Downloaded 131 times
Uploaded bySachin Jangra
Target identification
This document discusses the key steps in the drug discovery process, including target identification and validation, lead identification, and lead optimization. It describes how identifying the biological target of a disease is the first step, followed by validating that target. Leads are then identified, which are compounds that show desired biological activity against the validated target. The leads undergo optimization to improve properties like potency. Methods for target identification, lead identification, and lead optimization are also outlined.
More Related Content
Similar to Target identification
Target identification
- 1. TARGET IDENTIFICATION & VALIDATION LEADIDENTIFICATION & OPTIMIZATION Presented by :- sachin jangra mPHARMA 2nd SEM Roll no. 5461075
- 2. Identifying thebiological origin of the disease and the potential targets for involvement ,is the first step in the discovery of a medicine.. Target identification is process of identifying the direct molecular target(protein,nucleic acid, or small molecule). INTRODUCTION
- 3. Target Finding aprotein or receptor associated with the disease with which a potential drug interact is known as the TARGET. LEAD A compound usually a small organic molecule that reveal desired biological activity on a validated molecule target.
- 4. Lead identification /optimization isthe one of most important steps in drug development. The chemical structure of lead compound is used as starting point for chemical modification in order to improve potency.
- 6. DRUG DISCOVERY PROCESS Process starts with the identification of a molecular target & then Target validation. The target validation confirms that interaction with the target produce the desired change in the behaviour of diseased cells.
- 7. Characteristics of DRUGTARGET • The drug target is a biomolecule , normally a protein that could exist in complex modality. • The biomolecules have special sites that match other molecule. • Drug bind with the protein reversibly. • Change in the biomolecule/protein structure follow the physiological response.
- 8. Continue…. The physiologicalresponse play a major role in complex regulation & have a therapeutic effect. Biomolecule’s activity, expression & structure might change over duration of pathological process. These small molecule bind to the biomolecule are drugs.
- 9. Role of targetidentification A good target needs to be efficacious, safe, meet clinical and commercial needs and above all, be ‘druggable’. When a biological molecule elicit a biological response which may be measured both in vivo/vitro is known to be a druggable target . A good target identification increased confidence in the relationship between target and disease.
- 10. Approaches to target identification 1.Direct biochemical method 2. Computational inference method 3. Genetic interaction method
- 11. Direct biochemical method Biochemical affinity provides the most direct approach to finding target proteins that bind small molecules of interest. Because they are based on physical interactions involving mammalian or human proteins, biochemical methods can lead to information about molecular mechanisms of efficacy. Direct detection of binding using some washing procedure.
- 12. Computational inference method Comparsionof small molecule to the known reference molecule is done.
- 13. Genetic interfernce method Used to identify protien target . Aim of this method is to compare two or more genomes in order to find the similarities and differences Hence identify potential drug target.
- 14. Lead compound • chemicalcompound that has pharmacological or biological activity and therapeutically useful are the LEAD compound • Organic compounds are identified which interact with the target protein and modulate its activity by using screening approaches. Lead identification
- 15. Methods of leadIdentification I)Random screening: • All compounds including synthetic chemicals, natural products of plant, marine and microbial origin from a given series are tested. • Inspite of budgetary and manpower overuse, this method may be used to discover drugs or leads that have unexpected activities. Streptomycin was founded by this method.
- 16. Methods of leadIdentification ii) Nonrandom screening: It is a modified form of random screening. In this method, only such compounds having similar structural skeletons with that of lead, are tested.
- 17. Methods of leadIdentification iii) Drug metabolism studies : Structural modifications are done in drug molecule by the enzymes to increase its polarity. :-sulfanilamide discovered by metabolic study of prontosil.
- 18. Molecules arechemically modified and characterized in order to obtain compounds with suitable properties to become a drug. Leads are characterized with respect to pharmacodynamic properties such as efficacy and potency in vitro and in vivo, physiochemical properties, and toxicological aspects.
- 19. Methods of LeadOptimization 1. Identification of the active part 2. Functional group optimization. 3. Structure activity relationship studies. 4. Design of rigid analogs
- 20. Identification of theactive part • Any molecule consist of essential and non essential parts. • Essential part is important in governing the pharmacodynamic. • Nonessential part is important in governing the pharmacokinetic. • The relevant group on a molecule that interact with a receptor are known as bioactive functional group.
- 21. • By selectingthe proper functional group , one can govern the drug distribution pattern and can avoid the occuring side effects. Functional group optimization
- 22. Structure activity relationshipstudies • The physiological action of a molecule is a function of its chemical constituent. • This observation is the basis of interpretation of activity in the terms of the structural features of a drug molecule
- 23. TRADITIONAL DRUG DISCOVERY v/s TARGET IDENTIFICATION& VALIDATION LEAD IDENTIFICATION LEAD OPTIMIZATION TARGET IDENTIFICATION& VALIDATION LEAD IDENTIFICATION LEAD OPTIMIZATION Genomic s Data/basi c Research , Assay on Animal In vivo/vitro HTS In vivo/vitro Toxicity assay(in vivo/vitro) Genomic s , Proteomi cs & Bioinformat ics In silico structure based design HTS In vivo/vitro Toxicity assay (in vivo/vitro ) NEW STRATEGIES IN DRUG DISCOVERY
- 24. References… … Shenliang Wang,and Young-Tae Chang ; Tools for target identification and validation; Current Opinion in Chemical Biology 2004, pg. no.371–377 Selzer, P.M., Brutsche and Mullner, H. (2000) Target-based drug discovery for the development of novel antiinfectives. Int. J. Med. Microbiol., pg. no. 290, 191–201. Du GH. Evaluation and validation of drug targets. Acta Pharmacol Sin 2004; pg.no. 1566.