olorinab   

GtoPdb Ligand ID: 10058

Synonyms: APD-371 | APD371 | compound 6 [PMID: 29259753]
Compound class: Synthetic organic
Comment: Olorinab (APD371) is a cannabinoid CB2 receptor agonist that is being developed by Arena Pharmaceuticals as a potential treatment for chronic pain [1]. In vitro, APD371 is as efficacious as the CB2 receptor full agonist CP55940 (as determined by measuring and comparing Emax values), and has limited tachyphylaxis liability (i.e. it does cause agonist-induced desensitization due to impeding the return of internalized agonist-activated receptors back to the plasma membrane) .
2D Structure
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Physico-chemical Properties
Hydrogen bond acceptors 5
Hydrogen bond donors 2
Rotatable bonds 6
Topological polar surface area 106.46
Molecular weight 357.18
XLogP 1.19
No. Lipinski's rules broken 0
SMILES / InChI / InChIKey
Canonical SMILES OCC(C(C)(C)C)NC(=O)c1nn(c2c1CC1C2C1)c1ncc[n+](c1)[O-]
Isomeric SMILES OC[C@H](C(C)(C)C)NC(=O)c1nn(c2c1C[C@H]1[C@@H]2C1)c1ncc[n+](c1)[O-]
InChI InChI=1S/C18H23N5O3/c1-18(2,3)13(9-24)20-17(25)15-12-7-10-6-11(10)16(12)23(21-15)14-8-22(26)5-4-19-14/h4-5,8,10-11,13,24H,6-7,9H2,1-3H3,(H,20,25)/t10-,11-,13+/m0/s1
InChI Key ACSQLTBPYZSGBA-GMXVVIOVSA-N
Bioactivity Comments
APD371 is highly selective for CB2 over CB1 in binding and functional assays, and appears to be devoid of CNS activity at CB1 in vivo (indicating peripheral restriction of its activity) [1]. In preclinical testing APD371 was found to be orally active and efficacious in a rat model of osteoarthritis pain.
Selectivity at GPCRs
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Target Sp. Type Action Value Parameter Concentration range (M) Reference
CB2 receptor Hs Agonist Full agonist 8.2 pEC50 - 1
pEC50 8.2 (EC50 6.2x10-9 M) [1]
Description: In a DiscoverX PathHunter β-arrestin recruitment assay.
CB2 receptor Rn Agonist Full agonist 8.1 pEC50 - 1
pEC50 8.1 (EC50 7.6x10-9 M) [1]
Description: In a DiscoverX PathHunter β-arrestin recruitment assay.
CB1 receptor Hs Agonist Agonist <5.0 pEC50 - 1
pEC50 <5.0 (EC50 >1x10-5 M) [1]
Description: In a DiscoverX PathHunter β-arrestin recruitment assay.
CB1 receptor Rn Agonist Agonist <5.0 pEC50 - 1
pEC50 <5.0 (EC50 >1x10-5 M) [1]
Description: In a DiscoverX PathHunter β-arrestin recruitment assay.