Yr Athro John Atack
Cyfarwyddwr, y Sefydliad Darganfod Meddyginiaethau
Ysgol y Biowyddorau
- AtackJ@caerdydd.ac.uk
- +44 29208 76983
- Y Prif Adeilad, Plas y Parc, Caerdydd, CF10 3AT
Trosolwyg
Rwy'n ffarmacolegydd molecwlaidd gyda dros 25 mlynedd o brofiad o ddarganfod cyffuriau, ym maes y niwrowyddorau yn bennaf. Yn ystod y cyfnod hwn rydw i wedi cyfrannu at gamau cyntaf y broses darganfod cyffuriau (nodi targed a dilysu'r targed) ac wedi parhau i gyfrannu hyd at dreialon clinigol Cam 1 a Cham 2.
Rydw i wedi gweithio ar nifer o wahanol fathau o dargedau cyffuriau (ensymau, derbynyddion sydd wedi eu cyplu â phroteinau G, a sianeli ïonig) sy'n cwmpasu amrywiaeth o glefydau niwro-ddirywiol (e.e. clefydau Alzheimer, Huntington a Parkinson) ac anhwylderau seiciatrig (anhwylder deubegynol, sgitsoffrenia, anhwylder gorbryder cyffredinol, iselder). Mae gen i ddiddordeb penodol yn elfennau cyn-clinigol y broses darganfod cyffuriau, sy'n rhoi hyder bod cyffur posibl yn gallu cysylltu â'r targed a chynhyrchu allbwn gweithredol mewn bod dynol.
Beth yw fy hoff gyffur a mecanwaith gweithredu? Byddai'n rhaid i mi ddweud diasepam a'r derbynnydd GABAA ... Neu efallai cetamin a'r derbynnydd NMDA ... Neu lithiwm a sut bynnag mae hwnnw'n gweithio mewn anhwylder deubegynol ... Heb sôn am ddonepesil, felly wna' i ddim.
Cyhoeddiad
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)
Articles
- 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)
Book sections
- 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)
Ymchwil
Ar hyn o bryd rwy'n cymryd rhan mewn prosiectau sy'n adnabod moleciwlau sy'n rhyngweithio ag is-deipiau'r derbynnydd GABBA neu is-deip AMPA y derbynnydd glwtamad. Mae'r prosiectau'n cynnwys timau amlddisgyblaethol o wyddonwyr sy'n defnyddio cemeg feddygol arloesol (dan arweiniad yr Athro Simon Ward) ac electroffisioleg (yr Athro Martin Gosling o Brifysgol Sussex a'r Athro Jerry Lambert o Brifysgol Dundee) ynghyd â nifer o bartneriaid ym myd diwydiant (e.e. GSK ac AstraZeneca).
Rydw i hefyd yn cymryd rhan mewn nifer o brosiectau yn eu cyfnodau cynnar sy'n astudio mecanwaith gweithredu lithiwm a rôl ApoE4 mewn clefyd Alzheimer ynghyd â dulliau newydd o fodiwleiddio NMDA a gweithrediad sianel ïonig cainad glwtamad.
Yr hyn sy'n fy ysgogi yw fy awydd i ddatblygu triniaethau newydd ar gyfer anhwylderau niwroddirywiol a seiciatrig sy'n cael effaith enfawr ar gymaint o'n teuluoedd, ac le mae anghenion meddygol sylweddol nad ydynt yn cael eu diwallu.
Bywgraffiad
Ar ôl cwblhau PhD mewn patholeg niwrogemegol yn Adran Patholeg Ysbyty Cyffredinol Newcastle, gweithiais am 5 mlynedd (1984-89) yn Labordy Niwrowyddorau'r Sefydliad Cenedlaethol ar gyfer Oedi ar gampws y Sefydliadu Iechyd Cenedlaethol (NIH) ym Methesda, Maryland, yn astudio newidiadau cyn ac ar ôl marwolaeth mewn niwrogemeg cleifion â chlefyd Alzheimer a syndrom Down.
Yn ystod fy nghyfnod yn NIH, dechreuais brosiect oedd yn edrych ar ddatblygu atalwyr acetylcholinesterase ar gyfer trin clefyd Alzheimer. Yna, ymunais â Chanolfan Ymchwil Niwrowyddorau Merck Sharp a Dohme yn Harlow lle gweithiais rhwng 1989–2006 ar amrywiaeth o agweddau in vitro ac in vivo ar ddarganfod cyffuriau ym maes y niwrowyddorau. Pan gaeodd y safle o ganlyniad anuniongyrchol i'r ffaith y cafodd Vioxx, cyffur pwysig cwmni Merck, ei dynnu oddi ar y farchnad, ymunais â Janssen Pharmaceuticals, sef cangen fferyllol Johnson & Johnson, lle bues yn gweithio rhwng 2006 a 2012 (yn La Jolla i ddechrau, ac yna, oherwydd y cwrw, sglodion a siocled, yn Beerse, Gwlad Belg).
Gadewais y diwydiant fferyllol i ymuno â Phrifysgol Sussex i helpu i sefydlu, gyda'r Athro Simon Ward, Canolfan Darganfod Cyffuriau Sussex, a gyda chymorth yr Athro Martin Gosling hefyd datblygodd y ganolfan enw da am ddarganfod cyffuriau ym maes y niwrowyddorau a ffarmacoleg sianeli ïonig yn benodol.
Yn haf 2017, dewisodd Simon a minnau symud i Gaerdydd. Cawsom ein denu gan y gwaith rhagorol ym maes y mecanwaith clefydau a gwyddorau clinigol, ynghyd ag ansawdd ac ysbryd cydweithredol yr ymchwilwyr y byddwn yn cydweithio â nhw. Fodd bynnag, rydym yn dal i fod mewn cysylltiad â Martin, sy'n gydweithiwr allweddol ac yn ein galluogi i ehangu'r diddordeb sydd gennym mewn ffarmacoleg sianeli ïonig.