Finding A Lead Flashcards
What is the drug discovery process
Target identification - lead generations - active to hit - hit to lead - new lead optimisation projects - candidate drug
What is a lead compound
Compound that shows the desired pharmacological activity against a chosen target. Starting point for drug discovery process
Approaches for finding a lead compound
Natural product
Library screening
Evolution of excising drugs
Side effects of existing drugs
What are natural products
Rich source of biologically active compounds that contain an active compound
Example of demand for natural product
It takes 1 true to provide a months supply of taxol for one person. It is now being found in the leaves too
Medical folklore for finding a lead compound
Ancient people depended on local flora ad fauna and can give us clues to high plants might be worth studying ie willow tree for aspirin and opium poppy for morphine
Lead compounds from microorganisms
Bacteria and fungi have evolved t produce Antimicrobial properties. Most drugs are Antimicrobial bar a few.
Ie in a handful of soil there are thousands of bacteria fighting for the habitat and so have produced chemical defences
Lead compound sources from venoms and toxins
Venoms from plant and animals are potent and have specific interactions with macromolecule targets in the body
Ie Brazilian viper for captopril (ACE inhibitor)
Bright frogs don’t produce toxins its the ant they eat and the plants that the ants eat
What is a sensible staring point for a lead compound
The natural ligand of a target receptor
Adrenaline and noradrenaline were lead ompounds for the development of salbutamol `
What are existing libraries
Pharm companies dont throw out the compounds they make. Libraries are full of compounds for testing whenever a new target is studied. Companies also buy from ter libraries. Not the best way
What are me too and me better
Companies modify the structures of existing drugs to develop new drugs within the same market
Luck in finding new lead compound
Serendipity
Siendafil was originally designed a a vasodilator to treat angina and hypertension but showed more effective vasodilation in male genitals than the heart
