COMPUTER AIDED DRUG DESIGN: A PARADIGM SHIFT TO RATIONAL DRUG DESIGN (A CASE STUDY OF ALZHEIMER’S DRUG INTERPIRDINE FAILURE)
DOI:
https://doi.org/10.29121/ijetmr.v4.i12.2017.585Keywords:
Drug Discovery, Clinical Trials, Computer Aided Drug Design, Leads, IntepridineAbstract
Drug discovery and design is a tedious and lengthy process which takes enormous time, and
when this process reaches it’s final stage that is the final stage of clinical trials 90% of the
promising drug candidates fail levying a huge financial burden of around $2-3bn on the
developer company. The drug failure not only incurs a financial loss to the company, but also
smashes the hopes of the patients and families waiting for the successful approval of the drug.
The scenario is even complicated when it comes to the drug approval for diseases like
Alzheimer’s. Computer aided drug design may help in the drug discovery process by slashing
the time required for searching the potential drug target through computer aided software and
programs. However the key to the success of the drug still lies in the understanding of the
mechanism of the cause of disease and prognosis. Computer aided drug design help in the
selection and modification of leads out of number of hits available. The present study deals
with a case study of Intepridine an ambitious Axovant drug molecule which failed in the final
phase of clinical trials and was withdrawn from the market by Axovant the developer pharma
company.
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References
Robert Vassan, “BACE1 inhibitor drugs in clinical trials for Alzheimer’s disease”. Alzheimers Res. Ther. 6, 2014,89 DOI: https://doi.org/10.1186/s13195-014-0089-7
H.Crehan, C.A.Lemere, “Anti-Amyloid-β Immunotherapy for Alzhiemer’s Disease”.Developing Therapeutics for Alzheimer’s Disease 2016. DOI: https://doi.org/10.1016/B978-0-12-802173-6.00007-1
Pozzan A. “Molecular descriptors and methods for ligand based virtual high throughput screening in drug discovery”.CurrPharm Des. 12(17), 2006, 2099-2110. DOI: https://doi.org/10.2174/138161206777585247
Green D.V. “Virtual screening of virtual libraries”.Prog Med Chem. 41, 2003, 61-97. DOI: https://doi.org/10.1016/S0079-6468(02)41002-8
Basak S.C. “Chem bio informatics: the advancing frontiers of computer- aided drug design in the post-genmic era”. Curr Comput Aided Drug Des.8, 2012,1-2
UptonN, Chuang T T, Hunter A J, Virley D J. “5-HT6 receptor antagonists as novel cognitive enhancing agents for Alzheimer’s disease”.Neurotherapeutics.5(3), 2008,458-69 DOI: https://doi.org/10.1016/j.nurt.2008.05.008
de Bruin NM, van Drimmelen M, Kops M, van Elk J, Wetering M M, Schwienbacher I. “Effects of risperidone, clozapine and the 5-HT6 antagonist GSK-742457 on PCP –induced deficits in reversal learning in the two lever operant task in male Sprague Dawley rats”. Behav Brain Res. 244, 2013,15-28 DOI: https://doi.org/10.1016/j.bbr.2013.01.035
Callaghan CK, Hok V, Della-Ciesa A, Virley DJ, Upton N, O’ Mara SM. “Age related declines in delayed non-match-to-sample performance (DNMS) are reversed by the novel 5HT6 receptor antagonist SB742457”. Neuropharmacology. 63(5), 2012,890-7 DOI: https://doi.org/10.1016/j.neuropharm.2012.06.034
Codony X, Vela JM, Ramirez MJ. “5-HT6 receptor and cognition”. Curr Opin Pharmacol.11(1), 2011, 94-100 DOI: https://doi.org/10.1016/j.coph.2011.01.004
Ramirez M J. “5HT-6 receptors and Alzheimer’s disease”. Alzheimer Res Ther.5(2), 2013, 15
Marco Biasini, Stefan Bienert, Andrew Waterhouse et.al. “Swiss-Model: modeling protein tertiary and quaternary structure using evolutionary information”. Nucleic Acids Research, 2014; 42 (w1) DOI: https://doi.org/10.1093/nar/gku340
Arnold K, Bordoli L, Kopp J. and Schwede T, “The Swiss- Model workspace:a web-based environment for protein structure homology modeling”. Bioinformatics.22, ,2006, 195-201 DOI: https://doi.org/10.1093/bioinformatics/bti770
Kalpana Virendra Singh, Ramchander Merugu, Jeeven Singh Solanki, “Zika Virus serine Protease complex (NA2B-NS3) inhibition by 2-Amino -5-{[(1Z)-Amino({[(Z)-benzoyl]imino})methyl]amino}-n-(5-amino-7-{[carbamoyl(phenyl)methyl]amino}-6-oxoheptyl) pentanamide, in silico studies”. Asian Journal of Pharmaceutical and Clinical Research.10 (5), 2017, 210-13. DOI: https://doi.org/10.22159/ajpcr.2017.v10i5.17286
Peter Ertl, Bernhard Rohde and Paul Selzer, “Fast Calculation of Molecular Polar Surface Area as a Sum of Fragment –Based Contribution and it’s application to the Prediction of Drug Transport Properties”. J. Med. Chem.43 (20), 2000, 3714-17. DOI: https://doi.org/10.1021/jm000942e
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