GSK256471 

GSK256471 is a non-peptide tachykinin NK3 receptor antagonist with a pK_i 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 (pK_i = 5.2) and NK2 (pK_i = 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^[1][2].

GSK256471 inhibits the intracellular calcium release induced by NKB with a pK_i 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 (1-10 mg/kg, i.v., p.o. and i.p., single dose) has moderate brain penetration, but its high affinity compensates for the low exposure dose in rats and gerbils^[1][2].
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.

499.62

C₂₉H₂₉N₃O₃S

1133706-08-7

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

Room temperature in continental US; may vary elsewhere.

Please store the product under the recommended conditions in the Certificate of Analysis.

• [1]. Smith PW, et al. New quinoline NK3 receptor antagonists with CNS activity. Bioorg Med Chem Lett. 2009 Feb 1;19(3):837-40.

  [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.