Target identification AND ISOLATION OF THERAPEUTIC GENE

STEPS INVOLVED IN DRUG DISCOVERY. M PHARMACY UNIT 1 TOPIC ( PHARMACOLOGY).
USING SUITABLE ANIMAL MODEL AND LATEST TECHNOLOGY IN GENE EXPRESSION AND GENE TARGET .CONDUCTING NEW METHOD AND NEW TECHNOLOGY.

1. Target identification 1. data mining using bio – informatics :- identifying , selecting and prioritizing potential disease target. 2. Choosing the bio chemical pathway :- enzyme or receptor 3. Genetic association :- genetic polymorphism and connection with the disease. 4. Expression profile :- changes in MRNA/PROTEIN LEVEL 5. PATHWAY AND PHENOTYPIC ANALYSIS :- IN-VITRO,CELL BASED MECHANISTIC STUDY. 6.FUNCTION SCREENING :- KNOCK DOWN,KNOCK OUT,TRANSGENIC ANIMALS.

2. ANIMAL PHYSIOLOGICAL EFFECT DRUG

3. TARGET CENTRIC IT STARTS WITH THE IDENTIFICATION OF GENE AND THEIR PROTEIN PRODUCT, WHICH MAY BE ASSOCIATED WITH DISEASE PHENOTYPE. THE GENE WHEN INHIBITED OR ACTIVATED ALLOW RECOGNITION OF THE DISEASE ASSOCIATED WITH IT AND PROVIDES THE OPPORTUNITY FOR THE THERAPEUTIC INTERVENTION. ADVANTAGE AVAILABLITY OF HIGH VALIDITY DISEASE MODEL AND TRANSGENIC ANIMAL FOR IDENTIFICATION OF TARGET.

4. STRUCTURAL BASED TARGET IDENTIFICATION. STRUCTURAL BIOLOGY HAS ENTERD INTO THE DOMAIN OF DRUG DISCOVERY 3 DECADES AGO. THE 3D STRUCTURE OF PROTEIN HAS BEEN DEPOSITED WHICH CAN BE UTILISED FOR DRUG DISCOVERY. SEVERAL DRUG HAD BEEN ORIGINATED FROM STRUCTURE BASED ON APPROACHES ACE; CA INHIBITORS. BASED ON GENETICS LOW THROGHPUT TECHNOLOGY IDENTIFICATION OF DISEASE RELATED GENE . BIOCHEMICAL ASSAY, CELL ASSAY PROTEIN PURIFICATION,GENE CLONING TARGET PREDICTION HIGH

5. KYOTO ENCYCLOPEDIA OF GENE AND GENOMES FOR TARGET IDENTIFICATION. KEGG IS A DATA BASE RESOURCES FOR MOLECULAR LEVEL INFORMATION ESPECIALLY LARGE SCALE MOLECULAR DATA SETS GENERATED BY GENOME SEQUENCING AND OTHER HIGH THROUGH OUT EXPERIMENTAL TECHNOLOGY. TARGET VALIDATION VALIDATED TARGET IS THE ONE THAT CAN BE MANIPULATED WITH DRUG TO PRODUCE POSITIVE CLINICAL EFFECT IN HUMANS. THE CHALLENGE LIES IN DEVELOPING TECHNOLOGY FOR TARGET MANIPULATED RANGING FROM VARIOUS IN VITRO APPROACHES TO ANIMAL MODEL. MULTI STEP PROCESS. SEVERAL TARGET VALIDATION TOOLS ARE AVAILABLE WHICH HELP IN ASSESING THEIR GENETIC ASSOCIATION WITH DISEASE FUNCTION ANALYSIS IN MODEL CELL.

6. ANTI SENSE AGENT :- PREVENT EXPRESSION OF A PROTEIN PRODUCT OF RNA THROUGH INDUCE DEGRADATION VIA RNA. RIBOZYME :- SMALL CATALYTIC RNA MOLECULE THAT CLEAVE OTHER RNA SEQUENCE AT SPECIFIC SITE. ANTI BODY :- MONOCLONAL AB ARE THE MOST PREFERRED TOOLS FOR TARGET VALIDATION, TARGET SPECIFIC PROTEIN AND MOST EFFICIENT IN PROTEIN IDENTIFICATION. PHOTOAMTAMER :- PHOTOREACTIVE NUCLEOTIDE ARE INTRODUCE BY RELATING THYMIDINE WITH BROMODEOXY URIDINE.

7. IN HUMAN TISSUE IN SITU HYBRIDIZATION IMMUNO HISTOCHEMISTRY MICROSCOPY TISSUE ARRAY FUNCTIONAL VALIDATION GENE MANIPULATION PHARMACOLOGY MUTATION OF GENE GENOMIC AND PROTEOMIC POSITIONAL CLONNING MICROARRAY WESTERN BLOTTING

8. MADE BY :- RUPALI SINGH [BHILAI] DRUG DISCOVERY ( TARGET IDENTIFICATION)