BIA-10-2474
In a phase 1 study, BIA 10-2474, an orally administered reversible FAAH inhibitor resulted in acute and rapidly progressive neurologic syndrome developed in three of the four participants starting on the fifth day of drug administration. It was found that BIA 10-2474 and its metabolite BIA 10-2639 exhibited numerous off-targets, including FAAH2 and several lipid hydrolases, such as ABHD6, ABHD11, LIPE, and PNPLA6, and xenobiotic drug-metabolizing enzymes CES1, CES2, and CES3. Some of these off-targets, such as ABHD6 and CES2, were almost completely inhibited (>90%) at both 10 mM BIA 10-2474
General
Type : Pyridine,Imidazole,FAAH inhibitor,Multitarget,Carboxamide
Chemical_Nomenclature : N-cyclohexyl-N-methyl-4-(1-oxidopyridin-1-ium-3-yl)imidazole-1-carboxamide
Canonical SMILES : CN(C1CCCCC1)C(=O)N2C=C(N=C2)C3=C[N+](=CC=C3)[O-]
InChI : InChI=1S\/C16H20N4O2\/c1-18(14-7-3-2-4-8-14)16(21)19-11-15(17-12-19)13-6-5-9-20(22)10-13\/h5-6,9-12,14H,2-4,7-8H2,1H3
InChIKey : DOWVMJFBDGWVML-UHFFFAOYSA-N
Other name(s) : BIA 10-2474,UNII-5AP1ZW859M,5AP1ZW859M,BIA-10-2474,Example 362 [WO2010074588]
MW : 300.36
Formula : C16H20N4O2
CAS_number : 1233855-46-3
PubChem : 46831476
UniChem : DOWVMJFBDGWVML-UHFFFAOYSA-N
IUPHAR :
Wikipedia :
Target
Families : BIA-10-2474 ligand of proteins in family: Carb_B_Chordata || ABHD6-Lip
Stucture :
Protein : human-CES2 || human-ABHD6
References (4)
| Title : Preclinical pharmacological evaluation of the fatty acid amide hydrolase inhibitor BIA 10-2474 - Bonifacio_2020_Br.J.Pharmacol_177_2123 |
| Author(s) : Bonifacio MJ , Sousa F , Aires C , Loureiro AI , Fernandes-Lopes C , Pires NM , Palma PN , Moser P , Soares-da-Silva P |
| Ref : British Journal of Pharmacology , 177 :2123 , 2020 |
| Abstract : Bonifacio_2020_Br.J.Pharmacol_177_2123 |
| ESTHER : Bonifacio_2020_Br.J.Pharmacol_177_2123 |
| PubMedSearch : Bonifacio_2020_Br.J.Pharmacol_177_2123 |
| PubMedID: 31901141 |
| Title : Mapping in vivo target interaction profiles of covalent inhibitors using chemical proteomics with label-free quantification - van Rooden_2018_Nat.Protoc_13_752 |
| Author(s) : van Rooden EJ , Florea BI , Deng H , Baggelaar MP , van Esbroeck ACM , Zhou J , Overkleeft HS , van der Stelt M |
| Ref : Nat Protoc , 13 :752 , 2018 |
| Abstract : van Rooden_2018_Nat.Protoc_13_752 |
| ESTHER : van Rooden_2018_Nat.Protoc_13_752 |
| PubMedSearch : van Rooden_2018_Nat.Protoc_13_752 |
| PubMedID: 29565900 |
| Title : Activity-based protein profiling reveals off-target proteins of the FAAH inhibitor BIA 10-2474 - van Esbroeck_2017_Science_356_1084 |
| Author(s) : van Esbroeck ACM , Janssen APA , Cognetta AB, 3rd , Ogasawara D , Shpak G , van der Kroeg M , Kantae V , Baggelaar MP , de Vrij FMS , Deng H , Allara M , Fezza F , Lin Z , van der Wel T , Soethoudt M , Mock ED , den Dulk H , Baak IL , Florea BI , Hendriks G , De Petrocellis L , Overkleeft HS , Hankemeier T , De Zeeuw CI , Di Marzo V , Maccarrone M , Cravatt BF , Kushner SA , van der Stelt M |
| Ref : Science , 356 :1084 , 2017 |
| Abstract : van Esbroeck_2017_Science_356_1084 |
| ESTHER : van Esbroeck_2017_Science_356_1084 |
| PubMedSearch : van Esbroeck_2017_Science_356_1084 |
| PubMedID: 28596366 |
| Title : Acute Neurologic Disorder from an Inhibitor of Fatty Acid Amide Hydrolase - Kerbrat_2016_N.Engl.J.Med_375_1717 |
| Author(s) : Kerbrat A , Ferre JC , Fillatre P , Ronziere T , Vannier S , Carsin-Nicol B , Lavoue S , Verin M , Gauvrit JY , Le Tulzo Y , Edan G |
| Ref : N Engl J Med , 375 :1717 , 2016 |
| Abstract : Kerbrat_2016_N.Engl.J.Med_375_1717 |
| ESTHER : Kerbrat_2016_N.Engl.J.Med_375_1717 |
| PubMedSearch : Kerbrat_2016_N.Engl.J.Med_375_1717 |
| PubMedID: 27806235 |