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| Content Provider | frontiers |
|---|---|
| Author | Mohammad Nezhady, Mohammad Ali Chemtob, Sylvain |
| Abstract | HCAR1, commonly known as GPR81, is a G-Protein Coupled Receptor (GPCR) and has been deorphanized more than a decade ago. Lactate is the endogenous ligand of GPR81 and many high potential pharmacological agonists have been developed for its activation. Although some reports mention using 3-hydroxy-butyrate acid (3-OBA) as an antagonist of GPR81 thus inferring GPR81 mediated signaling mechanisms for their observed effects, there is no evidence for such an antagonistic activity in 3-OBA against GPR81. In fact, to this date, there is no report for an antagonist or an inhibitor of GPR81 at all. Whereas 3-OBA is a ligand for HCAR2 (GPR109A)1. In a recent paper, Chen et al used 3-OBA as the antagonist of GPR81 in combination with metformin and PD-1/PD-L1 blockade to demonstrate enhanced antitumor efficacy of later compounds 2. Their whole hypothesis is based on inhibition of GPR81 signaling would increase the efficacy of metformin and PD-1/PD-L1 inhibition. The only method they used is inhibition of GPR81 signaling by 3-OBA to test their hypothesis. They attributed all the observed effects such as cell growth, metabolism, T cell activation, to GPR81 signaling. All of their conclusions are scientifically unfounded as 3-OBA is not a proven antagonist of GPR81 and since they have not used any other experiments to validate the GPR81 mediated effects (e.g. RNAi, knock-out/down). In another recent paper by Yang et al 3, authors use 3-OBA as an antagonist for GPR81 to investigate the ro... |
| ISSN | 16639812 |
| DOI | 10.3389/fphar.2021.803907 |
| Volume Number | 12 |
| Journal | Frontiers in Pharmacology |
| Language | English |
| Publisher Date | 2022-01-03 |
| Access Restriction | Open |
| Subject Keyword | Signalling Lactate 3-hydroxy-butyrate acid GPR81 Antagonist |
| Content Type | Text |
| Resource Type | Article |
| Subject | Pharmacology Pharmacology (medical) |
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