3. Drug discoveryDef: The process of drug discovery involves the identification of lead and its targets, synthesis, characterization, screening, and assays for therapeutic efficacy of lead. Once a compound has shown its value in in these tests, it will begin the process of drug development prior to clinical trails.The average time required to bring a drug to the market range from 12â15 years at an average cost of $600â800 million
4. Stages in drug discovery Drug discovery Formulation Preclinical studies Clinical trails Any drug development process must proceed through several stages in order to produce a product that is safe, efficacious, and has passed all regulatory requirements.
6. Drug development Target :Naturally existing cellular or molecular structure involved in the disease pathology on which the drug acts Targets Types Target validation :Involves demonstrating that a molecular target is critically involved in a disease process & modulation of the target is likely to have a therapeutic effect
7. Screening & design Screening :Investigation of a great number of compounds for a particular problem or feature of them Random Screening Non-random Cross Random involves no intellectualization & assays are done with out structural regards Non-random also known as targeted or focused & more narrow approach. compounds having a vague resemblance to weakly active compounds uncovered in a random screened Whether the "hits" against the chosen target will interfere with other related targets - this is the process of cross-screening
8. Techniques in screening High through put screening :ideal technique which involves the molecule finding in such a way that hits only the chosen target even not the related It is often done for a molecule which already has some of the desired properties Virtual high through put screening : where screening is done using computer-generated models and attempting to "dock" virtual libraries to a target, are also often used. This is hit-lead phase is followed
9. Approches Nature of sources Chemical sources Rational approches Molecular modelling Combnitorial chemistry Biotechnology Bioinformatics Preclinical studies Clinicaltrails
19. Nonpeptide LibrariesThe main differences among the various combinatorial approaches are the solid support used, the methods for assembling the building blocks, the state (immobilized or in solution) and numbers (a fraction of the total library or individual entities)
21. Molecular modeling Structure Modifications to Increase Potency and the Therapeutic Index 1 Homologation 2 Chain Branching 3 Ring-Chain Transformations 4 Bioisosterism 5 SAR by NMR/SAR by MS 6 CADD
22. Homologation : prolongation of saturated carbon chain with groups that differ by a constant unit to increase pharmacological effect & lipophilicity Chain branching :this involves the side branching of alkyl groups instead of long straight chain alkyl groups Ring chain transformation :effective pharmacokinetic properties are obtained by transformation of alkyl substituent's into cyclic analogs Bioisosterism :Bioisosterism is an important lead modification approach that has been shown to be useful to attenuate toxicity or to modify the activity of a lead
23. SAR/NMR :This approach, termed SAR by NMR, was initially used to discover compounds with nanomolar affinitiess by tethering two molecules with micro molar affinities (low potency). CADD :Computer-aided design (CAD), also known as computer-aided design and drafting (CADD) , is the use of computer technology for the process of design and design-documentation. Computer Aided Drafting describes the process of drafting with a computer
25. Preclinical studies Acute Studies :The goal is to determine toxic dose levels and observe clinical indications of toxicity. Data from acute toxic studies helps determine doses for repeated dose studies in animals and Phase I studies in humans. Repeated Dose Studies :These are repeated dose studies may be referred to as sub acute, sub chronic, or chronic. The specific duration should anticipate the length of the clinical trial that will be conducted on the new drug. Again, two species are typically required. Genetic Toxicity Studies :These studies assess the likelihood that the drug compound is mutagenic or carcinogenic.
26. Reproductive Toxicity Studies : Segment I reproductive toxic studies look at the effects of the drug on fertility. Segment II and III studies detect effects on embryonic and post-natal development Carcinogenicity Studies :Carcinogenicity studies are usually needed only for drugs intended for chronic or recurring conditions Toxicokinetic Studies :These are typically similar in design to PK/ADME studies except that they use much higher dose levels. They examine the effects of toxic doses of the drug and help estimate the clinical margin of safety
32. Post marketing surveillance : study of uncommon or idiosyncratic ADR dose who occur only after long term use & unsuspected drug interactions Patients treated in the normal course form the study population It includes special cases like pediatrics ,pregnant women renal & hepatic diseased persons who are excluded in the previous stages of clinical trails Modification drug delivery systems ,route of administration, fixed drug doses ,drug combinations etc are explored here
< 2% of new compounds investigated may show suitable biological activityModification of an existing drug can yield as little as 1% suitable compounds< 10% of these compounds result in successful human clinical trials and reaches the market place
Health insurance portability n accountabilityProduct devolp n management associatnCentral drug stndrd controlorganisation
