RB-64

RB-64

Legal status
Legal status	Legal/Uncontrolled
Identifiers
IUPAC name Methyl (2S,4aR,6aR,7R,9S,10aS,10bR)-2-(furan-3-yl)-6a,10b-dimethyl-4,10-dioxo-9-(2-thiocyanatoacetyl)oxy-2,4a,5,6,7,8,9,10a-octahydro-1H-benzo[f]isochromene-7-carboxylate
CAS Number	1174223-49-4
PubChem CID	73347341
ChemSpider	30812525^Y
UNII	GH7ZNH3JMF
ChEMBL	ChEMBL2381583^Y
CompTox Dashboard (EPA)	DTXSID701031954
Chemical and physical data
Formula	C24H27NO8S
Molar mass	489.54 g·mol^−1
3D model (JSmol)	Interactive image
SMILES C[C@@]12CC[C@H]3C(=O)O[C@@H](C[C@@]3([C@H]1C(=O)[C@H](C[C@H]2C(=O)OC)OC(=O)CSC#N)C)C4=COC=C4
InChI InChI=1S/C24H27NO8S/c1-23-6-4-14-22(29)33-17(13-5-7-31-10-13)9-24(14,2)20(23)19(27)16(8-15(23)21(28)30-3)32-18(26)11-34-12-25/h5,7,10,14-17,20H,4,6,8-9,11H2,1-3H3/t14-,15-,16-,17-,20-,23-,24-/m0/s1^Y[PubChem] Key:AZPUAKGNQXURGA-ZWLNRFIDSA-N^Y[PubChem]

RB-64 is a semi-synthetic derivative of salvinorin A. It is an irreversible agonist, with a reactive thiocyanate group that forms a bond to the κ-opioid receptor (KOR), resulting in very high potency.^[1] It is functionally selective, activating G proteins more potently than β-arrestin-2.^[2] RB-64 has a bias factor of up to 96 and is analgesic with fewer of the side-effects associated with unbiased KOR agonists.^[3] The analgesia is long-lasting. Compared with unbiased agonists, RB-64 evokes considerably less receptor internalization.

See also

• Herkinorin
• Salvinorin B methoxymethyl ether
• Salvinorin A
• Nalfurafine

References

1. Yan F, Bikbulatov RV, Mocanu V, Dicheva N, Parker CE, Wetsel WC, et al. (July 2009). "Structure-based design, synthesis, and biochemical and pharmacological characterization of novel salvinorin A analogues as active state probes of the kappa-opioid receptor". Biochemistry. 48 (29): 6898–6908. doi:10.1021/bi900605n. PMC 2752672. PMID 19555087.
2. White KL, Scopton AP, Rives ML, Bikbulatov RV, Polepally PR, Brown PJ, et al. (January 2014). "Identification of novel functionally selective κ-opioid receptor scaffolds". Molecular Pharmacology. 85 (1): 83–90. doi:10.1124/mol.113.089649. PMC 3868907. PMID 24113749.
3. White KL, Robinson JE, Zhu H, DiBerto JF, Polepally PR, Zjawiony JK, et al. (January 2015). "The G protein-biased κ-opioid receptor agonist RB-64 is analgesic with a unique spectrum of activities in vivo". The Journal of Pharmacology and Experimental Therapeutics. 352 (1): 98–109. doi:10.1124/jpet.114.216820. PMC 4279099. PMID 25320048.