Downloaded 165 times
Uploaded byAnthony Melvin Crasto Ph.D
Drug discovery anthony crasto
This document provides information about Anthony Crasto, a Glenmark scientist based in Navi Mumbai, India. It summarizes that he runs several free websites that provide drug and pharmaceutical information which have received millions of hits on Google. These websites help track new drugs worldwide and provide free advertising to help millions. Despite facing personal challenges with his son's health issues, Crasto's vast readership from academia and industry motivates him to continue his work through these websites.
More Related Content
Similar to Drug discovery anthony crasto
More from Anthony Melvin Crasto Ph.D
Drug discovery anthony crasto
- 1.
- 2. http://newdrugapprovals.wordpress.com/ http://www.allfordrugs.com/ http://worlddrugtracker.blogspot.in/ http://drug-scaleup-and- manufacturing.webnode.com/ http://amcrasto.wordpress.com/ is the link to my blogs which tracks drugs worldwide US, CANADA, JAPAN, EU, CHINA , INDIA ETC
- 3. He was onlyin first standard in school (Dec 2007) when I was Paralysed head to toe. His smiling face sees me through day in and day out. Vast readership from academia and industry motivates me, and keeps me going. Helping millions with free advertisement free websites and has million hits on google Thanks for helping me to keep lionel smiling
- 4. Your ownwill power and determination will reach you to the shore even if you are drowned in the middle of a storm
- 5. Drug discovery Formulation Preclinical studies Clinicaltrails 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. Target Right molecule Candidate drug Preclinical documentatio n Clinical documentation DrugDevelopment 7 years Drug Discovery 5-7 years
- 8. ProductsDrugsTargets & Leads Target selection Target to Lead Lead to candid ate Candidate selection toFTIH FTIH to PoC PoC to Commit to Phase III Phase III File & Launch Lifecycl e mgt 9 - 16 y 12-24m 12-24m 30-33m 8-12m 12-44m 0-30m 18-66m 10-13m Costs ~ $1 billion per successful product
- 9. Compound production Manufacturing 0.5-2 years Preclinical Clinical FDA/EMEAreview Drug Discovery Drug Development Registration Launch PhI PhII PhIII PhIV CD(Candidate Drug) NDA(New Drug Application)
- 10. PhI PhII PhIII DrugDiscovery Drug Development RegistrationPreclinical • GLP (Good Laboratory Practice) • GCP (Good Clinical Practice) • GMP(Good Manufacturing Practice) NDA New Drug Application IND Investigational New Drug (first time in man) Preclinical
- 11. PhI PhII PhIII DrugDiscovery Drug Development RegistrationPreclinical Patents: •Structure class •Compound specific •Synthesis •Indication •Formulation •.... Patent time: •20 years from the filing date •Drug development 10-14 years
- 14. chemical diversity (compound library) test safety&efficacy in animalsand humans gene screen and identify lead Lead optimisation protein target DrugsTargets & Leads Target Validation & Selection Target to Lead (compounds) Lead to candidate Drugs Candidate progress to FTIH and PoC in patients
- 15. Target :Naturally existingcellular 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 •Subject of discovery which include proteins whose is discovered by function basic scientific research New •Have a detailed description of its functions in normal pathology involved in human Established
- 16. Genome Disease Potential DrugTarget Select protein of interest Pathology Link with disease or disease process Selection of Biological Target Genetics Target Selection Approaches to Finding a Drug Target
- 17. Screening :Investigationof 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
- 18. Types ofscreens ◦ Functional assay ◦ Binding assay Cell response Compound binds to cell surface receptor - this can be measured in a “binding assay” This can evoke a cellular response - which can be measured in a “functional assay”
- 19. Nature ofsources Chemical sources Rational approches Molecular modelling Combnitorial chemistry Biotechnology Bioinformatics Preclinical studies Clinicaltrails
- 20. Plant species providea 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 Plant derivatives Marine invertebrates Microbial metabolites
- 21. Ligand based ◦Knowledge of other molecules that bind to the target ◦ Build on known pharmacophore Structure based ◦ Knowledge of three dimensional structure of the target (X-ray or NMR) ◦ Docking
- 22. In vitro ◦Functional cell-based assays (FLIPR) Intracellular calcium mobilization (GCRP) In vivo Species differences! ◦ Potency in vivo? Agonist induced models ( NK1 and NK2) ◦ Effective in IBS? Disease related models
- 23.
