Crenolanib (CP-868596)

製品コードS2730 バッチS273005

化学情報

	Synonyms	CP-868596, ARO 002	Storage (From the date of receipt)	3 years -20°C powder 1 years -80°C in solvent
	化学式	C₂₆H₂₉N₅O₂
	分子量	443.54	CAS No.	670220-88-9
Solubility (25°C)*	体外	DMSO	88 mg/mL (198.4 mM)
		Ethanol	88 mg/mL (198.4 mM)
		Water	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	Crenolanibは、CHO細胞において2.1nM/3.2nMのK_dを持つPDGFRα/βの強力かつ選択的な阻害剤であり、FLT3も強力に阻害します。D842V変異には感受性を示しますが、V561D変異には示しません。c-Kit、VEGFR-2、TIE-2、FGFR-2、EGFR、erbB2、およびSrcよりもPDGFRに対して100倍以上選択的です。Crenolanibはmitophagyの誘導を助けます。
in vitro	Crenolanib is significantly more potent in inhibiting the kinase activity of resistant PDGFRα kinases (D842I, D842V, D842Y, D1842-843IM, and deletion I843). This compound is more potent against D842V in the isogenic model system, with an IC50 of approximately 10 nM. It inhibits the kinase activity of the fusion oncogene in EOL-1 cell line, which is derived from a patient with chronic eosinophilic leukemia and expresses the constitutively activated FIP1L1- PDGFRα fusion kinase, with IC50 = 21 nM. This chemical also inhibits the proliferation of EOL-1 cells with IC50 = 0.2 pM. It inhibits the activation of V561D or D842V-mutant kinases expressed in BaF3 cells with IC50 with 85 nM or 272 nM, respectively. This compound inhibits PDGFRα activation in H1703 non-small cell lung cancer cell line which has 24-fold amplification of the 4q12 region that contains the PDGFRα locus, with IC50 with 26 nM. It is an orally bioavailable, highly potent and selective PDGFR TKI. This benzimidazole compound has IC50s of 0.9 nM and 1.8 nM for PDGFRA and PDGFRB, respectively.
in vivo	This compound, a PDGFR inhibitor, suppresses lung cancer cell proliferation and inhibits tumor growth in vivo

製品説明

Crenolanibは、CHO細胞において2.1nM/3.2nMのK_dを持つPDGFRα/βの強力かつ選択的な阻害剤であり、FLT3も強力に阻害します。D842V変異には感受性を示しますが、V561D変異には示しません。c-Kit、VEGFR-2、TIE-2、FGFR-2、EGFR、erbB2、およびSrcよりもPDGFRに対して100倍以上選択的です。Crenolanibはmitophagyの誘導を助けます。

in vitro

Crenolanib is significantly more potent in inhibiting the kinase activity of resistant PDGFRα kinases (D842I, D842V, D842Y, D1842-843IM, and deletion I843). This compound is more potent against D842V in the isogenic model system, with an IC50 of approximately 10 nM. It inhibits the kinase activity of the fusion oncogene in EOL-1 cell line, which is derived from a patient with chronic eosinophilic leukemia and expresses the constitutively activated FIP1L1- PDGFRα fusion kinase, with IC50 = 21 nM. This chemical also inhibits the proliferation of EOL-1 cells with IC50 = 0.2 pM. It inhibits the activation of V561D or D842V-mutant kinases expressed in BaF3 cells with IC50 with 85 nM or 272 nM, respectively. This compound inhibits PDGFRα activation in H1703 non-small cell lung cancer cell line which has 24-fold amplification of the 4q12 region that contains the PDGFRα locus, with IC50 with 26 nM.

It is an orally bioavailable, highly potent and selective PDGFR TKI. This benzimidazole compound has IC50s of 0.9 nM and 1.8 nM for PDGFRA and PDGFRB, respectively.

in vivo

This compound, a PDGFR inhibitor, suppresses lung cancer cell proliferation and inhibits tumor growth in vivo

プロトコル(参考用のみ)

キナーゼアッセイ	Biochemical Assessment of PDGFRα Kinase Activity
キナーゼアッセイ	Chinese hamster ovary (CHO) cells are transiently transfected with mutated or wild type PDGFRα constructs and treated with various concentrations of Crenolanib. Experiments involving recombinant DNA are performed using biosafety level 2 conditions in accordance with guidelines. Protein lysates from cell lines are prepared and subjected to immunoprecipitation using anti-PDGFRα antibodies followed by sequential immunoblotting for PDGFRα. Densitometry is performed to quantify drug effect using Photoshop software, with the level of phosphor- PDGFRα normalized to total protein. Densitometry and proliferation experimental results are analyzed using Calcusyn 2.1 software to mathematically determine the IC50 values. The Wilcoxon Rank Sum Test is used to compare the IC50 values of this compound for a given mutation.
細胞アッセイ	細胞株	EOL-1 cell line
	濃度	0-20 pM
	反応時間	72 hours
	実験の流れ	Cells are added to 96-well plates at densities of 20, 000 cells/well and incubated with Crenolanib for 72 hours before measuring cellular proliferation using a 2,3-bis[2-methoxyl-4-nitro-5-sulfophenyl]-2H-tetrazolium-5-carboxanilide (XTT)-based assay.
動物実験	動物モデル	Xenograft mice
	投薬量	10 or 20 mg/kg
	投与方法

参考

https://pubmed.ncbi.nlm.nih.gov/22745105/
http://www.abstractsonline.com/Plan/ViewAbstract.aspx?sKey=37bcae41-860c-44f3-a18f-fe31ecc9581f&cKey
https://pubmed.ncbi.nlm.nih.gov/25328409/

カスタマーフィードバック

: Data from [Data independently produced by Proc Natl Acad Sci U S A, 2014, 111(14), 5319-24]

: Data from [Data independently produced by Mol Cancer, 2014, 13(1), 247]

: Data from [Data independently produced by Onco Targets Ther, 2014, 7, 1761-8]

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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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