GSK3787

製品コードS8025 バッチS802501

印刷

化学情報

Synonyms

N/A

Storage
(From the date of receipt)

3 years -20°C powder
1 years -80°C in solvent

化学式

C₁₅H₁₂ClF₃N₂O₃S

分子量

392.78

CAS No.

188591-46-0

Solubility (25°C)*

体外

DMSO

79 mg/mL (201.13 mM)

Water

Insoluble

Ethanol

Insoluble

体内（毎回新しく調製した物を用意してください）

Homogeneous suspension

CMC-NA

≥5mg/ml

Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.

* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

溶剤液（一定の濃度）を調合する

生物活性

製品説明	GSK3787 is a selective and irreversible antagonist of PPARδ with pIC50 of 6.6, with no measurable affinity for hPPARα or hPPARγ.
in vitro	GSK3787 irreversibly antagonizes human and mouse PPARδ that covalently modifies Cys249 within the ligand binding pocket. This compound (1 μM) effectively antagonizes the agonist GW0742 stimulated transcription of CPT1a and PDK4 in human skeletal muscle cells, and effectively antagonize the basal gene expression of CPT1a. It shows no effective antiproliferative activity against colorectal cancer cells. ^[1] This chemical (1 μM) completely antagonizes 50 nM GW0742-induced PPARβ/δ-dependent Angptl4 gene expression in wild-type fibroblasts and in keratinocytes. It (1 μM) largely antagonizes 50 nM GW0742-induced Angptl4 and Adrp mRNAs expression in skin cancer cell A341. This compound (1 μM) largely antagonizes GW0742-induced Angptl4 mRNAs expression in cancer cell lines MCF7 (breast), Huh7 (liver), and HepG2 (liver) cells but not in H1838 or A549 cells (lung). It (1 μM) largely antagonizes GW0742-induced increase of Adrp mRNA in Huh7 and HepG2 cells but not in H1838 cells. This chemical does not antagonize basal expression of either of these two PPARβ/δtarget genes in these cells. Neither GW0742 nor this compound has any effect on cell proliferation of these cells at concentrations ranging from 0.1 to 10 μM. It is able to modulate the association of both PPARβ/δ and PPARγ coregulator peptides in response to ligand activation. Efficacy of this chemical to modulate PPARγ activity is markedly lower than the efficacy of it to act as a PPARβ/δ antagonist. ^[2]
in vivo	GSK3787 antagonizes ligand-induced PPARβ/δ-dependent gene expression in vivo. Oral administration of this compound has no effect on the expression of Angptl4 and Adrp mRNA in mouse colon epithelium. Coadministration of this chemical (10 mg/kg) effectively prevents the GW0742-induced expression of both Angptl4 and Adrp mRNA in wild-type mouse colon epithelium, which is correlated with reduced promoter occupancy of PPARβ/δ on the Angptl4 and Adrp genes. Administration of this compound had no effect on glucose tolerance. ^[2]

製品説明

GSK3787 is a selective and irreversible antagonist of PPARδ with pIC50 of 6.6, with no measurable affinity for hPPARα or hPPARγ.

in vitro

GSK3787 irreversibly antagonizes human and mouse PPARδ that covalently modifies Cys249 within the ligand binding pocket. This compound (1 μM) effectively antagonizes the agonist GW0742 stimulated transcription of CPT1a and PDK4 in human skeletal muscle cells, and effectively antagonize the basal gene expression of CPT1a. It shows no effective antiproliferative activity against colorectal cancer cells. ^[1]

