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.
For research use only. We do not sell to patients.
- CAS No.: 1133706-08-7
- Formula: C29H29N3O3S
- Molecular Weight:499.62
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Storage:
Please store the product under the recommended conditions in the Certificate of Analysis.
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Biological Activity
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Chemical Information
- Purity & Documentation
- References
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Help & FAQs
Biological Activity
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NK3R 8.9 (pIC50) |
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.
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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Molecular Weight 499.62
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Formula 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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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
Please store the product under the recommended conditions in the Certificate of Analysis.
Purity & Documentation
References
[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)
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