Alex Dean

Small Molecule Inhibitors in Targeted Therapy

Blog Post created by Alex Dean on Apr 9, 2018

In a scenario where cancer has become the Number 1 killer facing all human beings, it’s of increasing importance to find a reliable cure. Though traditional means adopted for cancer treatment such as chemotherapy, radiation therapy and surgery are proved to be effective too, the side effects accompanied by them are also daunting as they do not separate normal cells from cancer cells at all and thus give rise to a series of uncomfortable symptoms. 


To overcome the drawbacks of traditional cancer therapies, tremendous efforts have been made to search for specific molecular targets for selective elimination of cancer cells. The majority of researchers believe that such targeted therapy would conceptually be more specific than the traditional non-targeted therapy. The two main approaches of specific molecular targeting available for use in clinical practice are small molecule agents and monoclonal antibodies (mAbs).


What is small molecule inhibitor?

Simply put, a small molecule inhibitor is a substance that is able to enter cells easily thanks to its low molecular weight. Once inside the cells, it can affect other molecules, such as proteins, and may cause cancer cells to die. This is how small molecule inhibitors work as a targeted therapy. According to relevant statistics, many targeted therapies are small-molecule drugs or small molecule inhibitors.


The difference between monoclonal antibodies and small molecule inhibitors

  1. When compared to monoclonal antibodies which are usually large molecular weight proteins of around 150kDa, small molecule cancer drugs are much smaller in size (500Da) and thus can translocate through plasma membranes. On the contrary, the mAbs can only act on molecules that are expressed on the cell surface.
  2. The small molecule inhibitors are also comparatively cost effective and are amenable to oral administration while the mAbs are mostly administered intravenously.


How does small molecule inhibitor work?

During the last few decades, a number of small molecule drugs have been successfully introduced into the clinic for cancer treatment due to research efforts on molecularly targeted cancer drug discovery. Most of these drugs inhibit critical cancer targets such as serine/threonine/tyrosine kinases, matrix metalloproteinases (MMPs), heat shock proteins (HSPs), proteosome and other proteins playing a role in signal transduction pathways.


Small molecule inhibitors can be used in conjunction with other treatments, such as RNA interference (RNAi), to treat a number of diseases. However, the major difficulty lies in identifying the most specific small-molecule inhibitor associated with disease.