RESEARCH INTERESTS
Neil Frankish obtained his Ph.D. in pharmacology from the university of Strathclyde, UK. A period of post doctoral research at Leeds University, UK, on the development of the calcium channel blocker bepridil (Vascor) focused his interest on novel drug development. With Assoc. Prof. Helen Sheridan, he is a co-founder of Trino Therapeutics, a commercial spin-out company from the School of Pharmacy. His recent research focus has been on Trino Therapeutics’ proprietary class of drugs made of novel indane dimer derivatives. He has characterised these potential drug candidates in several disease models in the areas of allergy and inflammation and explored their possible applications in a broad range of therapeutic areas. He is a co-inventor of Trino’s key drug class patents and together with Assoc. Prof. Sheridan has been responsible for taking a New Chemical Entity (NCE) from the drawing board through to human subjects.
FINANCIAL SUPPORT
The Wellcome Trust, Fountain Healthcare, Enterprise Ireland, Unimed PLC .
Publications and Further Research Outputs
Peer-Reviewed Publications
Zhang, T. and Scalabrino, G. and Frankish, N. and Sheridan, H., Bioactive indanes: Proof of concept study for enantioselective synthetic routes to ph46a, a new potential anti-inflammatory agent, Molecules, 23, (7), 2018, p1503-
Frankish, N.H. and McHale, B. and Sheridan, H., The indane diastereoisomers, PH2 and PH5: divergence between their effects in delayed-type hypersensitivity models and a model of colitis, Journal of Pharmacy and Pharmacology, 70, (1), 2018, p101-110
Cumming, Graham; Zhang, Tao; Scalabrino, Gaia; Frankish, Neil; Sheridan, Helen, Investigation of the Stereoselective Synthesis of the Indane Dimer PH46A, a New Potential Anti-Inflammatory Agent , Organic Process Research & Development, 2018, p1972-1979
Neil Frankish and helen Sheridan, 'Compounds for use in the treatment of inflammatory Bowel Disease', USP, 9,586,885 B2, 2017, Venantius Ltd.
Nazir I, Ur Rahman N, Alvi Z, Hafizur Rahman M, Sendker J, Zhang T, Frankish N, Sheridan H., Erratum: Antidiabetic Activities of an LC/MS Fingerprinted Aqueous Extract of Fagonia cretica L. in Preclinical Models., Planta medica, 2017
N Frankish, H Sheridan -, 'Compounds for use in the treatment of immune related inflammatory disease', UPTO, 9,586,885, 2017, Venantius
Imran Nazir, Nisar ur Rahman, Zunaira Alvi, M. Hafizur Rahman, Jandirk Sendker, Tao Zhang, Neil Frankish, Helen Sheridan, Antidiabetic Activities of an LC/MS Fingerprinted Aqueous Extract of Fagonia cretica L. in Preclinical Models*, Planta Medica, 83, 2017, p1-9
N Frankish, H Sheridan -, 'Compounds for use in the Treatment of Autoimmune Inflammatory Disease', USPTO, 20,150,141,523,, 2015, Trino Therapeutics Ltd.
Tao Z, Paluch K, Scalabrino G, Frankish N, Healy AM, Sheridan H, Molecular structure studies of (1S,2S)-2-benzyl-2,3-dihydro-2-(1H-inden-2-yl)-1H-inden-1-ol, Journal of Molecular Structure, 2015, p286 - 299
Frankish N, A study to assess the safety and tolerability of PH46A in healthy volunteers, to measure drug levels in these subjects and to determine the effect of food on the drug's absorption, 2014, -
Sheridan, Helen; (IE). Frankish, Neil; (IE), 'indane Dimers for use in the Treatment of Autoimmune Inflammatory Disease', O'BRIEN, John, A, WO/2013/014660 , 2013, VENANTIUS LIMITED
Zhang T, Bandero V, McCabe T, Frankish N, Sheridan H, 2-(Di-phenyl-methyl-idene)-2,3-di-hydro-1H-inden-1-one., Acta crystallographica. Section E, Structure reports online, 69, (Pt 8), 2013, po1306-7
Frampton CS, Zhang T, Scalabrino GA, Frankish N, Sheridan H, (1S)-1-Phenylethanaminium 4-{[(1S,2S)-1-hydroxy-2,3-dihydro-1H,1'H-[2,2'-biinden]-2-yl]methyl}benzoate., Acta crystallographica. Section C, Crystal structure communications, 68, (Pt 8), 2012, po323-6
Zhang T, McCabe T, Marzec B, Frankish N, Sheridan H, N-Cyclo-pentyl-N-(3-oxo-2,3-dihydro-1H-inden-1-yl)acetamide., Acta crystallographica. Section E, Structure reports online, 68, (Pt 4), 2012, po958
Frampton, Christopher S and Zhang, Tao and Scalabrino, Gaia A and Frankish, Neil and Sheridan, Helen, (1S)-1-Phenylethanaminium 4-\{[(1S,2S)-1-hydroxy-2,3-dihydro-1H,1'H-[2,2'-biinden]-2-yl]methyl\, Acta Crystallographica Section C: Crystal Structure Communications, 68, (Pt 8), 2012, po323â"6
Frankish N, Sheridan H, 6-(methylamino)hexane-1,2,3,4,5-pentanol 4-(((1S,2S)-1-hydroxy-2,3-dihydro-1H,1'H-[2,2-biinden]-2-yl)methyl)benzoate (PH46A): a novel small molecule with efficacy in murine models of colitis., Journal of medicinal chemistry, 55, (11), 2012, p5497-505
N Frankish and Helen Sheridan, Venantius Ltd., COMPOUNDS FOR USE IN THE TREATMENT OF INFLAMMATORY BOWEL DISEASE, 2011, 61/510,628
N Frankish and Helen Sheridan, Venantius Ltd., COMPOUNDS FOR USE IN THE TREATMENT OF INFLAMMATORY BOWEL DISEASE, 2011, 61/510,675.
