KSC-12-192: Difference between revisions

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;
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;

Browse history interactively

← Previous edit Next edit →

Content deleted Content added

VisualWikitext

Inline

Revision as of 11:53, 21 March 2023

This sandbox is in the article namespace. Either move this page into your userspace, or remove the {{User sandbox}} template.

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	probe 1.1	O	H	CH₃	CF₃
	ML138	KSC-5-240	probe 1	O	H	Cl	Cl
		KSC-12-193	probe 1.3	S	H	CH₃	CF₃
		KSC-5-247G		S	H	Cl	Cl
		KSC-12-238-B5	probe 1.4	O	CH₃	CH₃	CF₃
		KSC-12-238-B4		O	CH₃	Cl	Cl

References

^ Zhou, Lei; Lovell, Kimberly M.; Frankowski, Kevin J.; Slauson, Stephen R.; Phillips, Angela M.; Streicher, John M.; Stahl, Edward; Schmid, Cullen L.; Hodder, Peter; Madoux, Franck; Cameron, Michael D.; Prisinzano, Thomas E.; Aubé, Jeffrey; Bohn, Laura M. (2013-12-20). "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. ISSN 1083-351X. PMC 3868780. PMID 24187130.{{cite journal}}: CS1 maint: unflagged free DOI (link)
^ Tan, Liang; Yan, Wenzhong; McCorvy, John D.; Cheng, Jianjun (2018-11-21). "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. ISSN 1520-4804. PMID 29939744.

[1] Zhou, Lei; Lovell, Kimberly M.; Frankowski, Kevin J.; Slauson, Stephen R.; Phillips, Angela M.; Streicher, John M.; Stahl, Edward; Schmid, Cullen L.; Hodder, Peter; Madoux, Franck; Cameron, Michael D.; Prisinzano, Thomas E.; Aubé, Jeffrey; Bohn, Laura M. (2013-12-20). "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. ISSN 1083-351X. PMC 3868780. PMID 24187130.{{cite journal}}: CS1 maint: unflagged free DOI (link)

[2] Tan, Liang; Yan, Wenzhong; McCorvy, John D.; Cheng, Jianjun (2018-11-21). "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. ISSN 1520-4804. PMID 29939744.

[1]

[2]

@@ Line 27: / Line 27: @@
 KSC-12-192 preferentially activates [[G protein|G-protein]] coupling over [[Arrestin beta 2|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]], are weaker [[Base (chemistry)|bases]], and do not share the heavily [[controlled substance|controlled]] backbones of [[Morphinan|L-morphinans]] or [[Salvinorin|salvinorins]].
+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|triazole]] scaffold (see table), KSC-12-192 had the highest reported potency in vitro as a KOR agonist ([[EC50|EC<sub>50</sub>]] = 31nM<ref>{{Cite journal |last=Tan |first=Liang |last2=Yan |first2=Wenzhong |last3=McCorvy |first3=John D. |last4=Cheng |first4=Jianjun |date=2018-11-21 |title=Biased Ligands of G Protein-Coupled Receptors (GPCRs): Structure-Functional Selectivity Relationships (SFSRs) and Therapeutic Potential |url=https://pubmed.ncbi.nlm.nih.gov/29939744/ |journal=Journal of Medicinal Chemistry |volume=61 |issue=22 |pages=9841–9878 |doi=10.1021/acs.jmedchem.8b00435 |issn=1520-4804 |pmid=29939744}}</ref>).
+Out of a range of tested compounds with the same substituted [[Triazole|triazole]] scaffold (see table), KSC-12-192 had the highest reported in vitro potency as a human KOR agonist ([[EC50|EC<sub>50</sub>]] = 31nM<ref>{{Cite journal |last=Tan |first=Liang |last2=Yan |first2=Wenzhong |last3=McCorvy |first3=John D. |last4=Cheng |first4=Jianjun |date=2018-11-21 |title=Biased Ligands of G Protein-Coupled Receptors (GPCRs): Structure-Functional Selectivity Relationships (SFSRs) and Therapeutic Potential |url=https://pubmed.ncbi.nlm.nih.gov/29939744/ |journal=Journal of Medicinal Chemistry |volume=61 |issue=22 |pages=9841–9878 |doi=10.1021/acs.jmedchem.8b00435 |issn=1520-4804 |pmid=29939744}}</ref>).
 <small>
 {| class="wikitable" style="background-color:white;text-align:center;"

Revision as of 11:53, 21 March 2023

See also

References