Principles of drug discovery :                            by kavya lakshmi.v                              (Pharmacology)  ...
Principles of drug discovery<br />
Drug discoveryDef: The process of drug discovery involves the identification of  lead and its targets, synthesis, characte...
Stages in drug discovery<br />                 Drug discovery <br />Formulation  <br />Preclinical studies<br />Clinical t...
Process of drug discovery<br />
Drug development<br />Target :Naturally existing  cellular or molecular structure  involved in the disease pathology on wh...
Screening & design<br />Screening :Investigation of a great number of compounds for a particular problem or feature of the...
 Techniques in screening<br />High through put screening :ideal technique which involves the molecule finding in such a wa...
Approches <br />Nature of sources <br />Chemical sources<br />Rational approches<br />Molecular modelling <br />Combnitori...
Nature of source<br /><ul><li>Plant species provide a potenial source of strating or crude material for the drug discovery
Many cardiotonics are plant derived
 Microbes are the main source of antimicrobial drugs
 Streptomyces species have been a source of antibiotics.
 Marine environments are potential sources for new       bioactive agents.
Arabinose neucleosides discovered from marine invertebates</li></li></ul><li>Chemical source<br />These include semisynthe...
Methods<br />There different types of combinatorial synthesis <br /><ul><li>combinatorial synthesis
 Split Synthesis: Peptide Libraries
 Encoding Combinatorial Libraries
 Nonpeptide Libraries</li></ul>The main differences among the various combinatorial approaches are the solid support used,...
Rational approches<br />Hit -Lead:<br />
Molecular modeling<br />Structure Modifications to Increase Potency and the Therapeutic Index <br />1 Homologation <br />2...
Homologation : prolongation of  saturated carbon chain with groups that differ by a constant unit to increase pharmacologi...
SAR/NMR :This approach, termed SAR by NMR, was initially used to discover compounds with nanomolar affinitiess by tetherin...
Technological Approach<br />ssss<br />
Preclinical studies<br />Acute Studies :The goal is to determine toxic dose levels and observe clinical indications of tox...
Reproductive Toxicity Studies : Segment I reproductive toxic studies look at the effects of the drug on fertility. Segment...
Preclinical studies & Clinical trails<br />
Clinical trails<br />
Clinical trails<br />Phase I:No blinding screening,open label & done in single           centre<br />
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  • &lt; 2% of new compounds investigated may show suitable biological activityModification of an existing drug can yield as little as 1% suitable compounds&lt; 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
  • Principles of drug discovery

    1. 1. Principles of drug discovery : by kavya lakshmi.v (Pharmacology) Under the guidance of : Dr T.Vedhavathi Mpharm ;PhDCmr collage of pharmacy<br />
    2. 2. Principles of drug discovery<br />
    3. 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 12–15 years at an average cost of $600–800 million<br />
    4. 4. Stages in drug discovery<br /> Drug discovery <br />Formulation <br />Preclinical studies<br />Clinical trails<br />Any drug development process must proceed through several stages<br />in order to produce a product that is safe, efficacious, and has passed <br />all regulatory requirements.<br />
    5. 5. Process of drug discovery<br />
    6. 6. Drug development<br />Target :Naturally existing cellular or molecular structure involved in the disease pathology on which the drug acts<br />Targets <br />Types<br />Target validation :Involves demonstrating that a molecular target <br />is critically involved in a disease process & modulation of the <br />target is likely to have a therapeutic effect<br />
    7. 7. Screening & design<br />Screening :Investigation of a great number of compounds for a particular problem or feature of them<br /> Random<br />Screening Non-random<br /> Cross <br />Random involves no intellectualization & assays are done with out structural regards<br />Non-random also known as targeted or focused & more narrow<br /> approach. compounds having a vague resemblance to weakly<br /> active compounds uncovered in a random screened<br /> Whether the "hits" against the chosen target will interfere with other related targets - this is the process of cross-screening<br />
    8. 8. Techniques in screening<br />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<br /> It is often done for a molecule which already has some of the desired properties<br />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.<br />This is hit-lead phase is followed <br />
    9. 9. Approches <br />Nature of sources <br />Chemical sources<br />Rational approches<br />Molecular modelling <br />Combnitorial chemistry<br />Biotechnology<br />Bioinformatics <br />Preclinical studies<br />Clinicaltrails<br />
    10. 10. Nature of source<br /><ul><li>Plant species provide a potenial source of strating or crude material for the drug discovery
    11. 11. Many cardiotonics are plant derived
    12. 12. Microbes are the main source of antimicrobial drugs
    13. 13. Streptomyces species have been a source of antibiotics.
