JAWAHARLAL NEHRU TECHNOLOGICAL UNIVERSITY HYDERABAD

Course Objective

The subject imparts basic knowledge of drug discovery process. This information

will make the student Competent in drug discovery process.

Course Outcome

Upon completion of the course, the student shall be able to,

• Explain the various stages of drug discovery.
• Appreciate the importance of the role of genomics, proteomics and bioinformatics in drug discovery
• Explain various targets for drug discovery.
• Explain various lead seeking method and lead optimization
• Appreciate the importance of the role of computer aided drug design in drug discovery

UNIT - I

An overview of modern drug discovery process: Target identification, target validation, lead identification, and lead Optimization. Economics of drug discovery. Target Discovery and validation- Role of Genomics, Proteomics and Bioinformatics. Role of Nucleic acid microarrays, Protein microarrays, Antisense technologies, siRNAs, antisense oligonucleotides, Zinc finger proteins. Role of transgenic animals in target validation.

UNIT - II

Lead Identification: combinatorial chemistry & high throughput screening, in silico lead discovery techniques; Assay development for hit identification. Protein structure Levels of protein structure, Domains, motifs, and folds in protein structure. Computational prediction of protein structure: Threading and homology modeling methods. Application of NMR and X-ray crystallography in protein structure prediction.

UNIT - III

Rational Drug Design: Traditional vs rational drug design, Methods followed in traditional drug design, High throughput screening, Concepts of Rational Drug Design, Rational Drug Design Methods: Structure and Pharmacophore based approaches. Virtual Screening techniques: Drug likeness screening, Concept of pharmacophore mapping and pharmacophore based Screening,

UNIT - IV

Molecular docking: Rigid docking, flexible docking, manual docking; Docking based screening. De novo drug design. Quantitative analysis of Structure Activity Relationship History and development of QSAR, SAR versus QSAR, Physicochemical parameters, Hansch analysis, Fee Wilson analysis, and relationship between them.

UNIT - V

QSAR Statistical methods: regression analysis, partial least square analysis (PLS) and other multivariate statistical methods. 3D-QSAR approaches like COMFA and COMSIA Prodrug design- Basic concept, Prodrugs to improve patient acceptability, Drug solubility, Drug absorption, and distribution, site specific drug delivery and sustained drug action. Rationale of prodrug design and practical consideration of prodrug design.

REFERENCE BOOKS:

• 1. Mouldy Sioud. Target Discovery and Validation Reviews and Protocols: Volume 2 Emerging Molecular Targets and Treatment Options. 2007 Humana Press Inc.
• 2. Darryl León. Scott MarkelIn. Silico Technologies in Drug Target Identification and Validation 2006 by Taylor and Francis Group, LLC.
• 3. Johanna K. DiStefano. Disease Gene Identification. Methods and Protocols. Springer New York Dordrecht Heidelberg London.
• 4. Hugo Kubiny. QSAR: Hansch Analysis and Related Approaches. Methods and Principles in Medicinal Chemistry. Publisher Wiley-VCH
• 5. Klaus Gubernator, Hans-Joachim Böhm. Structure-Based Ligand Design.
• 6. Methods and Principles in Medicinal Chemistry. Publisher Wiley-VCH
• 7. Abby L. Parrill. M. Rami Reddy. Rational Drug Design. Novel Methodology and Practical Applications. ACS Symposium Series; American Chemical Society: Washington, DC, 1999.
• 8. J. Rick Turner. New drug development design, methodology and, analysis. John Wiley & Sons, Inc., New Jersey.
• 9. Current Concepts in Drug Design,T Durai Ananda Kumar,Pharma Med Press M.Pharm I Year I Sem (Pharmacology)