Passante E, Frankish N, Deficiencies in elements involved in TLR4-receptor signalling in RBL-2H3 cells., Inflammation research : official journal of the European Histamine Research Society ... [et al.], 59 Suppl 2, 2010, pS185-6
Frankish, N. de Sousa Menezes, F. Mills, C. Sheridan, H., Enhancement of insulin release from the beta-cell line INS-1 by an ethanolic extract of Bauhinia variegata and its major constituent roseoside, Planta Med, 76, (10), 2010, p995-7
E Passante, C Ehrhardt, H Sheridan, N Frankish, RBL-2H3 cells are an imprecise model for mast cell mediator release, Inflamm Res, 58, (9), 2009, p611-618
Sheridan H, Walsh JJ, Cogan C, Jordan M, McCabe T, Passante E, Frankish NH, Diastereoisomers of 2-Benzyl-2, 3-dihydro-2-(1H-inden-2-yl)-1H-inden-1-ol: Potent anti-inflammatory agents, Bioorganic & Medicinal Chemistry Letters, 19, 2009, p5927 - 5930
Passante, E. Frankish, N., The RBL-2H3 cell line: its provenance and suitability as a model for the mast cell, Inflamm Res, 58, (11), 2009, p737-45
H. Sheridan, N. H. Frankish, BRA 101, A Novel Small Molecule with Profound Efficacy In Murine DSS-Colitis, Gut, Gastro 2009, London, 21-25 November 2009, 58, (Suppl II), 2009, ppA454
Passante, E. Ehrhardt, C. Sheridan, H. Frankish, N., Toll-like receptors and RBL-2H3 mast cells, Inflamm Res, 58 , (Suppl 1), 2009, p11-2
Sheridan, H. Walsh, J. J. Jordan, M. Cogan, C. Frankish, N, A series of 1, 2-coupled indane dimers with mast cell stabilisation and smooth muscle relaxation properties, Eur J Med Chem, 44, (12), 2009, p5018-22
H Sheridan, I Hook, J Coppins, C Nestor, C Ehrhardt, N Frankish, Inhibition of LFA-1 mediated T-cell motility by naphthoquinones, Planta Med, 74, (11), 2008, p1383-1387
J.Coppins, I. Hook, C. Nestor, H. Sheridan, N. Frankish, C. Ehrhardt., Inhibition of LFA-1 mediated T-cell motility by naphthoquinones, Royal Academy of Medicine in Ireland, Winter meeting, Dublin City University, 2007, 2007
Fábio de Sousa Menezes, Andréa Barreto Mattos Minto, Halliny Siqueira Ruela, Ricardo Machado Kuster, Helen Sheridan, Neil Frankish, Hypoglycemic activity of two Brazilian Bauhinia species: Bauhiniaforfi cata L. and Bauhinia monandra Kurz., Brazilian Journal of Pharmacognosy, 17, ((1)), 2007, p8 - 13
Farrell, R., Frankish, N.H.., & Sheridan, H., Synthesis and antispasmodic activity of analogues of Natural pterosins, European Journal of Medicinal Chemistry, 34, 1999, p953 - 966
Sheridan, H., Frankish, N. H. & Farrell, R, Smooth muscle relaxant activity of pterosin Z and related compounds, Planta Medica, 65, 1999, p271 - 272
Anka G Ehrhard, Neil Frankish & Gerrit Isenberg, A large conductance K+ channel that is inhibited by the cytoskeleton in the smooth muscle cell line DDT1 MF-2, Jounal of Physiology, 496, (3), 1996, p663 - 676
H Sheridan, S Lemon, N Frankish, P Mcardle, T Higgins, JP James, P Bhandari , Synthesis and Antispasmodic Activity of Nature Identical Substituted Indanes and Analogues, European Journal of Medicinal Chemistry, 25, (7), 1990, p603 - 608
Frankish, N. H., A low-cost system for on-line analysis of cardiovascular data, British Journal of Pharmacology, 86, 1985, pp762-
Frankish, N. H., Verapamil and bepridil on potassium-evoked contractures of guinea-pig ileum., British Journal of Pharmacology, (80), 1983, pp610-
A. M. Barrett, N. H. Frankish and M. S. Yates, Effect of calcium antagonists on pulmonary haemodynamics, British Journal of Pharmacology, 74, 1981, pp946 - 947
N. H. Frankish and I. J. Zeitlin, The effect of diet on tissue levels on kinin-forming enzyme in blood-free rat gastrointestinal tract, Journal of Physiology, 298, 1980, p361 - 370
Bile may be a stimulus for the activation of duodenal kallikrein during digestion in, editor(s)G. L. Haberland and U. Hamberg. , Current Concepts in Kinin Research, 1978, pp43 - 46, [N. H. Frankish and I. J. Zeitlin]
Bile may be a stimulus for the activation of duodenal kallikrein during digestion in, editor(s)G. L. Haberland and U. Hamberg. , Current Concepts in Kinin Research, 1978, pp43 - 46, [N. H. Frankish and I. J. Zeitlin]
Frankish, N. H. and Zeitlin, I. J., The assay of tissue kallikrein in rat intestine, British Journal of Pharmacology, (59), 1977, pp571-