This chemical (1 μM) completely antagonizes 50 nM GW0742-induced PPARβ/δ-dependent Angptl4 gene expression in wild-type fibroblasts and in keratinocytes. It (1 μM) largely antagonizes 50 nM GW0742-induced Angptl4 and Adrp mRNAs expression in skin cancer cell A341. This compound (1 μM) largely antagonizes GW0742-induced Angptl4 mRNAs expression in cancer cell lines MCF7 (breast), Huh7 (liver), and HepG2 (liver) cells but not in H1838 or A549 cells (lung). It (1 μM) largely antagonizes GW0742-induced increase of Adrp mRNA in Huh7 and HepG2 cells but not in H1838 cells. This chemical does not antagonize basal expression of either of these two PPARβ/δtarget genes in these cells. Neither GW0742 nor this compound has any effect on cell proliferation of these cells at concentrations ranging from 0.1 to 10 μM. It is able to modulate the association of both PPARβ/δ and PPARγ coregulator peptides in response to ligand activation. Efficacy of this chemical to modulate PPARγ activity is markedly lower than the efficacy of it to act as a PPARβ/δ antagonist. ^[2]

in vivo

GSK3787 antagonizes ligand-induced PPARβ/δ-dependent gene expression in vivo. Oral administration of this compound has no effect on the expression of Angptl4 and Adrp mRNA in mouse colon epithelium. Coadministration of this chemical (10 mg/kg) effectively prevents the GW0742-induced expression of both Angptl4 and Adrp mRNA in wild-type mouse colon epithelium, which is correlated with reduced promoter occupancy of PPARβ/δ on the Angptl4 and Adrp genes. Administration of this compound had no effect on glucose tolerance. ^[2]

プロトコル(参考用のみ)

キナーゼアッセイ	Saturation binding assay
キナーゼアッセイ	Using 96-well culture plates, 50 nM purified human PPARG LBD and the desired concentration of [³H]GW3738 are diluted to a total volume of 100 μL with buffer consisting of 50 mM KCl, 5 mM EDTA, 10 mM dithiothreitol (DTT), 50 mM HEPES, at pH 7. Saturation binding assays are conducted using concentrations of this compound ranging from 1 to 250 nM. Nonspecific binding at each concentration of [³H]GW3738 is estimated in parallel incubations containing 50 μM unlabeled GW 3738. Plates are incubated for 2 h at room temperature. Free ligand is separated from receptor-bound ligand by size exclusion chromatography using commercially available 96-well format spin columns. Samples (50 μL) from each well of a single test plate are loaded onto a buffer- and temperature-equilibrated 96-well gel filtration block. The block is placed on top of a clean microtiter plate and centrifuged at 1100 g for 4 min. Scintillation fluid (180 ul) is added to each well of the plate containing the eluent, and the plates are sealed and allowed to equilibrate for at least 4 h before counting in a counter. The amount of nonspecific binding at each concentration of [³H]GW3738 is subtracted from all wells and plots of this chemical concentration versus counts per minute (cpm) bound are constructed. The K_d values for [³H]GW3738 are determined from a nonlinear least squares fit of the data to a simple binding model.
細胞アッセイ	細胞株	Cell-free assays
	濃度	6.6
	反応時間
	実験の流れ
動物実験	動物モデル	Male C57BL/6 mice
	投薬量	0.5 mg/kg
	投与方法	i.v.

参考

https://pubmed.ncbi.nlm.nih.gov/20128594/
https://pubmed.ncbi.nlm.nih.gov/20516370/
https://pubmed.ncbi.nlm.nih.gov/9427656/

カスタマーフィードバック

: Data from [Data independently produced by , , Neuropharmacology, 2017, 113(Pt A):396-406]

: Data from [Data independently produced by , , Neuropharmacology, 2016, 113(Pt A):396-406. ]

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Transcription Factor TWIST1 Integrates Dendritic Remodeling and Chronic Stress to Promote Depressive-like Behaviors [ Biol Psychiatry, 2020, S0006-3223(20)31906-5]	PubMed: 33190845
Identification of a rhodanine derivative BML-260 as a potent stimulator of UCP1 expression. [ Theranostics, 2019, 9(12):3501-3514]	PubMed: 31281493

長期の保管のために-20°Cの下で製品を保ってください。

人間や獣医の診断であるか治療的な使用のためにでない。

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