GW438014A free base
GW438014A free base is a selective NPY-Y5 receptor competitive antagonist capable of crossing the blood-brain barrier, with IC50 values of 197 nM and 211 nM against human receptors. GW438014A free base reverses PYY-mediated inhibition of Forskolin (HY-15371)-induced cAMP production, reduces NPY-induced food intake and nocturnal food intake in rodents, decreases body weight gain and fat mass in Zucker rats, and inhibits centrally mediated feeding behavior. GW438014A free base can be used in research related to obesity and epilepsy.
For research use only. We do not sell to patients.
- CAS No.: 469861-48-1
- Formula: C22H19N3O
- Molecular Weight:341.41
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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
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- References
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All Neuropeptide Y Receptor Isoforms
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Biological Activity
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NPY Y5 receptor 197-211 nM (IC50) |
GW438014A free base potently and selectively binds to human Y5 receptors expressed in CHO cell membranes, with a binding IC50 of 211 nM, and shows no affinity for human Y1, Y2, or Y4 receptors at concentrations up to 10,000 nM[1].
GW438014A (10 min) free base acts as a competitive antagonist of human Y5 receptors in HEC-1B cells, reversing PYY-mediated inhibition of Forskolin (HY-15371)-induced cAMP production with a functional IC50 of 197 nM[1].
GW438014A free base is a potent, selective competitive antagonist of human Y5 receptors with minimal activity at other NPY receptor subtypes and unrelated targets[3].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
GW438014A (1-10 mg/kg; i.p.; single dose) free base significantly reduces food intake in 20-hour fasted Sprague-Dawley rats over 3 hours, with minimal effect at lower doses[1].
GW438014A (10 mg/kg; i.p.; single dose) free base significantly inhibits normal dark-cycle food intake in Sprague-Dawley rats over 16 hours[1].
GW438014A (10 mg/kg; i.p.; single dose) free base significantly reduces food intake in fasted ob/ob mice, with 50% inhibition persisting for 24 hours[1].
GW438014A (1-10 mg/kg; i.p.; single dose) free base dose-dependently inhibits overnight dark-cycle food intake in ob/ob mice[1].
GW438014A (10 mg/kg; i.p.; single dose) free base does not block the anticonvulsant effects of the Y5-preferring agonist AlaAibNPY in kainic acid-induced hippocampal seizures in male C57BL/6 mice[2].
GW438014A (10 mg/kg; i.p.; single dose) free base significantly accelerates ventral hippocampal rapid kindling acquisition in male Sprague-Dawley rats, reducing the number of stimuli needed to reach stage 2 by 46%, stage 3 by 48%, and stages 4-5 by 25%, while prolonging afterdischarge durations and increasing generalized seizure frequency during stimulation[3].
GW438014A (10 mg/kg; i.p.; twice daily; 4 days) free base significantly reduces weight gain, food intake, and fat mass in both obese and lean Zucker rats[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:Sprague-Dawley (adult male; hyperphagia model via intracerebroventricular NPY challenge)[1]
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Dosage:3 mg/kg
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Administration:i.p.; single dose
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Result:Produced a statistically significant reduction in NPY-induced cumulative food intake for up to 3 hours post-NPY administration (p < 0.01 for all time points).
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Animal Model:Sprague-Dawley (adult male; hyperphagia model via 20-hour fasting)[1]
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Dosage:1 mg/kg; 3 mg/kg; 10 mg/kg
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Administration:i.p.; single dose
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Result:Had little or no effect on food intake at 1 and 3 mg/kg.
Produced a marked, statistically significant decrease in cumulative food intake over 3 hours at 10 mg/kg (p < 0.05).
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Animal Model:Sprague-Dawley (adult male; tested during dark cycle feeding period)[1]
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Dosage:10 mg/kg
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Administration:i.p.; single dose
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Result:Produced a strong, long-lasting, statistically significant inhibitory effect on cumulative food intake throughout the 16-hour dark period (p < 0.01).
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Animal Model:Zucker (13-week-old; obese and lean; obesity model)[1]
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Dosage:10 mg/kg
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Administration:i.p.; twice daily; 4 days
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Result:Significantly decreased the rate of weight gain in both obese and lean rats compared to vehicle controls (p < 0.05).
Reduced daily food intake by ~20% consistently in both groups.
Significantly reduced fat mass in obese rats (percent change from baseline lower than vehicle controls, p < 0.05) and lean rats (percent change from baseline negative, p < 0.05).
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Animal Model:ob/ob (8-week-old; hyperphagia model via overnight fasting)[1]
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Dosage:10 mg/kg
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Administration:i.p.; single dose
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Result:Produced a marked, statistically significant inhibition of cumulative food intake from 4 to 7 hours post-dosing (p < 0.01).
Maintained 50% inhibition of food intake at 24 hours post-administration.
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Animal Model:ob/ob (8-week-old; tested during dark cycle feeding period)[1]
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Dosage:1 mg/kg; 3 mg/kg; 10 mg/kg
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Administration:i.p.; single dose
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Result:Dose-dependently inhibited overnight food intake.
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Animal Model:C57BL/6 (male, ~60 days old, intrahippocampal kainic acid-induced EEG seizures)[2]
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Dosage:10 mg/kg
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Administration:i.p.; single dose
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Result:Did not alter the ability of the Y5-preferring agonist AlaAibNPY to reduce seizure activity.
Did not affect the 44% reduction in seizure episode number vs. control induced by AlaAibNPY.
Did not affect the 38% reduction in time spent in seizure activity vs. control induced by AlaAibNPY.
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Animal Model:Sprague-Dawley (adult male, 250 g, ventral hippocampal rapid kindling model)[3]
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Dosage:10 mg/kg
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Administration:i.p.; single dose
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Result:Reduced the number of stimuli needed to reach stage 2 by 46% (p<0.05).
Reduced the number of stimuli needed to reach stage 3 by 48% (p<0.05).
Reduced the number of stimuli needed to reach stages 4-5 by 25% (p<0.01).
Increased the number of generalized clonic seizures (stages 4-5) during the stimulation protocol by 60%.
Prolonged mean primary afterdischarge duration from 24.0 s to 54.0 s (p<0.01).
Prolonged mean secondary afterdischarge duration from 24.0 s to 48.0 s (p<0.01).
Showed a similar number of stages 4-5 seizures as vehicle controls (3.3 vs. 4.4) during the 24-hour re-test session.
Chemical Information
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CAS No. 469861-48-1
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Molecular Weight 341.41
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Formula C22H19N3O
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SMILES
O=C(C1=CC=CC=C1)NC2=NC3=C(N2CCC4=CC=CC=C4)C=CC=C3
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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]. Daniels AJ, et al. Food intake inhibition and reduction in body weight gain in lean and obese rodents treated with GW438014A, a potent and selective NPY-Y5 receptor antagonist. Regulatory peptides. 2002 Jun 15;106(1-3):47-54. [Content Brief]
[3]. Benmaamar R, et al. Neuropeptide Y Y5 receptors inhibit kindling acquisition in rats. Regulatory peptides. 2005 Feb 15;125(1-3):79-83. [Content Brief]
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
GW438014A free base Related Classifications
HY-110107A Related Classifications
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