SLAS News (Jan. 29, 2019) — In the February 2019 issue of SLAS Discovery, a review by researchers from the University of Calabria (Italy) explores OCTNs, a small but intriguing group of transporters that are opening new frontiers in drug design research for improving drug delivery and predicting drug-drug interactions.
OCTNs mediate the flux of physiological organic cations through the plasma membrane of cells. Among the three members of the sub-family, OCTN1 and 2 are present in humans, while OCTN3 was lost during evolution. OCTN2 has a well-established role in maintaining the homeostasis of carnitine, an essential cofactor for producing energy from fatty acid metabolism. Some inherited defects of OCTN2 cause the primary carnitine deficiency, a severe muscle pathology that can be alleviated by administering carnitine as a drug. Noteworthy deficiencies mimicking the disease features can be caused as side effects by some drugs interfering with the carnitine absorption or by a strict vegetarian diet during pregnancy or infancy.
The pathophysiological role of OCTN2 is also confirmed by its presence in exosomes, nanovesicles released in the extracellular environment involved in cell to cell communication. Interestingly, the OCTN1 function remains relatively obscure. In fact, ablation of its gene apparently does not cause any problems in animals. However, some mutations of OCTN1 in humans are associated with inflammatory diseases such as the Crohn's disease.
Studies with the most up to date methodological approaches highlight a link of OCTN1 with inflammation, suggesting that molecules with anti-inflammatory or antioxidant properties might be OCTN1 ligands. In this frame, ergothioneine, a mushroom metabolite and acetylcholine have been proposed. The latter is a well-known neurotransmitter that also plays a role in inflammation via a non-neuronal cholinergic system. Both OCTN1 and OCTN2 show a side function in interaction with cationic drugs. These novel findings open new frontiers in drug design research for improving drug delivery and predicting drug-drug interactions.
“OCTN: A Small Transporter Subfamily with Great Relevance to Human Pathophysiology, Drug Discovery and Diagnostics” can be accessed for free for limited time at https://journals.sagepub.com/doi/full/10.1177/2472555218812821. For more information about SLAS and its journals, visit www.slas.org/journals.
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