Small... Large... Sources of Drugs

Small Molecules as our Drugs

    Initially, most drugs are small organic molecules, typically of molecular weight less than 500 Da. Screening of a "library" of chemicals to find the compound with your features of interest is the usual approach for invention of small molecule drugs. These libraries contain millions of compounds which are screened according their interaction with the specific target or its property to produce a biological response. 

Some of the more than 3,000 drugs at Johns Hopkins. Credit (Brendan Smialowski for The New York Times)

From serendipitous discovery to high throughput screening of libraries, drug discovery has taken a modern approach. The ideal target molecules are of human origin made via transcription and translation of human genes. The 'hit' drugs thus are to react with the human proteins itself rather than their animal counterparts.

    Most of the screened hits require its derivatives to be synthesised for better structure- activity relationship and parameters such as affinity, agonist activity, cell wall permeability, absorption, distribution, and metabolism, its unwanted effects and so on to be optimised. Modern drug development takes to technology like X-ray crystallography, molecular modelling and computational chemistry, NMR, etc., to determine a high-resolution structure of the drugs bound to the target.

    The current era and future heavily depends on computational approach. Developing detailed databases, one with chemical information and another with structural information of millions and millions of drugs. We can just render a drug for its favourable interactions, possibly in a matter of few minutes soon. It can also help to easily discard unwanted ones, predict structural and functional effects of drug binding, even its pharmacokinetic properties. We can even find more uses for already existing drugs and even explain their previous failure in clinical phases.

Now Large Molecules as Drugs...

     Small molecules reigned until recombinant DNA technology came in, helping in protein synthesis by various organisms like bacteria, yeast, and even mammalian cells.  Protein therapeutics now are able to use highly purified humanised protein preparations instead of those derived directly from the animals and all the credit goes to gene cloning technology and large scale protein production via cloned gene expression in bacteria or eukaryotic cells. Even other macromolecules like oligonucleotides can also be used therapeutically.