KSC-12-192

KSC-12-192 is a drug that is used in scientific research to study the κ-opioid receptor, where it acts as a biased agonist.^[1]

KSC-12-192

Clinical data
Other names	"probe 1.1"
ATC code	None
Identifiers
IUPAC name 2-[4-(furan-2-ylmethyl)-5-[[4-methyl-3-(trifluoromethyl)phenyl]methylsulfanyl]-1,2,4-triazol-3-yl]pyridine
PubChem CID	46245518
IUPHAR/BPS	9191
ChemSpider	58145205
ChEMBL	ChEMBL4458783
Chemical and physical data
Formula	C21H17F3N4OS
Molar mass	430.45 g·mol−1
3D model (JSmol)	Interactive image
SMILES CC1=C(C=C(C=C1)CSC2=NN=C(N2CC3=CC=CO3)C4=CC=CC=N4)C(F)(F)F
InChI InChI=1S/C21H17F3N4OS/c1-14-7-8-15(11-17(14)21(22,23)24)13-30-20-27-26-19(18-6-2-3-9-25-18)28(20)12-16-5-4-10-29-16/h2-11H,12-13H2,1H3 Key:OQJGZGAYSCWFCK-UHFFFAOYSA-N

KSC-12-192 preferentially activates G-protein coupling over β-arrestin 2 recruitment in vitro, an intrinsic activity shared with many other KOR ligands developed to separate KOR-mediated analgesia from accompanying dysphoria.

Compared with most of the known KOR G-protein biased agonists, KSC-12-192 and its parent compound ML138 do not exhibit stereoisomerism.

Out of a range of tested compounds with the same substituted triazole scaffold (see table), KSC-12-192 had the highest reported in vitro potency as a human KOR agonist (EC₅₀ = 31nM^[2]).

Scaffold	Identifiers		X	R1	R2	R3
		KSC-12-192	O	H	CH3	CF3
	ML138	KSC-5-240	O	H	Cl	Cl
		KSC-12-193	S	H	CH3	CF3
		KSC-5-247G	S	H	Cl	Cl
		KSC-12-238-B5	O	CH3	CH3	CF3
		KSC-12-238-B4	O	CH3	Cl	Cl

See also

• Ketazocine
• RB-64
• ICI-199,441
• Spiradoline

References

1. Zhou L, Lovell KM, Frankowski KJ, Slauson SR, Phillips AM, Streicher JM, et al. (December 2013). "Development of functionally selective, small molecule agonists at kappa opioid receptors". The Journal of Biological Chemistry. 288 (51): 36703–36716. doi:10.1074/jbc.M113.504381. PMC 3868780. PMID 24187130.
2. Tan L, Yan W, McCorvy JD, Cheng J (November 2018). "Biased Ligands of G Protein-Coupled Receptors (GPCRs): Structure-Functional Selectivity Relationships (SFSRs) and Therapeutic Potential". Journal of Medicinal Chemistry. 61 (22): 9841–9878. doi:10.1021/acs.jmedchem.8b00435. PMID 29939744. S2CID 49414225.