- 24. Organic Chemistryinvolved in Synthesis & Purification Organic chemists synthesize new drug compounds as well as isolate and characterize natural products, such as alkaloids. In each case, there is interest in the complex relationships between chemical structure and pharmacological action. The pharmacological activity of a compound is an involved function of the structure, and very small changes may pro- foundly modify the pharmacological effect. These structural modifications may involve replacing one group with another at a specific point in the molecule, shifting the same group from place to place in the parent molecule, saturating valence bonds or modifying the acidity or basicity. Total synthesis is made possible by knowledge of chemical structures and, in many instances, is important economically in reducing the cost of the drug.1 Chromatographic techniques have been widely used for the purification of newly synthesized compounds.
- 25. The firststep in product characterization is to establish the precise chemical identity of the product. It is important to determine whether the material is a compound, i.e. a single chemical entity, a mixture of closely related compounds, mixture of isomers, or merely a loose molecular complex of readily dissociable components. Such information is fundamental to a proper evaluation of the biological properties of the material. For compounds of synthetic origin, identity is usually clearly defined in the great majority of cases by the synthetic route employed. However, it is essential not only that identity be confirmed by alternative means but that the means employed should be capable of providing rapid verification whenever this may be required at any stage of the development program. Modern spectroscopic techniques, such as as1H and 13C NMR and infrared spectroscopy are sensitive tools for such purposes.
- 26. Once anew pharmaceutical lead compound has been discovered, extensive and costly efforts usually are made to prepare a series of analogues in the hope that even better activity will be found. In an effort to improve the efficiency of analogue development, a variety of statistical methods have been introduced. They range from the Hansch approach, in which analysis of variance is used to derive an equation expressing the quantitative relationships between functional group changes and biologic activity, to pattern recognition and factor analysis methods
- 27. Non-clinical riskand benefit assessment for ◦ estimation of an initital safe starting dose in human ◦ to support the clinical program Studies ◦ Pharmacodynamics ◦ Pharmacokinetics ◦ Toxicology Regulatory guidelines Quality requirements Phase I Phase II Phase IIII Registration
- 28. Rat andmouse 2 years dosing Expensive Critical timeline Phase I Phase II Phase IIII
- 29. Topics Lead optimisation– addition of extra properties (ADME) Safety testing Molecules into Medicines Testing in Humans
- 30. Medicinal Chemistry Biolog y Lead compounds fromScreening Candidate selected for testing in man Developability DMPK Hypothesise, design molecules and synthesise Analyse/ rationalise results Test hypothesis
- 31. Chemical source Theseinclude semisynthetic drugs It has organic and inorganic sources Mineral resources are one of it. New source of chemical synthesis is Combinatorial Chemistry 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.
- 32. There differenttypes of combinatorial synthesis combinatorial synthesis Split Synthesis: Peptide Libraries Encoding Combinatorial Libraries Nonpeptide Libraries 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)
- 33. Hit -Lead: Hit confirmation • Re-testing,dose response curve,secondaary screening,chemical amnebilty,biophysical techs &hit ranking and clustering Hit expansion • Affinity, molecular weight and lipophilicity can be linked in single parameter such as ligand efficiency and lipophilic efficiency to assess drug likness Lead optimization • This optimization is accomplished through chemical modification of the hit structure, with modifications chosen by employing SAR as well as structure-based design
- 34. ssssTarget Identification Genetics Molecular Biology Bioinformatics Structure Determination X-rayCrystallography NMR Spectroscopy Computer-Aided Design Molecular Modeling Computer Graphics Biological Assays High-Throughput Screening Computer-Based Screening Synthetic Chemistry Peptidomimetics Combinatorial Chemistry Pre-clinical Trials
- 35. 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.
