Reverse pharmacology
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Transcript of Reverse pharmacology
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REVERSE PHARMACOLOGY&
DRUG DISCOVERY
ILHAR HASHIM, M PHARM-CLINICAL RESEARCHNATIONAL INSTITUTE OF PHARMACEUTICAL EDUCATION AND RESEARCH (NIPER), MOHALI, INDIA-160062
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PHARMACOVIGILANCE: SYSTEMS & METHODOLOGIES ACROSS THE GLOBE
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DEFINITION: Reverse pharmacology is the science of
integrating documented clinical/experiential hits, into leads by transdisciplinary exploratory studies and further developing these into drug candidates by experimental &
clinical research
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SCOPE: The scope of reverse pharmacology is
to understand the mechanisms of action at multiple levels of biological organization and to optimize safety, efficacy and acceptability of the leads in natural products, based on relevant science
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CONCEPT OF REVERSE PHARMACOLOGY The traditional knowledge inspired reverse
pharmacology relates to reversing the routine ‘laboratory to clinic’ progress of discovery pipeline to ‘clinics to laboratories’.
The ayurvedic knowledge database allows drug researchers to start from a well tested and safe botanical material.
Thus in ayurvedic medicine research, clinical experiences, observations or available data becomes a starting point.
In conventional drug research, it comes at the end.
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CONCEPT OF REVERSE PHARMACOLOGY Thus the drug discovery based on ayurveda
follows a ‘reverse pharmacology’ path. Conventional drug discovery path Molecule Mice Men Reverse pharmacology path Man Mice Molecule In this process ‘safety’ remains the most
important starting point and the ‘efficacy’ becomes a matter of validation.
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CONCEPT OF REVERSE PHARMACOLOGY
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CONCEPT OF REVERSE PHARMACOLOGY Traditional medicine
Modern medicine Modern science
Reverse pharmacology is ‘Transdisciplinary’.
Efficient discovery engine
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DRUG DISCOVERY:CURRENT SCENARIO The incredible growth of pharmaceutical
companies due to the discovery of blockbuster drugs is coming to an end.
The average cost and time of discovering, developing and launching a new drug is consistently increasing without an expected corresponding increase in the number of newer, safer and better drugs.
New molecular entities produced per company have declined.
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DRUG DISCOVERY:CURRENT SCENARIO
The strategies that awarded success during the past may not guarantee the same in the future.
So the industry is facing a major challenge to sustain and grow, which is resulting in many merges, acquisitions or closures.
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PHASES OR DOMAINS OF REVERSE PHARMACOLOGY
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PHASES OR DOMAINS OF REVERSE PHARMACOLOGY
So reverse pharmacology is transdisciplinary aspect that is comprised of three phases or domains.
1. Experiential 2. Exploratory
3. Experimental
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EXPERIENTIAL : This phase includes robust
documentation of clinical observations of the biodynamic effects of standardized ayurvedic drugs by meticulous record keeping.
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EXPLORATORY : This phase includes the studies for
tolerability, drug interactions, dose range finding in ambulant patients of defined subsets of the disease and paraclinical studies in relevant invitro & invivo models to evaluate the target activity.
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EXPERIMENTAL : In basic & clinical, at several levels of
biological organisation, to identify and validate the reverse pharmacological correlates of ayurvedic drug safety and efficacy.
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DRUGS FROM REVERSE PHARMACOLOGY PATH
ARTEMISININ The artemisinin was developed from
the herb Artemisia annua that has been used for many centuries in Chinese traditional medicine as a treatment for fever and malaria.
Now artimisinin and its derivatives offer a promise as a totally new class of antimalarials.
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DESORIS This drug candidate is a herbal beneficiated
extract of a single plant that has a novel mechanism of action and effectively modulates the cellular function leading to psoriatic lesion improvement.
Lupin commenced the phase1 clinical trial in september 2004 successfully completed it.
If successful, the resulting treatment with Desoris only cost US $ 50, when compared to new US $ 20,000 antibody injection treatment.
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Rauwolfia alkaloids for hypertension.
Psoralens in Vitiligo.
Holarrhena alkaloids in Amoebiasis.
Picrosides in hepatic protection etc…
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REVERSE PHARMACOLOGY: HURDLES Despite a vast potential and possibilities very
few success stories are available till now. Most of the work in this field has remained
within clinics of traditional practitioners and are not taken by industries that are strong in research and development.
The pharmaceutical industry needs many more successes like artemisinin & reserpine.
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FUTURE PERSPECTIVES Many countries are increasingly aware of the
value of their traditional knowledge. Global pharmaceutical industry is looking for
innovative solutions to re-activate and re-energize their discovery pipeline.
Therefore, innovative approaches inspired by traditional knowledge will remain important to fast forward the discovery process
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CONCLUSION Traditional knowledge and experiential database
can provide new functional leads to reduce time, money and toxicity – the three main hurdles in the drug development .
These records are particularly valuable since those medicines have been effectively tested for thousands of years on people .
With the reverse pharmacology approach, the normal drug discovery course of ‘Laboratory to clinics’ becomes from ‘Clinics to Laboratories’.
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India with its pluralistic health care system offers immense opportunities for natural product drug discovery and development based on traditional knowledge and clinical observations.
So reverse pharmacology approaches need to be further developed and optimized as novel means for fast track drug discovery and development of newer, safer & effective drugs.
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THANK YOU