GSK3787

製品コードS8025 バッチS802502

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
* <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. GSK 3787 completely antagonizes the activity of agonist GW501516 with a pIC50 of 6.9 and 94% maximal inhibition. GSK3787 (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. GSK 3787 shows no effective antiproliferative activity against colorectal cancer cells. ^[1] GSK3787 (1 μM) completely antagonizes 50 nM GW0742-induced PPARβ/δ-dependent Angptl4 gene expression in wild-type fibroblasts and in keratinocytes. GSK3787 (1 μM) largely antagonizes 50 nM GW0742-induced Angptl4 and Adrp mRNAs expression in skin cancer cell A341. GSK3787 (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). GSK3787 (1 μM) largely antagonizes GW0742-induced increase of Adrp mRNA in Huh7 and HepG2 cells but not in H1838 cells. GSK3787 does not antagonize basal expression of either of these two PPARβ/δtarget genes in these cells. Neither GW0742 nor GSK3787 has any effect on cell proliferation of these cells at concentrations ranging from 0.1 to 10 μM. GSK3787 is able to modulate the association of both PPARβ/δ and PPARγ coregulator peptides in response to ligand activation. Efficacy of GSK3787 to modulate PPARγ activity is markedly lower than the efficacy of GSK3787 to act as a PPARβ/δ antagonist. ^[2]
in vivo	GSK3787 antagonizes ligand-induced PPARβ/δ-dependent gene expression in vivo. Oral administration of GSK3787 has no effect on the expression of Angptl4 and Adrp mRNA in mouse colon epithelium. Coadministration of GSK3787 (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 GSK3787 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. GSK 3787 completely antagonizes the activity of agonist GW501516 with a pIC50 of 6.9 and 94% maximal inhibition. GSK3787 (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. GSK 3787 shows no effective antiproliferative activity against colorectal cancer cells. ^[1]

GSK3787 (1 μM) completely antagonizes 50 nM GW0742-induced PPARβ/δ-dependent Angptl4 gene expression in wild-type fibroblasts and in keratinocytes. GSK3787 (1 μM) largely antagonizes 50 nM GW0742-induced Angptl4 and Adrp mRNAs expression in skin cancer cell A341. GSK3787 (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). GSK3787 (1 μM) largely antagonizes GW0742-induced increase of Adrp mRNA in Huh7 and HepG2 cells but not in H1838 cells. GSK3787 does not antagonize basal expression of either of these two PPARβ/δtarget genes in these cells. Neither GW0742 nor GSK3787 has any effect on cell proliferation of these cells at concentrations ranging from 0.1 to 10 μM. GSK3787 is able to modulate the association of both PPARβ/δ and PPARγ coregulator peptides in response to ligand activation. Efficacy of GSK3787 to modulate PPARγ activity is markedly lower than the efficacy of GSK3787 to act as a PPARβ/δ antagonist. ^[2]

in vivo

GSK3787 antagonizes ligand-induced PPARβ/δ-dependent gene expression in vivo. Oral administration of GSK3787 has no effect on the expression of Angptl4 and Adrp mRNA in mouse colon epithelium. Coadministration of GSK3787 (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 GSK3787 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 [³H]GW3738 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 [³H]GW3738 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

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. ]

Selleckの高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：

PPARδ inhibition blocks the induction and function of tumor-induced IL-10+ regulatory B cells and enhances cancer immunotherapy [ Cell Discov, 2023, 9(1):54]	PubMed: 37291146
PPARδ inhibition blocks the induction and function of tumor-induced IL-10+ regulatory B cells and enhances cancer immunotherapy [ Cell Discov, 2023, 9(1):54]	PubMed: 37291146
PPAR-δ as a prognostic biomarker and its association with immune infiltrates in breast cancer PPAR-δ as a prognostic biomarker and its association with immune infiltrates in breast cancer [ J Cancer, 2023, 14(6):1049-1061]	PubMed: 37151397
Tumor-derived Lysophosphatidic Acid Blunts Protective Type-I Interferon Responses in Ovarian Cancer [ Cancer Discov, 2022, candisc.1181.2021]	PubMed: 35552618
Telmisartan is the most effective ARB to increase adiponectin via PPARα in adipocyte [ J Mol Endocrinol, 2022, JME-21-0239]	PubMed: 35354667
Mesenchymal stem cells alleviate experimental immune-mediated liver injury via chitinase 3-like protein 1-mediated T cell suppression [ Cell Death Dis, 2021, 12(3):240]	PubMed: 33664231
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
Meningitic Escherichia coli Induction of ANGPTL4 in Brain Microvascular Endothelial Cells Contributes to Blood-Brain Barrier Disruption via ARHGAP5/RhoA/MYL5 Signaling Cascade [ Pathogens, 2019, 8(4)E254]	PubMed: 31766605
Antagonism of PPAR-γ signaling expands human hematopoietic stem and progenitor cells by enhancing glycolysis. [ Nat Med, 2018, 24(3):360-367]	PubMed: 29377004

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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