JPC0323

{{Infobox drug

| drug_name =

| image = JPC0323.svg

| width = 300px

| caption =

| pronounce =

| tradename =

| Drugs.com =

| MedlinePlus =

| licence_CA =

| licence_EU =

| DailyMedID =

| licence_US =

| pregnancy_AU =

| pregnancy_category =

| dependency_liability =

| addiction_liability =

| routes_of_administration =

| class = Serotonin 5-HT_2C and 5-HT_2A receptor positive allosteric modulator

| ATC_prefix = None

| ATC_suffix =

| legal_status =

| bioavailability =

| protein_bound =

| metabolism =

| metabolites =

| onset =

| elimination_half-life =

| duration_of_action =

| excretion =

| CAS_number = 5972-45-2

| CAS_supplemental =

| PubChem = 6453844

| PubChemSubstance =

| IUPHAR_ligand =

| DrugBank =

| ChemSpiderID = 4956192

| UNII =

| KEGG =

| ChEBI =

| ChEMBL = 5397931

| NIAID_ChemDB =

| PDB_ligand =

| synonyms = JPC-0323; N-(1,3-Dihydroxy-2-(hydroxymethyl)propan-2-yl)oleamide

| IUPAC_name = (Z)-N-[1,3-dihydroxy-2-(hydroxymethyl)propan-2-yl]octadec-9-enamide

| C=22 | H=43 | N=1 | O=4

| SMILES = CCCCCCCC/C=C\CCCCCCCC(=O)NC(CO)(CO)CO

| StdInChI = 1S/C22H43NO4/c1-2-3-4-5-6-7-8-9-10-11-12-13-14-15-16-17-21(27)23-22(18-24,19-25)20-26/h9-10,24-26H,2-8,11-20H2,1H3,(H,23,27)/b10-9-

| StdInChIKey = JLFKELVBPUSMGW-KTKRTIGZSA-N

}}

JPC0323, also known as N-(1,3-dihydroxy-2-(hydroxymethyl)propan-2-yl)oleamide, is a dual serotonin 5-HT_2C and 5-HT_2A receptor positive allosteric modulator related to oleamide.{{cite journal | vauthors = Brunetti L, Francavilla F, Leopoldo M, Lacivita E | title = Allosteric Modulators of Serotonin Receptors: A Medicinal Chemistry Survey | journal = Pharmaceuticals (Basel) | volume = 17 | issue = 6 | date = May 2024 | page = 695 | pmid = 38931362 | pmc = 11206742 | doi = 10.3390/ph17060695 | doi-access = free | url = | quote = Several compounds of this series showed significant efficacy at 1 nM in improving 5-HT-mediated calcium efflux. Interestingly, while some of them were selective PAMs of 5-HT2CR, others were described as dual 5-HT2AR/5-HT2CR PAMs. None of these compounds were reported as PAMs of 5-HT2BR. A full characterization was conducted for dual PAM JPC0323 (Figure 6), which evoked a 44% increase in maximum 5-HT-induced Ca2+ intake and also showed negligible displacement at orthosteric binding sites of a number of GPCRs and transporters and exhibited favorable pharmacokinetic parameters. In rats, JPC0323 suppressed spontaneous ambulation in a 5-HT2CR-dependent manner, suggesting that the compound has a preference for 5-HT2CR over 5-HT2AR [75].}}{{cite journal | vauthors = Chen J, Garcia EJ, Merritt CR, Zamora JC, Bolinger AA, Pazdrak K, Stafford SJ, Mifflin RC, Wold EA, Wild CT, Chen H, Anastasio NC, Cunningham KA, Zhou J | title = Discovery of Novel Oleamide Analogues as Brain-Penetrant Positive Allosteric Serotonin 5-HT2C Receptor and Dual 5-HT2C/5-HT2A Receptor Modulators | journal = J Med Chem | volume = 66 | issue = 14 | pages = 9992–10009 | date = July 2023 | pmid = 37462530 | pmc = 10853020 | doi = 10.1021/acs.jmedchem.3c00908 | url = }} It showed negligible affinity for roughly 50{{nbsp}}other targets and did not bind to the orthosteric sites of these receptors. The drug does not affect the serotonin 5-HT_2B receptor.

JPC0323 showed favorable pharmacokinetic properties in preclinical research. It produced hypolocomotion in a serotonin 5-HT_2C receptor-dependent but not serotonin 5-HT_2A receptor-dependent manner in rats, suggesting that it might be a preferential serotonin 5-HT_2C receptor positive allosteric modulator in vivo. The drug was not assessed in terms of head-twitch response, an animal behavioral proxy of psychedelic effects. It is unknown whether it might have hallucinogenic effects via serotonin 5-HT_2A receptor potentiation, but its developers speculated that it might have reduced potential in this regard compared to orthosteric agonists.

JPC0323 was derived as an analogue of the fatty acid amide oleamide and was first described in the scientific literature by 2023. It was described as a "first-in-class" dual serotonin 5-HT_2C and 5-HT_2A receptor positive allosteric modulator.