- 36. Reproductive ToxicityStudies : 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
- 38. Conduct initialnon-clinical safety studies to assess developability and potential risks for first administration to humans Conduct additional studies to build confidence that longer term clinical trials can be conducted safely, and the medicine can be approved for use To complete safety evaluation and assist in dose selection for first clinical trials, Safety Assessment has to:
- 39. Genetic damage? Carcinogenicity? Aspectsof a Safety Assessment One dose Lifetime use Acute Responses Chronic Effects Reproduction Development
- 40. Phase I:No blindingscreening,open label & done in single centre • 20-40 max 50 • Healthy volunteers • Sometimes patients are exposed to drug one by one Number of subjects • Carried out by qualified clinical pharmacologist & trained physician • Dose is given in cumulative manner to achieve the effective dose Associated members • P’kinetics,P’dynamics • Emphasis of safety and tolerability Purpose of study
- 41. Phase II:Therapeutic exploration & dose ranging May be blind or open label (4centre’s or more) • 100-400patients or volunteers • According to specific inclusion and exclusion criteria Number of subjects • Physicians • These are trained as investigators Associated members • To establish therapeutic efficacy of drug ,dosage regimen & ceiling effect in controlled settings • Tolerability & p’cokinetics are studied as phase I extension Purpose of study
- 42. Phase III:Therapeutic confirmation or comparison Done in multicentre • Randamised double blind comparitive trails are done • Indications are finalized & guidelines for therapeutic use are formulated • Submission of NDA for licensing is done who if satisfied grants permission for marketing Number of subjects •500-3000 Associated members • physicians Purpose of study • To establish value of drug in relating to existing one • ADR’S on wide scale in which P’cokinetic data may be obtained
- 43. Chemical Development (CD), incollaboration with Pharmaceutical Development (PD), is charged with delivering a cost effective, efficacious medicine... Drug Substance (DS) Drug Product (DP) Molecules to Medicines
- 44.
- 45. FDA: US Food and Drug Administration EMEA: European Medicines Evaluation Agency MHLW: JapanMinistry of Health Labour & Welfare Agencies provide helpful insight into study design and doses Reduce risk of conducting long, expensive studies that don’t lead to approval May change Phase III clinical plan based on feedback
- 46. Food and Drug Administration European MedicinesAgency Ministry of Health Labour and Welfare Therapeutic Goods Administration Health Canada International Conference on Harmonisation Over 120 ‘International’ markets
- 48. Build onknowledge – creative ideas Scilled medicinal chemists Dedicated project team Serendipity and luck - prepared mind Chemistry Pharmacolog y Toxicolo gy Metabolism PK
- 50. DR ANTHONY MELVINCRASTO Ph.D amcrasto@gmail.com MOBILE-+91 9323115463 GLENMARK SCIENTIST , NAVIMUMBAI, INDIA web link http://anthonycrasto.jimdo.com/ http://www.anthonymelvincrasto.yolasite.com/ http://www.slidestaxx.com/anthony-melvin-crasto-phd https://sites.google.com/site/anthonycrastoorganicchemistry/sites- --my-own-on-the-net http://anthonycrasto.wordpress.com/ http://organicchemistrysite.blogspot.com/ http://www.mendeley.com/profiles/anthony-melvin-crasto/ Congratulations! Your presentation titled "Anthony Crasto Glenmark scientist, helping millions with websites" has just crossed MILLION views.
Editor's Notes
- #8 < 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
- #14 Health insurance portability n accountabilityProduct devolp n management associatnCentral drug stndrd controlorganisation