Crenolanib

別名：CP-868596, ARO 002

製品コード：S2730 純度：99.99%

Crenolanib is a potent and selective inhibitor of PDGFRα/β with K_d of 2.1 nM/3.2 nM in CHO cells, also potently inhibits FLT3, sensitive to D842V mutation not V561D mutation, >100-fold more selective for PDGFR than c-Kit, VEGFR-2, TIE-2, FGFR-2, EGFR, erbB2, and Src. Crenolanib helps to induce mitophagy.

CAS No. 670220-88-9

サイズ	価格(税別)	在庫状況
10mM (1mL in DMSO)	JPY 40500	国内在庫あり
5mg	JPY 25500	国内在庫あり
50mg	JPY 145500	国内在庫あり
1g	JPY 598500	国内在庫なし(納期7~10日)

代表番号: 045-509-1970\|電子メール：[email protected] よく尋ねられる質問

文献中Selleckの製品使用例（95）

製品安全説明書

現在のバッチを見る：純度： 99.99%

99.99

Crenolanib関連製品

関連ターゲット	PDGFRα PDGFRβ	もっと見る
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関連化合物ライブラリー	Kinase Inhibitor Library Tyrosine Kinase Inhibitor Library PI3K/Akt Inhibitor Library Cell Cycle compound library Angiogenesis Related compound Library	もっと見る

シグナル伝達経路

PDGFRシグナル伝達経路

PDGFR阻害剤の選択性比較

Cell Data

Cell Lines	Assay Type	Concentration	Incubation Time	活性情報	PMID
A549 cells	Cell viability assay	3.9-1000 nM	72 h	a dose-dependent inhibition of cancer cell viability	25328409
MV4-11	Cytotoxicity assay	0.5 to 5000 nM	2 to 8 hrs	Cytotoxicity in human MV4-11 cells assessed as inhibition of cellular viability at 0.5 to 5000 nM incubated for 2 to 8 hrs followed by compound washout by CellTiter-Glo luminescent assay	30742435
MV4-11	Cytotoxicity assay		72 hrs	Cytotoxicity in human MV4-11 cells assessed as inhibition of cellular viability incubated for 72 hrs by CellTiter-Blue assay, IC50=0.012μM	30742435
MV4-11	Function assay			a decrease in mitochondrial matrix protein aconitase hydratase 2 (ACO2)	25328409
MV4-11	Cytotoxicity assay			Cytotoxicity against human MV4-11 cells expressing FLT3 ITD mutant, IC50=0.0015μM	31207462
MOLM13	Cytotoxicity assay			Cytotoxicity against human MOLM13 cells expressing FLT3 ITD mutant, IC50=0.0049μM	31207462
DAOY	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for DAOY cells	29435139
SJ-GBM2	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SJ-GBM2 cells	29435139
SK-N-MC	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SK-N-MC cells	29435139
BT-37	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for BT-37 cells	29435139
NB-EBc1	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for NB-EBc1 cells	29435139
U-2 OS	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for U-2 OS cells	29435139
Saos-2	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Saos-2 cells	29435139
LAN-5	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for LAN-5 cells	29435139
BT-12	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for BT-12 cells	29435139
Rh18	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh18 cells	29435139
OHS-50	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for OHS-50 cells	29435139
RD	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for RD cells	29435139
A673	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for A673 cells)	29435139
DAOY	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for DAOY cells	29435139
U-2 OS	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for U-2 OS cells	29435139
Rh41	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for Rh41 cells	29435139
SK-N-SH	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for SK-N-SH cells	29435139
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生物活性

製品説明

Targets

FLT3 ^[1] (CHO cells)	PDGFRα ^[1] (CHO cells)	PDGFRβ ^[1] (CHO cells)
0.74 nM(Kd)	2.1 nM(Kd)	3.2 nM(Kd)

