GAT100
GAT100 is a negative allosteric modulator and covalent allosteric probe for cannabinoid receptor type 1 (CB1R). GAT100 acts as a positive allosteric modulator for orthosteric agonist CP55,940 binding to regulate the CB1R signaling pathway. GAT100 reduces the potency and efficacy of orthosteric CB1R agonists in terms of β-arrestin 1 recruitment, phosphorylation of PLCβ3 and ERK1/2, cAMP accumulation, and CB1R internalization. GAT100 is applicable to the research of psychobehavioral and somatic diseases.
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- No. CAS: 1663564-42-8
- Fòrmula: C25H28N4OS
- Peso molecular:432.59
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Actividad biológica
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Cell Line
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Type | Value | Description | References |
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| CHO | EC50 |
19.6 nM
Compound: 20; GAT100
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Positive allosteric modulator activity at human CB1R expressed in CHO cells assessed as enhanced binding of [3H]CP55,940 after 60 mins by liquid scintillation spectrometric analysis
Positive allosteric modulator activity at human CB1R expressed in CHO cells assessed as enhanced binding of [3H]CP55,940 after 60 mins by liquid scintillation spectrometric analysis
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[PMID: 26529344] |
| CHO-K1 | EC50 |
174 nM
Compound: 20; GAT100
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Negative allosteric modulator activity at human CB1R expressed in CHO-K1 cells assessed as effect on CP55,940-induced inhibition of forskolin-induced cAMP accumulation preincubated for 30 mins followed by CP55,940 addition measured for 30 mins by HitHunte
Negative allosteric modulator activity at human CB1R expressed in CHO-K1 cells assessed as effect on CP55,940-induced inhibition of forskolin-induced cAMP accumulation preincubated for 30 mins followed by CP55,940 addition measured for 30 mins by HitHunte
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[PMID: 26529344] |
| CHO-K1 | EC50 |
2.09 nM
Compound: 20; GAT100
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Negative allosteric modulator activity at human CB1R expressed in CHO-K1 cells assessed as inhibition of CP55,940-induced beta-arrestin recruitment preincubated for 30 mins followed by CP55,940 addition measured for 90 mins by PathHunter assay
Negative allosteric modulator activity at human CB1R expressed in CHO-K1 cells assessed as inhibition of CP55,940-induced beta-arrestin recruitment preincubated for 30 mins followed by CP55,940 addition measured for 90 mins by PathHunter assay
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[PMID: 26529344] |
GAT100 (Compound 20) (30 min preincubation, 90 min co-incubation with CP55,940) potently inhibits CP55,940-dependent β-arrestin recruitment and cAMP accumulation in CHO-K1 hCB1R cells, with EC50 values of 2.09 nM and 174 nM, respectively[1].
GAT100 (treated at 37 °C for 60 minutes) acts as a positive allosteric modulator of [3H]CP55,940 binding to CHO hCB1R membranes, with an EC50 of 19.6 nM[1].
GAT100 (500 nM; 0-120 min) covalently labels hCB1R in the cell membrane of HEK293 cells in a time-dependent manner and forms a covalent bond with hCB1R[1].
GAT100 (30 min) potently inhibits CB1-mediated β-arrestin1 recruitment, PLCβ3 phosphorylation, and ERK1/2 phosphorylation in HEK293A, Neuro2a, and STHdhQ7/Q7 cells[2].
GAT100 (1-10000 nM; 4 h) potently inhibits CB1-mediated, forskolin-stimulated cAMP accumulation in HEK-CRE cells[2].
GAT100 (1 μM; 0.5-20 h) rapidly reverses CP55,940-induced CB1 endocytosis in STHdhQ7/Q7 cells, and it restores plasma membrane CB1 levels more rapidly than the reference allosteric modulator[2].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:HEK293A cells transiently transfected with hCB1-GFP2, Neuro2a cells endogenously expressing CB1, STHdhQ7/Q7 cells endogenously expressing CB1
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Concentration:1-10000 nM; 500 nM (co-treated with 2-AG, AEA, or CP55,940)
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Incubation Time:10 min
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Result:Inhibited PLCβ3 phosphorylation in HEK293A cells with IC50 values of 56.1 nM (44.0-62.6 nM, with 2-AG), 50.2 nM (23.9-65.3 nM, with AEA), 76.6 nM (60.8-103 nM, with CP55,940), and Eₘₐₓ values of 0.39, 0.36, 0.39, respectively.
