PART-1: DRUG DISCOVERY
A drug is a chemical compound that is in raw form and is used for the purpose of diagnosis, prevention, relief, or cure of disease in humans and animals.
MAIN STAGES OF DRUG DEVELOPMENT PROCESS
- Drug discovery
2. Preclinical Trials
1. DRUG DISCOVERY:
- Drug discovery is the process by which drugs are discovered and designed Identifying a compound therapeutically useful in curing and treating the disease.
- To develop effective and safer drugs
- To develop economical drugs
- To discover new uses of already established drugs.
- To determine the mechanism of drug action
PROCESS OF DRUG DISCOVERY:
- HTS- High throughput screening -Screening more than 50,000 compounds in a day.
- CADD –Computer-Aided Drug Design-Identify lead compound.
- Time-consuming- (10-12 years).
- More expensive to identify one drug maybe it costs around 800 million.
STAGES OF DRUG DISCOVERY:
How the drugs are to be identified?
1. TARGET IDENTIFICATION:
First of all, select the disease and find out the causes of the disease, it may be a genetic disease or environmental disease, or infectious disease.
For example Disease: Tuberculosis
Causes: Mycobacterium tuberculosis. It is a bacterial infection. It is caused by smoking and undernutrition. TB is spread from one person to another through the air.
2. TARGET VALIDATION:
Now, validate the found target it may be gene or protein. Then select the protein to bind the particular randomly selected compounds. Then, validate which protein or gene shows Drug ability. It validates to test more than 50,000 compounds in a day, it is called High throughput screening.
Targeted infection: Mycobacterium tuberculosis. Now, validate more than 1000 compounds to screen the infection, which compound is binding the particular gene and gives drug affinity.
Drugs or chemical compounds that work by binding to specific receptors and activating them are called drug affinity.
3. LEAD IDENTIFICATION:
The chemical compound potential to bind to identify the target successfully.
METHODS OF LEAD IDENTIFICATION.
A. FROM NATURAL SOURCES:
- Plants are considered the primary and the oldest source of drugs.
- ASPIRIN- salix found in willow bark. Aspirin is used for pain relief and antiplatelet drugs.
- COCAINE-It is derived from the coca plant. It is used for anesthesia and recreational drug.
- Digitalis-It is derived from Foxglove (Digitalis Purpurea). Digitalis is used to treat arrhythmia.
- Morphine-It is derived from the Opium poppy(Papaver somniferum)
- Caffeine-Found in coffee beans, tea leaves, cacao pods, kola nuts, and guarana.It is used to treat fatigue and migraines.
B. RANDOM SCREENING/NON-TARGETTED SCREENING:
All compounds including synthetic chemicals, natural products of plants marine, and microbial origin from a given series are tested. In spite of budgetary and manpower overuse, this method may be used to discover drugs or leads that have unexpected activities.
- CYCLOSPORIN was discovered during the screening of fungal products.It is an immunosuppressant drug.
- The drug obtained from the marine organisms which are being conventionally used like shark and cod liver oils,sodium alginate,agar-agar,chitin etc.
- SIMULARIN-source-soft coral sinularia fleibilis.It is used for Anticancer drug.
- ASPERDIOL-source-found in gorgonian coral Eunicea Knighti.It is used for Leukemia.
- VARIABILIN: Source-sponge,Ircinia oros.It is used as an Antibiotic.
Serendipity is when someone accidentally finds something good. Is an unplanned fortunate discovery. Serendipity is also called Happy accident.
- METHOTREXATE (Anticancer drug) –was discovered while studying leukemia and it is being used to treat Psoriasis.
- VINBLASTINE- was first discovered while studying a plant’s antidiabetic effect.
- MUSTIN-discovered in 1940,was used on enemy in wars which is used as an anticancer therapy.
- CISPLATIN-used as a Chemotherapy for Bladder cancer,discovered while studying E.coli bacteria
- INSULIN- was discovered while studying the structure of the pancreas.
D. MOLECULAR MODIFICATION:
Molecular modification is the chemical alteration of a known and previously characterized lead compound for the purpose of enhancing its usefulness as a drug.
Chemical analogs are prepared from already existing drugs by a technique called a molecular modification.
- For example:
- Hydrogenated compound of chlorthiazide exhibits increased potency and less side effects than chlorthiazide.
- ATROPINE ,Changing the slight variation in chemical structure the drug Cocaine discovered.
- Morphine is used as an important agent for the relief of pain.Adding the methane compound and removing hydroxyl compound the drug Codeine was found. Codeine is used for relief mild pain and as an antitussive agent.
4. LEAD OPTIMIZATION:
The new chemical entities discovered by the methods described above are selected and compared with one another and the compound exhibiting greater potency than the existing drugs and which can be developed into a safe and effective medicine is selected. In a simple way, the compound has shortlisted the structure and optimized it. Various in vivo and in vitro tests are performed for comparing the leads to determine their metabolic stability and their effects on the body. The selected chemical compounds were tested in Laboratory methods. Blood and urine samples are analyzed and finally, the compound is therapeutically useful.
Which compound given the therapeutic effect of the particular disease, that chemical compound selected as a medicine.
Article by: Dr.I.Mubashira Pharm.D.