Frankish NH, Zeitlin IJ., The assay of tissue kallikrein in rat intestine [proceedings]., British journal of pharmacology, 59, (3), 1977, p517P
Frankish NH, Zeitlin IJ., Kallikrein release from rat duodenum stimulation by bile acids and other factors [proceedings], The Journal of physiology, 273, (2), 1977, p60P-61P
Frankish, N. H. and Zeitlin, I. J., Kallikrein release from rat duodenum stimulated by bile acids and other factors, Journal of Physiology, 273, 1977, pp60 - 61
Non-Peer-Reviewed Publications
Neil Frankish and Helen Sheridan, Trino Therapeutics Ltd, 2011
E Passante, C Ehrhardt, H Sheridan, N Frankish, Toll-like receptors and RBL-2H3 mast cells, Inflamm Res, 37th Annual Meeting of the European Histamine Release Society, Stockholm, Sweden, 07-10/05/2008, 58, (S1), 2009, pp11-12
E Passante, C Ehrhardt, H Sheridan, N Frankish, Effect of novel indanes on the degranulation of rat basophilic leukemia mast cells (RBL-2H3), FASEB J, Experimental Biology Meeting 2007, Washington, DC, 28.04.-02.05.2007, 21, (5), 2007, pp574.9
E Passante, S Endter, MH Tindal, MR Pankratz, NH Frankish, C Ehrhardt, Albuterol is net absorbed across human bronchial epithelial cell layers in an enantiomer-dependent fashion, FASEB J, Experimental Biology Meeting 2007, Washington, DC, 28.04.-02.05.2007, 21, (5), 2007, pp881.2
Research Expertise
Description
Current research is largely concerned with finding novel drugs to treat auto-immune inflammatory disease such as inflammatory bowel disease multiple sclerosis and rheumatoid arthritis. Many of the classic immunosuppressive drugs available have a less than satisfactory toxicology profile. More recent monoclonal antibody anti-TNF therapy may be subject to auto-antibody formation and confer susceptibility to opportune infections. The research group concentrates on small molecule inhibitors, novel indane dimer derivatives, and their effects on several systems, including isolated T-cells and mast cells in culture and in vivo disease models. I have been responsible for directing a research program that took a potential drug candidate from its design in Chemdraw to clinical trial. This process included in vitro and in vivo validation studies, assessment in a variety of disease models together with the GLP toxicology and safety studies required for regulatory approval. In addition I was instrumental in designing the clinical trial respecting GCP guidelines, making the Clinical Trial Application to the MHRA and satisfying the Ethics Approval Board prior to the trial. During the clinical trial, I chaired the safety review committee and was responsible for approval for dose escalation in the human subjects. This is an achievement unparalleled in an Irish university.Projects
- Title
- Effect of novel indanes on mast cell function
- Summary
- Novel indanes will be investigated on mast cell function and degrnaulation using harvested peritoneal mast cells, and mast cell lines such as RBL-3H3 and LAD2. Mediators studied will include histamine, cytokines etc.
- Date From
- 1/10/05
- Title
- Assessment of Novel Indanes as potential anti-asthmatic drugs
- Summary
- Novel indane compounds have been studied using mouse and rat bronchoalveolar lavage models of asthma, looking at cell recruitment into the lung, together with cytokine profiles, and their comparison with existing immunosupppression drugs.
- Date From
- 9/2005
- Date To
- 6/2006
- Title
- Studies on LFA-1 stimulated T-cell Motility
- Summary
- A range of novel compounds are being studied on their effects on LFA-1 mediated HUT-78 T-cell motility.
- Date From
- 9/2004
- Title
- Novel indanes as potential therapies for auto-immune disease
- Summary
- Novel indane compounds are being assessed in a variety of in vitro and in vivo models of auto-immune disease.
- Funding Agency
- Commercially funded
- Date From
- 1999
- Title
- Effect of Extracts of Isodon & Bauhinia Species on Inflammation
- Summary
- Extracts of several species of Isodon and Bauhinia are being studied on a range of innflammatory mediators and in vivo inflammatory models.
- Date From
- 10/2005
Recognition
Memberships
British Pharamacologigal Society