Serum Glibenclamide in Diabetic Patients, and Influence of Food on the Kinetics and Effects of Glibenclamide is not useful to include for consideration as chemical probe (although is useful to list in extra info for use as clinical biomarker). It would have been more helpful to provide the refs that the data shown were extracted from and these should definitely be listed alongside the probe at the top. The mode of action of these sulfonyl ureas is clearly complex and its understanding has followed the appreciation of their clinical utility. This molecule is clearly able to regulate several ABC transporters by modulation of the K-ATP channels – but there is considerable discussion (e.g. doi: 10.1074/jbc.M110.155200) of block of other related channels – e.g. CFTR.
There is clear evidence that glibenclamide is a wide spectrum KATP blocker [https://pubs.acs.org/doi/pdf/10.1021/jm970762d; European Journal of Medicinal Chemistry 39 (2004) 835–847; Bioorganic & Medicinal Chemistry 11 (2003) 2099–2113) and that different in vivo responses are seen with other related compounds which have a narrower spectrum of KATP block (J. Med. Chem. 2001, 44, 1085-1098).
CFTR is inhibited by glibenclamide and less potently by a few other KATP channel blockers and openers (J Gen. Physiol., 100: 573-591, 1992). Glibenclamide also inhibits MRP1 (Br. J. Pharmacol., 132: 778-784, 2001) and P-gp (Pflugers. Arch., 437: 652-660, 1999), and it appears to be a substrate of the latter.
Therefore, this molecule is a useful blocker of the K-ATP channels (i.e. those containing 4 Kir6.x and 4 SUR subunits) – but there is limited information about the molecular mechanism of differential effects seen in different tissue/organelle type and additional evidence of blockade of other ABC transporters (CFTR, MRP1, PGP).
This is clearly a good probe candidate but from a single publication so far. The best identifier is https://pubchem.ncbi.nlm.nih.gov/compound/103828029. The two melatonic receptor human paralogues are well studied pharmacologically so additional compounds and controls are also available for comparative testing
A curated selected listing of these can be found here https://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=288
2 Jun 2020 )