Inhibited PLCβ3 phosphorylation in Neuro2a cells with IC50 values of 50.1 nM (33.4-79.2 nM, with 2-AG), 60.3 nM (28.1-131 nM, with AEA), 49.0 nM (25.2-93.4 nM, with CP55,940), and Eₘₐₓ values of 0.34, 0.37, 0.39, respectively.
Inhibited PLCβ3 phosphorylation in STHdhQ7/Q7 cells with IC50 values of 52.7 nM (39.8-63.1 nM, with 2-AG), 57.4 nM (35.9-66.1 nM, with AEA), 71.0 nM (67.2-79.7 nM, with CP55,940), and Eₘₐₓ values of 0.37, 0.37, 0.38, respectively.
Showed no effect on basal PLCβ3 phosphorylation when tested alone (1 nM to 10 μM) in any cell type.\nInhibited ERK1/2 phosphorylation in HEK293A cells with IC50 values of 69.4 nM (50.2-76.5 nM, with 2-AG), 56.6 nM (29.3-71.6 nM, with AEA), 84.1 nM (78.3-96.1 nM, with CP55,940), and Eₘₐₓ values of 0.33, 0.31, 0.29, respectively.
Inhibited ERK1/2 phosphorylation in Neuro2a cells with IC50 values of 57.5 nM (29.1-112 nM, with 2-AG), 57.5 nM (32.9-72.1 nM, with AEA), 47.9 nM (24.4-94.8 nM, with CP55,940), and Eₘₐₓ values of 0.31, 0.28, 0.33, respectively.
Inhibited ERK1/2 phosphorylation in STHdhQ7/Q7 cells with IC50 values of 57.9 nM (28.4-75.1 nM, with 2-AG), 51.3 nM (19.6-136 nM, with AEA), 52.3 nM (21.8-74.2 nM, with CP55,940), and Eₘₐₓ values of 0.37, 0.32, 0.34, respectively.
Showed no effect on basal ERK1/2 phosphorylation when tested alone (1 nM to 10 μM) in any cell type.
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Cell Line:STHdhQ7/Q7 cells endogenously expressing CB1
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Concentration:1 μM (co-treated with 500 nM CP55,940)
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Incubation Time:0.5 h, 1 h, 5 h, 10 h, 15 h, 20 h
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Result:Reversed CP55,940-induced CB1 internalization, increasing the fraction of CB1 at the plasma membrane to ~0.6 by 0.5 h.
Exhibited a more rapid effect than Org27569 or PSNCBAM-1.
Chemical Information
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No. CAS 1663564-42-8
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Peso molecular 432.59
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Fòrmula C25H28N4OS
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SMILES
O=C(NCCC1=CC=C(C=C1)N2CCCCC2)C=3NC=4C=CC(N=C=S)=CC4C3CC
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Envío
Room temperature in continental US; may vary elsewhere.
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Almacenamiento
Please store the product under the recommended conditions in the Certificate of Analysis.
Pureza y Documentación
Referencias
[1]. Kulkarni PM, et al. Novel Electrophilic and Photoaffinity Covalent Probes for Mapping the Cannabinoid 1 Receptor Allosteric Site(s). J Med Chem. 2016;59(1):44-60. [Content Brief]
[2]. Laprairie RB, et al. Mapping Cannabinoid 1 Receptor Allosteric Site(s): Critical Molecular Determinant and Signaling Profile of GAT100, a Novel, Potent, and Irreversibly Binding Probe. ACS Chem Neurosci. 2016;7(6):776-798. [Content Brief]
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
GAT100 Related Classifications
HY-120093 Related Classifications
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