pp. 17-22. (10.1016/j.ab.2014.03.004)
- Lavreysen, H. et al. 2013. Pharmacological characterization of JNJ-40068782, a new potent, selective, and systemically active positive allosteric modulator of the mGlu2 receptor and its radioligand [3H]JNJ-40068782. Journal of Pharmacology and Experimental Therapeutics 346(3), pp. 514-527. (10.1124/jpet.113.204990)
- Shinday, N. M. et al. 2013. Reinforcing effects Of compounds lacking intrinsic efficacy at α1 subunit-containing GABAA receptor subtypes in midazolam- but not cocaine-experienced Rhesus Monkeys. Neuropsychopharmacology 38(6), pp. 1006-1014. (10.1038/npp.2012.265)
- Langlois, X. et al. 2012. Pharmacology of JNJ-37822681, a specific and fast-dissociating D2 antagonist for the treatment of schizophrenia. Journal of Pharmacology and Experimental Therapeutics 342(1), pp. 91-105. (10.1124/jpet.111.190702)
- Mirza, N. R., Atack, J. and Wafford, K. 2012. Receptor subtypes: novel targets for novel medicines. Advances in Pharmacological Sciences 2012, article number: 529861. (10.1155/2012/529861)
- Swanson, D. M. et al. 2011. The discovery and synthesis of JNJ 31020028, a small molecule antagonist of the Neuropeptide Y Y2 receptor. Bioorganic and Medicinal Chemistry Letters 21(18), pp. 5552-5556. (10.1016/j.bmcl.2011.06.136)
- Fischer, B. D., Atack, J. R., Platt, D. M., Reynolds, D. S., Dawson, G. R. and Rowlett, J. K. 2011. Contribution of GABAA receptors containing α3 subunits to the therapeutic-related and side effects of benzodiazepine-type drugs in monkeys. Psychopharmacology 215(2), pp. 311-319. (10.1007/s00213-010-2142-y)
- Atack, J. et al. 2011. MRK-409 (MK-0343), a GABAA receptor subtype-selective partial agonist, is a non-sedating anxiolytic in preclinical species but causes sedation in humans. Journal of Psychopharmacology 25(3), pp. 314-328. (10.1177/0269881109354927)
- Atack, J. et al. 2011. Preclinical and clinical pharmacology of TPA023B, a GABAA receptor α2/α3 subtype-selective partial agonist. Journal of Psychopharmacology 25(3), pp. 329-344. (10.1177/0269881109354928)
- Atack, J. 2011. GABAA receptor subtype-selective modulators. II. α5-selective inverse agonists for cognition enhancement. Current Topics in Medicinal Chemistry 11(9), pp. 1203-1214. (10.2174/156802611795371314)
- Atack, J. 2011. GABAA receptor subtype-selective modulators. I. α2/α3-selective agonists as non-sedating anxiolytics. Current Topics in Medicinal Chemistry 11(9), pp. 1176-1202. (10.2174/156802611795371350)
- Eng, W. et al. 2010. Occupancy of human brain GABAA receptors by the novel α5 subtype-selective benzodiazepine site inverse agonist α5IA as measured using [11C]flumazenil PET imaging. Neuropharmacology 59(7-8), pp. 635-639. (10.1016/j.neuropharm.2010.07.024)
- Letavic, M. A. et al. 2010. Pre-clinical characterization of aryloxypyridine amides as histamine H3 receptor antagonists: Identification of candidates for clinical development. Bioorganic and Medicinal Chemistry Letters 20(14), pp. 4210-4214. (10.1016/j.bmcl.2010.05.041)
- Stocking, E. M. et al. 2010. Novel substituted pyrrolidines are high affinity histamine H3 receptor antagonists. Bioorganic and Medicinal Chemistry Letters 20(9), pp. 2755-2760. (10.1016/j.bmcl.2010.03.071)
- Dixon, C. I. et al. 2010. Cocaine effects on mouse incentive-learning and human addiction are linked to α2 subunit-containing GABAA receptors. Proceedings of the National Academy of Sciences 107(5), pp. 2289-2294. (10.1073/pnas.0910117107)
- Licata, S. C. et al. 2010. Discriminative stimulus effects of L-838,417 (7-tert-butyl-3-(2,5-difluoro-phenyl)-6-(2-methyl-2H-[1,2,4]triazol-3-ylmethoxy)-[1,2,4]triazolo[4,3-b]pyridazine): Role of GABAA receptor subtypes. Neuropharmacology 58(2), pp. 357-364. (10.1016/j.neuropharm.2009.10.004)
- Shoblock, J. R. et al. 2010. In vitro and in vivo characterization of JNJ-31020028 (N-(4-{4-[2-(diethylamino)-2-oxo-1-phenylethyl]piperazin-1-yl}-3-fluorophenyl)-2-pyridin-3-ylbenzamide), a selective brain penetrant small molecule antagonist of the neuropeptide Y Y2 receptor. Psychopharmacology 208(2), pp. 265-277. (10.1007/s00213-009-1726-x)
- Atack, J. R. 2010. Preclinical and clinical pharmacology of the GABAA receptor α5 subtype-selective inverse agonist α5IA. Pharmacology and Therapeutics 125(1), pp. 11-26. (10.1016/j.pharmthera.2009.09.001)
- Ator, N. A., Atack, J. R., Hargreaves, R. J., Burns, H. D. and Dawson, G. R. 2010. Reducing abuse liability of GABAA/Benzodiazepine ligands via selective partial agonist efficacy at α1 and α2/3 subtypes. Journal of Pharmacology and Experimental Therapeutics 332(1), pp. 4-16. (10.1124/jpet.109.158303)
- Atack, J. R. et al. 2010. Benzodiazepine binding site occupancy by the Novel GABAA receptor subtype-selective drug 7-(1,1-Dimethylethyl)-6-(2-ethyl-2H-1,2,4-triazol-3-ylmethoxy)-3-(2-fluorophenyl)-1,2,4-triazolo[4,3-b]pyridazine (TPA023) in rats, primates, and humans. Journal of Pharmacology and Experimental Therapeutics 332(1), pp. 17-25. (10.1124/jpet.109.157909)
