İlaç hedef dışı proteinlerinin tahmini: Aldehit dehidrogenaz inhibitörüyle bir vaka çalışması

Aldehyde dehydrogenases (ALDH) are a large family of enzymes that maintain homeostasis through metabolizing reactive compounds. They play a pivotal role in the regulation of many important biological processes such as detoxification of alcohol and xenobiotics, amino acid salvage pathways, and retinoic acid synthesis. An attractive feature of ALDH is that it is a marker for both normal and cancer stem cells. It is thought to play a role in protection, differentiation and expansion of stem cells. DIMATE, a small molecule inhibitor of ALDH3A1, has been previously shown to display anti-proliferative effects on cancer cells. Drug promiscuity refers to a drug having multiple targets. While multiple targets confer flexibility to a drug, it also creates unintended off-targets. Off-target detection is a crucial step of drug design to prevent unwanted side effects. Reverse docking may be used to identify off-targets, but it is very inefficient and has a high computational cost. An alternative to this is pharmacophore approach. A pharmacophore is a description of the chemical and geometrical features of a compound that is necessary for its interaction with a biological target to initiate or inhibit a biological activity. In this study, we identified the possible off-targets of DIMATE through similarity based approaches employing reverse-docking and through pharmacophore based approaches.