    14. 14. Marine environments are potential sources for new bioactive agents.
    15. 15. Arabinose neucleosides discovered from marine invertebates</li></li></ul><li>Chemical source<br />These include semisynthetic drugs<br />It has organic and inorganic sources<br />Mineral resources are one of it.<br />New source of chemical synthesis is Combinatorial Chemistry<br />Combinatorial chemistry: involves the synthesis or biosynthesis of chemical libraries (a family of compounds having a certain base chemical structure) of molecules with in a short period of time for the purpose of biological screening, particularly for lead discovery or lead modification.<br />
    16. 16. Methods<br />There different types of combinatorial synthesis <br /><ul><li>combinatorial synthesis
    17. 17. Split Synthesis: Peptide Libraries
    18. 18. Encoding Combinatorial Libraries
    19. 19. Nonpeptide Libraries</li></ul>The 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) <br />
    20. 20. Rational approches<br />Hit -Lead:<br />
    21. 21. Molecular modeling<br />Structure Modifications to Increase Potency and the Therapeutic Index <br />1 Homologation <br />2 Chain Branching <br />3 Ring-Chain Transformations <br />4 Bioisosterism<br />5 SAR by NMR/SAR by MS<br />6 CADD<br />
    22. 22. Homologation : prolongation of saturated carbon chain with groups that differ by a constant unit to increase pharmacological effect & lipophilicity<br />Chain branching :this involves the side branching of alkyl groups instead of long straight chain alkyl groups<br />Ring chain transformation :effective pharmacokinetic properties are obtained by transformation of alkyl substituent's into cyclic analogs<br />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<br />
    23. 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). <br />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<br />
    24. 24. Technological Approach<br />ssss<br />
    25. 25. Preclinical studies<br />Acute Studies :The goal is to determine toxic dose levels and observe clinical indications of toxicity. <br />Data from acute toxic studies helps determine doses for repeated dose studies in animals and Phase I studies in humans. <br />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. <br />Genetic Toxicity Studies :These studies assess the likelihood that the drug compound is mutagenic or carcinogenic. <br />
    26. 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<br />Carcinogenicity Studies :Carcinogenicity studies are usually needed only for drugs intended for chronic or recurring conditions<br />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<br />
    27. 27. Preclinical studies & Clinical trails<br />
    28. 28. Clinical trails<br />
    29. 29. Clinical trails<br />Phase I:No blinding screening,open label & done in single centre<br />
    30. 30. Phase II :Therapeutic exploration & dose ranging<br />May be blind or open label (4centre’s or more)<br />
    31. 31. Phase III :Therapeutic confirmation or comparison <br />Done in multicentre<br />
    32. 32. Post marketing surveillance : study of uncommon or idiosyncratic ADR dose who occur only after long term use & unsuspected drug interactions <br />Patients treated in the normal course form the study population <br />It includes special cases like pediatrics ,pregnant women renal & hepatic diseased persons who are excluded in the previous stages of clinical trails<br />Modification drug delivery systems ,route of administration, fixed drug doses ,drug combinations etc are explored here<br />
    33. 33. Novel approaches<br />Micro array techniques<br />Peptidomimetics<br />Pharmacogenomics <br />Proteomics<br />Chemi-informatics<br />
    34. 34. Conclusion<br />
    35. 35. Queries<br />
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