- Atack, J. R. 2009. GABAA receptor α2/α3 subtype-selective modulators as potential nonsedating anxiolytics. Current Topics in Behavioral Neuroscience 2, pp. 331-360. (10.1007/7854_2009_30)
Research
I am currently engaged in projects identifying molecules that interact with specific subtypes of the GABAA receptor or the AMPA subtype of glutamate receptor. These projects involve multidisciplinary teams of scientists using innovative medicinal chemistry (led by Prof. Simon Ward) and electrophysiology (Profs. Martin Gosling and Jerry Lambert and the University of Sussex and Dundee University, respectively) as well as a number of industrial collaborators (e.g., GSK and AstraZeneca).
I am also involved in a number of additional early-stage projects studying the mechanism of action of lithium and the role of ApoE4 in Alzheimer’s disease as well as novel approaches to modulating NMDA and kainate glutamate ion channel function.
I am driven by the desire to develop new treatments for the neurodegenerative and psychiatric disorders that have a profound impact on so many of our families and for which there remains a significant unmet medical need.
I am currently Principal Investigator on the following live grant awards:
- MICA - Valium without the sedation: Anxioselective GABAA receptor modulators for the treatment of anxiety disorders (Medical Research Council £3M)
- Alpha-GABAa receptor modulators for the treatment of cognitive impairment associated with Huntington's disease (Wellcome Trust £2M)
- Proof-of-Concept for a5-GABAAR PAMs in the treatment of psychosis (Wellcome Trust £500k)
- Developing small molecules as a neurosteroid replacement strategy for treating postpartum psychosis' (Wellcome Trust £500k)
- Allosteric modulators of extrasynaptic GABAA receptors for the treatment of postpartum depression (MRC – DPFS £650k)
- Inhibitors of serine racemase as novel therapeutic for treatment-resistant depression (Medical Research Council £18k)
- Spinout business plan for early stage drug discovery projects for Cardiff University Medicines Discovery Institute (iTPA £7.5k)
I am currently Co-Investigator on the following live grant awards:
- LIMK1 inhibitors - A novel, disease-modifying approach for the treatment of fragile X syndrome (Medical Research Council £2.5M)
- Transforming the treatment of schizophrenia: Design and development of AMPA receptor modulators with a much improved safety profile as novel drugs for treating the cognitive dysfunction associated with schizophrenia and other CNS disorders (Wellcome Trust £4M)
- Assay development and high-throughput screening for the identification of novel small molecules with a potential to reduce the NEAT1_2-mediated cytokine storm in COVID-19 (Welsh Government - Sêr Cymru – COVID 19 £75k)
- MSH3: a disease modifying approach to Huntington's disease (LoQus23 Therapeutics Ltd £500k)
- Transforming Cardiff Translation (Wellcome Trust £320k)
Biography
Following a PhD in neurochemical pathology in the Department of Pathology in Newcastle General Hospital, I worked for 5 years (1984-89) in the Laboratory of Neuroscience in the National Institute on Aging on the National Institutes of Health (NIH) campus in Bethesda, Maryland, studying pre- and post-mortem changes in the neurochemistry of patients with Alzheimer’s disease and Down syndrome.
During my time at the NIH, I started a project looking at developing inhibitors of acetylcholinesterase for the treatment of Alzheimer’s disease. From there, I joined the Merck Sharp and Dohme Neuroscience Research Centre in Harlow where I worked from 1989-2006 on a variety of in vitro and in vivo aspects of neuroscience drug discovery. When the site closed in as an indirect consequence of the Merck blockbuster drug Vioxx being taken off the market, I joined Janssen Pharmaceuticals, the pharmaceutical arm of Johnson & Johnson, where I worked from 2006 to 2012 (initially in La Jolla and then, attracted by the beer, chips and chocolate, in Beerse, Belgium).
I left the pharmaceutical industry to join the University of Sussex to help establish, with Prof. Simon Ward, the Sussex Drug Discovery Centre which, along with the addition of Prof. Martin Gosling gained a reputation for neuroscience drug discovery and ion channel pharmacology in particular.
In summer 2017, Simon and myself chose to move to Cardiff, attracted by the excellence of the disease mechanism and clinical science and the quality and collaborative spirit of the investigators with whom we will be interacting. However, we maintain our contacts with Martin who remains a key collaborator and allows us to expand our interest in ion channel pharmacology.
