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 |