Recently i asked this question to a pHD student who has targeted a protein which is involved in splicing, and overexpression of it has been linked to cancer .
Now, i questioned him that, the protein that he has targeted is present in every cell , if he inhibits the activity of that particular protein in cancer cells wont the normal cells be affected because the normal cells also have this protein.
To this he replied " NO" the normal cells wont be affected . the drug will only bind to the cells where that particular protein is being over expressed (i.e Cancer cells)
No the drugs are not specific, he is just screening the compounds ( in silico) and will proceed to in vitro if good binding affinity is found (in silico).
How much of this is true?
This is essentially the reliant hypothesis for many cancer targets that are overexpresssed in mutated but not normal cells. Assuming unaltered proteomics, the hope is that titrating exposure will favor cancer cell effect over on-target toxicity. A good example is inhibiting nutrient transporters that are overexpressed. I am unaware of success in finding a GLUT1 inhibitor that selectively avoids inhibition of glucose transport at the blood-brain barrier. It's all abt the target and how critical it is in adult/mature cells where sometimes rescue or alternate pathways are present or expression is markedly suppressed. Consequently, target selection often involves knowing the consequence of target knockout.
It is more likely that the drug binds a fixed proportion of all the protein molecules, whichever cell they are in, e.g. 50% if the dose is the IC50. If overexpression is a key mechanism of the cancer (rather than a side effect), then the drug will impact the cancer. However, inhibition of the protein in normal cells will lead to drug side effect - that is why chemotherapy is often noncompassionate.
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