Target Validation Information
Target ID T29683
Target Name Nigral tachykinin NK(3) receptor
Target Type
Investigate
Drug Potency against Target CS-003 Drug Info Ki = 0.74 nM [552800]
PD-157672 Drug Info IC50 = 16 nM
PD-161182 Drug Info IC50 = 7.3 nM
NEUROKININ B Drug Info IC50 = 10 nM
3-methoxy-N',2-diphenylquinoline-4-carbohydrazide Drug Info IC50 = 32 nM [528420]
Talnetant Drug Info Ki = 1 nM [552358]
2-phenyl-N-(1-phenylethyl)quinoline-4-carboxamide Drug Info IC50 = 2200 nM [531249]
PD-160946 Drug Info IC50 = 16 nM
Action against Disease Model Talnetant Two NK3 antagonists, osanetant (SR-142801) and talnetant (SB-223412), have been tested in clinical trials. Both agents are small-molecule, nonpeptide antagonists that inhibit [125I]-MePhe7-NKB binding to the h uMan NK3R (hNK3R) expressed in CHO cell membranes with Kis of 1 nM.In HEK-293 cells expressing the hNK3R, talnetant inhibited the Ca2+ responses induced by IC50 of 6.1nM. [531249] Drug Info
The Effect of Target Knockout, Knockdown or Genetic Variations Capsaicin induced signi?cant increases in blood ?ow(0.2-200 mg in 20 ml)and oedema(2-200 mg in 20 ml).The oedema response was absent in neurokinin-1(NK1)-/- mice and NK1 +/+micetreated with the selective NK1 receptor antagonist SR140333 480 nmol kg-1).The capsaicin-evoked increase in blood ?ow was signi?cantly potentiated in the knockout mice(203% of wild-type response, P<0.05)and wild-type mice treated with SR140333 (201%, P<0.05).The capsaicin-induced increased blood ?ow involves activation of, and possible interactions between,both NK1 and calcitonin generelated peptide 1 receptors. [552800]
References
Ref 552800Novel triple neurokinin receptor antagonist CS-003 strongly inhibits neurokinin related responses. Eur J Pharmacol. 2008 May 31;586(1-3):306-12. doi: 10.1016/j.ejphar.2008.02.056. Epub 2008 Mar 4.
Ref 528420Bioorg Med Chem Lett. 2006 Nov 15;16(22):5748-51. Epub 2006 Sep 6.N',2-diphenylquinoline-4-carbohydrazide based NK3 receptor antagonists.
Ref 552358Development and potential utility of dual and triple NK receptor antagonists. Curr Top Med Chem. 2003;3(12):1410-22.
Ref 531249J Med Chem. 2010 Nov 25;53(22):8080-8. Epub 2010 Nov 3.Virtual screening to identify novel antagonists for the G protein-coupled NK3 receptor.
Ref 531249J Med Chem. 2010 Nov 25;53(22):8080-8. Epub 2010 Nov 3.Virtual screening to identify novel antagonists for the G protein-coupled NK3 receptor.

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