Dorsomorphin 2HCl

製品コードS7306 バッチS730605

化学情報

	Synonyms	BML-275 2HCl,Compound C 2HCl	Storage (From the date of receipt)	3 years -20°C powder 1 years -80°C in solvent
	化学式	C₂₄H₂₅N₅O.2HCl
	分子量	472.41	CAS No.	1219168-18-9
Solubility (25°C)*	体外	Water	94 mg/mL (198.97 mM)
		DMSO	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	Dorsomorphin 2HCl is a potent, reversible, selective AMPK inhibitor with K_i of 109 nM in cell-free assays, exhibiting no significant inhibition of several structurally related kinases including ZAPK, SYK, PKCθ, PKA, and JAK3. Also inhibits type Ⅰ BMP receptor activity. Dorsomorphin induces autophagy in cancer cell line.
in vitro	Dorsomorphin inhibits ACC inactivation by either AICAR or metformin, and also attenuates AICAR and metformin’s effect to increase fatty acid oxidation or suppress lipogenic genes in hepatocytes. ^[1] Inhibition of AMPK activity by Dorsomorphin almost completely inhibits autophagic proteolysis in HT-29 cells. ^[2] In addition, Dorsomorphin selectively inhibits the BMP type I receptors ALK2, ALK3 and ALK6, and thus blocks BMP-mediated SMAD1/5/8 phosphorylation, target gene transcription and osteogenic differentiation. ^[3]
in vivo	Dorsomorphin (10 mg/kg) reduces basal levels of hepcidin expression and increases serum iron concentrations in adult mice. ^[3] Dorsomorphin (0.2 mg/kg, i.v.) significantly reduces VCAM-1 and ICAM-1 expression in the thoracic aorta of LPS-treated rats. ^[4]

製品説明

Dorsomorphin 2HCl is a potent, reversible, selective AMPK inhibitor with K_i of 109 nM in cell-free assays, exhibiting no significant inhibition of several structurally related kinases including ZAPK, SYK, PKCθ, PKA, and JAK3. Also inhibits type Ⅰ BMP receptor activity. Dorsomorphin induces autophagy in cancer cell line.

in vitro

Dorsomorphin inhibits ACC inactivation by either AICAR or metformin, and also attenuates AICAR and metformin’s effect to increase fatty acid oxidation or suppress lipogenic genes in hepatocytes. ^[1]

Inhibition of AMPK activity by Dorsomorphin almost completely inhibits autophagic proteolysis in HT-29 cells. ^[2]

In addition, Dorsomorphin selectively inhibits the BMP type I receptors ALK2, ALK3 and ALK6, and thus blocks BMP-mediated SMAD1/5/8 phosphorylation, target gene transcription and osteogenic differentiation. ^[3]

in vivo

Dorsomorphin (10 mg/kg) reduces basal levels of hepcidin expression and increases serum iron concentrations in adult mice. ^[3]

Dorsomorphin (0.2 mg/kg, i.v.) significantly reduces VCAM-1 and ICAM-1 expression in the thoracic aorta of LPS-treated rats. ^[4]

プロトコル(参考用のみ)

キナーゼアッセイ	AMPK partial purification and in vitro kinase assay.
キナーゼアッセイ	Liver AMPK is partially purified from male SD rats to the blue-Sepharose step. The 100-μl reaction mixture contains 100 μM AMP, 100 μM ATP (0.5 μCi ³³P-ATP per reaction), and 50 μM SAMS in a buffer (40 mM HEPES, pH 7.0, 80 mM NaCl, 0.8 mM EDTA, 5 mM MgCl₂, 0.025% BSA, and 0.8 mM DTT). The reaction is initiated with addition of the enzyme. After 30-minute incubation at 30°C, the reaction is stopped by addition of 80 μl 1% H₃PO₄. Aliquots (100 μl) are transferred to 96-well MultiScreen plates. The plate is washed three times with 1% H3PO4 followed by detection in a Top-count. The in vitro AMPK inhibition data obtained with compound C — (6-[4-(2-Piperidin-1-yl-ethoxy)-phenyl)]-3-pyridin-4-yl-pyyrazolo[1,5-a] pyrimidine — are fit to the following equation for competitive inhibition by nonlinear regression using a least-squares Marquardt algorithm in a computer program written by N. Thornberry of Merck Research Laboratories: Vi/Vo = (K_m + S)/[S + K_m × (1 + I/K_i)], where Vi is the inhibited velocity, Vo is the initial velocity, S is the substrate (ATP) concentration, K_m is the Michaelis constant for ATP, I is the inhibitor (compound C) concentration, and K_i is the dissociation constant for compound C.
細胞アッセイ	細胞株	NIH3T3 cells
	濃度	10 μM
	反応時間	3 days
	実験の流れ	Cells were treated with hydrogen peroxide and incubated in complete medium with or without treatment with the AMPK activators metformin (10 μM), AICAR (10 μM), alone or plus AMPK inhibitor Compound C (CC, 10 μM) for 3 days.
動物実験	動物モデル	Iron-replete mice
	投薬量	~10 mg/kg
	投与方法	i.v.

参考

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カスタマーフィードバック

: , , Mol Brain, 2015 ,8:20.

: , , FEBS Lett, 2015, 589(15):1847-54.

: , , FEBS Letters, 2015, 1847-1854.

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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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