GSK256471
GSK256471 is a non-peptide tachykinin NK3 receptor antagonist with a pKi of 8.9 for the human recombinant NK3 receptor and 8.4 for the guinea pig native receptor. GSK256471 exhibits >100-fold selectivity for NK1 (pKi = 5.2) and NK2 (pKi = 7.3) receptors. GSK256471 noncompetitively inhibits neurokinin B (NKB) (HY-P0242)-induced inositol phosphate accumulation, and this inhibition is irreversible. GSK256471 inhibits wet dog shaking behavior and suppresses dopamine release. GSK256471 could be used to study schizophrenia.
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- CAS No.: 1133706-08-7
- Formule: C29H29N3O3S
- Masse moléculaire:499.62
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Stockage:
Please store the product under the recommended conditions in the Certificate of Analysis.
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Activité biologique
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Chemical Information
- Pureté et documentation
- Références
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Help & FAQs
Activité biologique
Description
IC50 & Target
[2]|
NK3R 8.9 (pIC50) |
In Vitro
GSK256471 inhibits the intracellular calcium release induced by NKB with a pKi of 8.9[1].
GSK256471 (0.01-1 μM) causes the NKB concentration-response curve to shift to the right and significantly reduces the maximum response (Emax), indicating the non-competitive antagonistic property in U2OS cells[2].
GSK256471 (0.1-1 μM) completely abolished the neuronal discharge caused by NKB in U2OS cells[2].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
In Vivo
GSK256471 (1 ng/kg-100 mg/kg, i.p., single dose) achieves effective receptor occupation at low brain concentrations with an EC50 of 8 ng/g[2].
GSK256471 (3-30 mg/kg, i.p., single dose) effectively blocks the function of the central NK3 receptor and inhibits the "wet dog shake" behavior in guinea pigs[2].
GSK256471 (1-30 mg/kg, i.p., single dose) regulates the excessive activity of the mesolimbic dopamine system in the brain of guinea pigs, suggesting its potential as an antipsychotic agent[2].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:"Wet dog shake" behavior model established in guinea pig[2]
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Dosage:3, 10 and 30 mg/kg
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Administration:Intraperitoneal injection (i.p.), single dose
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Result:Significantly inhibited behavior at 10 and 30 mg/kg.
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Animal Model:Model of dopamine release in the nucleus accumbens established in guinea pig[2]
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Dosage:0.5, 1, 3, 10 and 30 mg/kg
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Administration:Intraperitoneal injection (i.p.), single dose
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Result:Significantly inhibited dopamine release at 1-10 mg/kg, but the effect disappeared at 30 mg/kg, presenting a "bell-shaped curve".
Chemical Information
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CAS No. 1133706-08-7
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Masse moléculaire 499.62
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Formule C29H29N3O3S
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SMILES
O=C(N[C@H](C1=CC=CC=C1)C2CC2)C3=C(C(C4=CC=CC=C4)=NC5=CC=CC=C35)CN(S(=O)(C)=O)C
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Livraison
Room temperature in continental US; may vary elsewhere.
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Stockage
Please store the product under the recommended conditions in the Certificate of Analysis.
Pureté et documentation
Références
[1]. Smith PW, et al. New quinoline NK3 receptor antagonists with CNS activity. Bioorg Med Chem Lett. 2009 Feb 1;19(3):837-40. [Content Brief]
[2]. Dawson LA, et al. In vitro and in vivo comparison of two non-peptide tachykinin NK3 receptor antagonists: Improvements in efficacy achieved through enhanced brain penetration or altered pharmacological characteristics. Eur J Pharmacol. 2010 Feb 10;627(1-3):106-14. [Content Brief]
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
GSK256471 Related Classifications
HY-116268 Related Classifications
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