Course

Unit 1

UNIT 1-An overview of the modern drug discovery process: 09 hours

1. Target identification, target validation, lead identification and lead Optimization (3hrs).
2. Economics of drug discovery (1hr).
3. Target Discovery and Validation

1. Role of Genomics, Proteomics and Bioinformatics (1hr).
2. Role of Nucleic acid microarrays, Protein microarrays (1hrs)

• Antisense technologies, siRNAs, antisense oligonucleotides, Zinc finger proteins(2hrs)

1. Role of transgenic animals in target validation (1hrs)

Unit 2

UNIT II-In vitro screening systems in drug discovery process 09 hours

1. Biochemical versus cellular assays (2hr)
2. Assay systems and methods of (2hr)
3. Fluorescence-based assay systems (1hr)
4. Bioluminescence resonance energy transfer assays (1hrs)
5. Electrophysiological patch clamp (1hr)
6. High throughput screening (2hrs)

Unit 3

UNIT III-Lead Identification 09 hours

1. Combinatorial chemistry (2hrs)
2. in silico lead discovery techniques (2hrs)
3. Protein structure:
   1. Levels of protein structure (1hr)
   2. Domains, motifs, and folds in protein structure (1hrs).
4. Computational prediction of protein structure:
   1. Threading and homology modelling methods (1 hr)
   2. Application of NMR and X-ray crystallography in protein structure prediction (1hr)
5. Target prediction by network pharmacology (1 hr)

Unit 4

UNIT IV-Rational Drug Design 09 hours

1. Traditional vs rational drug design (1hr)
2. Methods followed in traditional drug design (1hr)
3. Concepts of Rational Drug Design with examples (1 hr)
4. Rational Drug Design Methods: Structure and Pharmacophore-based approaches (1 hr)
5. Virtual Screening techniques (2hrs)
   1. Drug likeness
   2. Concept of pharmacophore mapping and pharmacophore-based

1. Prodrug Design-Basic concept Rationale of prodrug design and practical consideration (1hr)

Prodrugs to improve.

1. Patient acceptability, Drug solubility, drug absorption and distribution (1hr)
2. Site-specific drug delivery and sustained drug action (1hr)

Unit 5

UNIT V-Molecular docking: 09 hours

1. Prediction and analysis of ADMET properties of new molecules and its importance in drug design (1 hr)
2. Rigid docking, flexible docking, induced fit docking (1hr).
3. Docking-based screening and De novo drug design (1hr)
4. Homology modelling and generation of 3D-structure of protein (2hrs)
5. Concept of pharmacophore
   1. pharmacophore mapping (1hr)
   2. identification of Pharmacophore features (1hr)
   3. Pharmacophore modelling(1hr)
   4. Conformational search used in pharmacophore mapping (1hr)

The field of Drug Discovery, with its principles, holds a pivotal role in the development of new medications and therapies. It encompasses a diverse array of methodologies and techniques, each playing a crucial role in the intricate process of identifying and developing effective treatments. From the meticulous design of molecules in medicinal chemistry laboratories to the large-scale screening of compounds in high-throughput assays, every step in the drug discovery pipeline contributes to the collective endeavor of bringing transformative therapies. It includes a wide range of approaches and strategies, including medicinal chemistry, high-throughput screening, preclinical testing, target validation, and clinical trials.

Drug discovery has a wide and hopeful future because there is a constant demand for new medications to treat a wide range of illnesses. It contributes to the development of novel medications but also significantly advances our knowledge of disease mechanisms, makes personalized medicine possible, and eventually improves global healthcare outcomes. This deeper comprehension paves the way for the realization of personalized medicine, where treatments are tailored to individual genetic and physiological profiles, maximizing efficacy and minimizing adverse effects. Moreover, Drug Discovery fosters collaboration across disciplines and borders, driving forward the frontiers of medical science and ultimately contributing to improved healthcare outcomes on a global scale.

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

KNOWLEDGE

K1 Describe stages in the drug discovery process with explanations.

K2 Enlist fundamental principles of molecular interactions involved in molecular docking

K3 Elaborate rational drug design, incorporating computational, structure-based, and ligand- based approaches.

K4 Compare natural drug sources with modern drug design approaches.

K5 Validate drug targets and comprehend disease pathways at molecular level.

K6 Elucidate modern technologies, and tools in current drug discovery methodologies.

SKILL

S1 Evaluate the effectiveness of a designed drug molecule based on its pharmacokinetic and pharmacodynamic modeling.

S2 Perform virtual screening and molecular docking studies to evaluate the binding affinity of drug candidates

S3 Validate biological targets using advanced technologies

S4 Apply rational design methods including structure-based and pharmacophore-based strategies to develop new drugs

S5 Interpret molecular docking and dynamics results to develop potential lead compounds.

S6 Implement high-throughput screening techniques to identify potential lead compounds.

ATTITUDE

A1 Communicate drug discovery concepts and findings

A2 Manage drug discovery projects, oversee timelines and allocate resources efficiently.

A3 Work effectively in interdisciplinary teams on drug discovery projects.

A4 Develop an attitude of environmental responsibility

A5 Promote a supportive and inclusive environment.

A6 Strive for excellence by setting high standards for oneself

References:

1. Target Discovery and Validation Reviews and Protocols: Volume 2 Emerging Molecular Targetsand Treatment Options. Humana Press Inc. New Jersey; 2007
2. Darryl León. Scott MarkelIn. Silico Technologies in Drug Target Identification and Validation. Taylor and Francis: Florida; 2006
3. Benjamin E. Blass, Basic Principles of Drug Discovery and Development. 2021 2nd Ed. Academic Press, Elsevier UK
4. Johanna DiStefano. Disease Gene Identification. Methods and Protocols. Springer New York Dordrecht Heidelberg: London;2011.
5. Hugo QSAR: Hansch Analysis and Related Approaches. Methods and Principles in Medicinal Chemistry. VCH Publishers: New York; 1993
6. Klaus Gubernator, Hans-Joachim Böhm. Structure-Based Ligand Design. Methods and Principles in Medicinal Chemistry. Publisher Wiley-VCH
7. Abby L .Parrill. M . Rami Rational Drug Design. Novel Methodology and Practical Applications. ACS Symposium Series; American Chemical Society: Washington, DC, 1999.
8. Rick Turner. New drug development design, methodology and, analysis. John Wiley & Sons, Inc., New Jersey.

Journals

1. Drug Discovery Today
2. Nature Chemical Biology
3. Current Drug Targets

Assignments:

1. Discuss the various steps in a drug discovery process with a special on methods adopted in selecting the targets
2. QSAR and its
3. Explore and discuss recently developed anticancer drugs based on
4. Elaborate on the rational approach behind the discovery of any two drugs available in the current market
5. Explain the justification for using the “Lipinski rule of 5” in molecular
6. Elucidating Target Biology and Mechanism of drug Action Across Human Cell-Based Model Systems
7. Cell Biology Methods in Target Validation
8. Bioinformatics approach in predicting the mechanism of drug action
9. List out Various methods and approaches for Rare Disease Drug Discovery