KSC-12-192

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 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 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

References

^ 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.
^ 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.

[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.

[1]

[2]

See also

References