How to Discover New Drugs

Jan 26, 2016

Meng Ling Choong

Group Leader

Experimental Therapeutics Centre

The Experimental Therapeutics Centre (ETC) was set up by the Agency of Science, Technology & Research (A STAR) in 2007 as a centre of excellence to advance and accelerate drug discovery in Singapore. Our primary mission is to guide early stage scientific discoveries towards proof-of-concept in man and translate scientific discoveries into diagnostics and research tools in order to serve unmet medical needs.

I am a member of the Experimental Therapeutics Centre (ETC) in A*STAR. I discover new medicines but I can't do this alone. In drug discovery, we have a big team of scientists divided into many different groups; each with a special role.

Specifically, we discover new cancer drugs and anti microbial drugs. Our Protein Biochemistry Group and Cell-based Assay Development Group will develop assays specific for the cancer or microbes that we want to treat. I work in the high throughput screening (HTS) group. We have half a million small molecules in our possession. Using the aforementioned assays, we will test these molecules one by one to see which one can kill the cells or block a critical target that is needed for the survival of the cells. That is a lot of work. So we have robots helping us. If you come to my lab, you will see the robots hard at work, moving around picking up test plates, dispensing chemicals and so on. It is quite fascinating. This process is known as high throughput drug screening.

When we find a molecule that can kill cancer cells or block a critical target, we call it a hit. We pass the hits to our Medicinal Chemistry Group to study the structure-activity relationship (SAR) of the molecules to their targets. The SAR study will help to make the hit more target-specific and to bind more efficiently to the target. This process improves the physicochemical properties of the hit to make it more drug-like. Eventually we will obtain a lead, which is a promising, optimized hit. Our Preclinical Pharmacology Group will also test the hits and leads for their effects and metabolisms in small animals.

A lead that is ready for human testing is called a Preclinical Development Candidate (PDC). We will pass the PDC to a center known as the Drug Discovery and Development (D3) in A*STAR. D3 will help us to perform Proof-of-Concept (PoC) clinical trials in humans. After PoC, we will out-license the investigational new drug to a major pharmaceutical partner for further development. The funding and partnering with commercial partners will create the opportunity to generate major economic benefit to Singapore.

Working in ETC is one of the most exciting endeavors I have ever undertaken. I get to interact with and bounce ideas off scientists and professionals from diverse backgrounds; from biochemists, cell biologists, medicinal chemists, animal pharmacologists, to clinicians, business development and regulatory affairs specialists. The exposures have certainly deepened my experience, broadened my views, and expanded my horizons beyond basic science to pharmaceutical development. It is very gratifying, and yet humbling, to see the small role that I have played in the cogwheel of events that will bring relief to patients and benefits to the economy.

Dr. Choong Meng Ling leads the High Throughput Screening group in the Experimental Therapeutics Centre, using his knowledge in cell culture and cancer biology to develop and optimize assays for drug screening. He obtained a PhD from NUS and did a post-doctoral fellowship in the Whitehead Institute, MIT. He has previously worked in the Bioprocessing Technology Institute, Isis Pharmaceuticals and Johns Hopkins Singapore.