this presentation is on topic reverse pharmacology which deals with the study from bedside to bench side. it is also aka target-based drug discovery (TDD)
2. Definition
A science of integrating documented experimental hits , into leads
by transdisciplinary exploratory studies and further developing into
drug candidates by experimental research.
In the field of drug discovery, reverse pharmacology also known as
target-based drug discovery (TDD)
3. Reverse pharmacology in India
History
1. Sir Ram Nath Chopra
Father of Indian Pharmacology
Credit for stimulating interest of Indian chemists and pharmacologist in medical plants
2.Sir Gananath Sen
Father of Reverse pharmacology
Laid the foundation of Reverse pharmacology of medicinal plants
4. Scope
• To understand the MOA at multiple levels of biological organization and to
optimize safety, efficacy and acceptability of the leads in natural products,
based on relevant science.
• Paradigm shift from the costly, time consuming, high failure rate
conventional drug discovery to new scientific target based drug discovery
process.
6. 3 Interconnected stages:
• 1) Experiential stage - Identification and documentation (record keeping)
of hits knowledge.
• 2) Exploratory study stage – in vitro and in vivo studies to develop
these hits into leads.
• 3) Experimental stage – to determine safety, efficacy of the candidate drug.
7. Classical versus Reverse Pharmacology
1) Phenotypic-based screening
(or forward approach)
Hit
Lead
Screening
Ligand
Lead optimization
Preclinical studies
If all results are beneficial then only
study go to clinical trial after FDA
approval
2) Costly
3) Need longer time
1)Target-based screening
(or backward approach)
Identification of molecule
(By bioinformatic, genomic, proteomic etc)
Target mining
Screening by binding assay
Ligand fishing
Chemical modification
functional studies to confirm the desired
effects
If results are significant then only study go
to clinical trial after FDA approval
2) More economical
3)Time sparring and success rate is higher
8.
9. Drugs from reverse pharmacology
• Reserpine, an alkaloid isolated from Rauwolfia serpentina, also known as Indian
snakeroot, was a major discovery made by using the reverse pharmacology approach. In
1931, Indian chemists Sen and Bose convincingly demonstrated the antihypertensive and
tranquillizing effects of the plant.
• Later, in 1949, Rustom Jal Vakil, who pioneered the development of cardiology in India,
published a trial of Rauwolfia on patients with essential hypertension, which reported a
reduction in systolic and diastolic blood pressure .
Reserpine as an antihypertensive alkaloid became available in the market as a result of work
carried out by Ciba–Geigy. This was probably the first time the principles of reverse
pharmacology were systematically used for focused, fast-track drug discovery based
on Ayurveda knowledge.
• Artemisinin developed from herb Artemisia annua that was discovered for malaria and also has
anticancer, asthma and antioxidant properties
• Desoris for psoriatic lesion (ointment)
• Picrosides(kutki) in hepatic protection
10.
11. Indian initiative towards progress of Reverse
Pharmacology
•ICMR (IndianCouncil of Medical Research) has recently
established an advanced center of RP at Swami
Prakashananda ayurveda research center, Mumbai (Focus on
diabetes , Musculoskeletal health , malaria, cancer and neuronal plasticity)
•CSIR (Council for Scientific and industrial Research) (trying to
bring industry and academia together)
12. Hurdles
Success stories are very low can be due to:-
1) Absence of technical and scientific contributions from pharmaceutical
companies or govt or other organization
2) Majority of drug discoveries gets significantly delayed
3) Lack of functionally well structured multisystem
4) Isolation and purification process of all of these are very complex
which becomes a bottleneck for drug development
Academia and Industry collaboration would lead to better exploration and
development of medicines
And need to assimilate huge amount of information from biomedical like
genomic and proteomic research into drug discovery programmes.
13. 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
16. Combined network pharmacology and virtual reverse pharmacology
approaches for identification of potential targets to treat vascular
dementia
AlexeyA. Lagunin1,2*, Sergey M. Ivanov1,2,TatyanaA.Gloriozova2, PavelV. Pogodin2, DmitryA.
Filimonov2, Sandeep Kumar3 & Rajesh K.Goel 3* 2020
1 Pirogov Russian National Research Medical University, Department of
Bioinformatics, Moscow, 117997, Russia. 2 Institute of Biomedical Chemistry,
Department of Bioinformatics, Moscow, 119121, Russia. 3 Punjabi University,
Department of Pharmaceutical Sciences and Drug Research, Patiala, 147002, India.
Combined network pharmacology and virtual reverse pharmacology approaches for
identification of potential targets to treat vascular dementia (nih.gov)
Aka Target based drug discovery - TBDD is also particularly useful when there is a proven, strong link between a gene and disease, and this applies not only to monogenic diseases but common illnesses as well.
Neural plasticity" refers to the capacity of the nervous system to modify itself, functionally and structurally, in response to experience and injury.
Traditional knowledge and experimental database can provide new functional leads to reduce time, money and toxicity .
India with its history of natural resources in its health care system, offer immense opportunities
With ayurveda , it becomes clinics to lab
Legacy of traditional ayurveda , modern medicine and scientific technologies, form a golden triangle and by bringing all these together , and becomes “clinics to lab ”
So RP approaches need to be further developed to accelerate the development of newer innovative , safer and effective drugs.