In Vitro
In vitro	Crenolanib is significantly more potent in inhibiting the kinase activity of resistant PDGFRα kinases (D842I, D842V, D842Y, D1842-843IM, and deletion I843). Crenolanib is more potent against D842V in the isogenic model system, with an IC50 of approximately 10 nM. Crenolanib 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. Crenolanib also inhibits the proliferation of EOL-1 cells with IC50 = 0.2 pM. Crenolanib inhibits the activation of V561D or D842V-mutant kinases expressed in BaF3 cells with IC50 with 85 nM or 272 nM, respectively. Crenolanib 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. ^[1] Crenolanib is an orally bioavailable, highly potent and selective PDGFR TKI. Crenolanib is a benzimidazole compound that has IC50s of 0.9 nM and 1.8 nM for PDGFRA and PDGFRB, respectively. ^[2]
Kinase Assay	Biochemical Assessment of PDGFRα Kinase Activity
Kinase Assay	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 Crenolanib for a given mutation.
細胞実験	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.
実験結果図	Methods	Biomarkers	結果図	PMID
	Western blot	pAKT / AKT / pMAPK / MAPK / pSTAT5 / STAT5 pFLT3 / FLT3 / pERK / ERK / pS6 / S6 pKIT / KIT		24227820
	Growth inhibition assay	Cell viability		24623852

In Vivo
In Vivo	Crenolanib, a PDGFR inhibitor, suppresses lung cancer cell proliferation and inhibits tumor growth in vivo

NCT Number	Recruitment	Conditions	Sponsor/Collaborators	Start Date	Phases
臨床試験 (data from https://clinicaltrials.gov, updated on 2024-05-22)
NCT00949624	Completed	Advanced Solid Tumors	Arog Pharmaceuticals Inc.	December 2005	Phase 1

参考
[1] Heinrich MC, et al, Clin Cancer Res, 2012, Jun 27. [2] Heinrich M, et al, AACR, 2011, Abstract 3586. [3] Wang P, et al. Onco Targets Ther. 2014 Sep 26;7:1761-8.

参考

化学情報

分子量	443.54	化学式	C₂₆H₂₉N₅O₂
CAS No.	670220-88-9	SDF	Download Crenolanib SDFをダウンロードする
Smiles	CC1(COC1)COC2=CC3=C(C=C2)N(C=N3)C4=NC5=C(C=CC=C5N6CCC(CC6)N)C=C4
保管	3年-20°C粉	溶液の保管冷凍と解凍の繰り返しを避けるため小分けにしてください	1年-80°Cin solvent
保管	3年-20°C粉	溶液の保管冷凍と解凍の繰り返しを避けるため小分けにしてください	１ケ月-20°Cin solvent

In vitro
Batch:

DMSO : 88 mg/mL ( (198.4 mM)；吸湿したDMSOは溶解度を減少させます。新しいDMSOをご使用ください。)

Ethanol : 88 mg/mL

Water : Insoluble

モル濃度計算器

in vivo
Batch:

Add solvents to the product individually and in order.

投与溶液組成計算機

実験計算

モル濃度計算器

質量	濃度	体積	分子量
=	×	×

希釈計算器分子量計算器

投与溶液組成計算機(クリア溶液)

ステップ１：実験データを入力してください。（実験操作によるロスを考慮し、動物数を1匹分多くして計算・調製することを推奨します）

投与量 mg/kg 動物平均体重 g 投与体積（動物毎）μL 動物数匹

ステップ２：投与溶媒の組成を入力してください。（ロット毎に適した溶解組成が異なる場合があります。詳細については弊社までお問い合わせください）

% DMSO + % + % Tween 80 + % ddH₂O

%DMSO+ %

計算結果：

投与溶媒濃度： mg/ml;

DMSOストック溶液調製方法： mg 試薬を μL DMSOに溶解する（濃度 mg/mL, 注：濃度が当該ロットのDMSO溶解度を超える場合はご連絡ください。 )

投与溶媒調製方法：Take μL DMSOストック溶液に μL PEG300，を加え、完全溶解後μL Tween 80，を加えて完全溶解させた後 μL ddH₂O，を加え完全に溶解させます。

投与溶媒調製方法：μL DMSOストック溶液に μL Corn oil，を加え、完全溶解。

注意：１.ストック溶液に沈殿、混濁などがないことをご確認ください；
２.順番通りに溶剤を加えてください。次のステップに進む前に溶液に沈殿、混濁などがないことを確認してから加えてください。ボルテックス、ソニケーション、水浴加熱など物理的な方法で溶解を早めることは可能です。

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