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
  • 2-[4-(furan-2-ylmethyl)-5-[[4-methyl-3-(trifluoromethyl)phenyl]methylsulfanyl]-1,2,4-triazol-3-yl]pyridine
PubChem CID
ChemSpider
ChEMBL
Chemical and physical data
FormulaC21H17F3N4OS
Molar mass430.45 g·mol−1
3D model (JSmol)
  • CC1=C(C=C(C=C1)CSC2=NN=C(N2CC3=CC=CO3)C4=CC=CC=N4)C(F)(F)F
  • 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]).

ScaffoldIdentifiers X R1 R2 R3
KSC-12-192 OHCH3CF3
ML138KSC-5-240 OHClCl
KSC-12-193 SHCH3CF3
KSC-5-247G SHClCl
KSC-12-238-B5 OCH3CH3CF3
KSC-12-238-B4 OCH3ClCl

See also

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.
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