Entrectinib (Rxdx-101)

別名：RXDX-101, NMS-E628

製品コード：S7998 純度：99.93%

Entrectinib is an orally bioavailable pan-TrkA/B/C, ROS1 and ALK inhibitor with IC50 ranging between 0.1 and 1.7 nM. Entrectinib (RXDX-101) induces autophagy. Phase 2.

CAS No. 1108743-60-7

サイズ	価格(税別)	在庫状況
10mM (1mL in DMSO)	JPY 28500	国内在庫あり
5mg	JPY 22000	国内在庫あり
25mg	JPY 56500	国内在庫あり
100mg	JPY 127000	国内在庫あり
1g	JPY 220500	国内在庫なし(納期7~10日)

代表番号: 045-509-1970\|電子メール：sales@selleck.co.jp よく尋ねられる質問

文献中Selleckの製品使用例（59）

製品安全説明書

現在のバッチを見る：純度： 99.93%

99.93

Entrectinib (Rxdx-101)関連製品

関連ターゲット	TrkA TrkB TrkC	もっと見る
関連製品	ANA-12 GW441756 7,8-Dihydroxyflavone GNF-5837 Selitrectinib (LOXO-195) LM22B-10 Altiratinib BDNF Antibody [E17G19] N-Acetyl-5-hydroxytryptamine	もっと見る
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

Trk receptorシグナル伝達経路

Trk receptor阻害剤の選択性比較

Cell Data

Cell Lines	Assay Type	Concentration	Incubation Time	活性情報	PMID
KARPAS299	Function assay	60 mg/kg	12 hrs	Ex vivo inhibition of NPM-ALK phosphorylation in SCID mouse xenografted with human KARPAS299 cells at 60 mg/kg, po administered as single dose measured after 12 hrs by Western blot analysis	27003761
KARPAS299	Function assay	60 mg/kg	18 hrs	Ex vivo inhibition of NPM-ALK phosphorylation in SCID mouse xenografted with human KARPAS299 cells at 60 mg/kg, po administered as single dose measured after 18 hrs by Western blot analysis	27003761
KARPAS299	Function assay	60 mg/kg	12 hrs	Ex vivo inhibition of NPM-ALK phosphorylation in SCID mouse xenografted with human KARPAS299 cells assessed as suppression of STAT3 phosphorylation at 60 mg/kg, po administered as single dose measured after 12 hrs by Western blot analysis	27003761
KARPAS299	Function assay	60 mg/kg	18 hrs	In vivo inhibition of NPM-ALK phosphorylation in SCID mouse xenografted with human KARPAS299 cells assessed as suppression of STAT3 phosphorylation at 60 mg/kg, po administered as single dose measured after 18 hrs by Western blot analysis	27003761
NCI-H2228	Antitumor assay	30 to 60 mg/kg	10 days	Antitumor activity against human NCI-H2228 cells xenografted in athymic nu/nu mouse assessed as tumor growth inhibition at 30 to 60 mg/kg, po bid administered for 10 days	27003761
NCI-H2228	Function assay	60 mg/kg	12 hrs	Ex vivo inhibition of EML4-ALK phosphorylation in athymic nu/nu mouse xenografted with human NCI-H2228 cells at 60 mg/kg, po administered as single dose measured after 12 hrs by Western blot analysis	27003761
NCI-H2228	Function assay	60 mg/kg	18 hrs	Ex vivo inhibition of EML4-ALK phosphorylation in athymic nu/nu mouse xenografted with human NCI-H2228 cells at 60 mg/kg, po administered as single dose measured after 18 hrs by Western blot analysis	27003761
NCI-H2228	Function assay	60 mg/kg	12 hrs	Ex vivo inhibition of EML4-ALK phosphorylation in athymic nu/nu mouse xenografted with human NCI-H2228 cells assessed as suppression of AKT phosphorylation at 60 mg/kg, po administered as single dose measured after 12 hrs by Western blot analysis	27003761
NCI-H2228	Function assay	60 mg/kg	18 hrs	Ex vivo inhibition of EML4-ALK phosphorylation in athymic nu/nu mouse xenografted with human NCI-H2228 cells assessed as suppression of AKT phosphorylation at 60 mg/kg, po administered as single dose measured after 18 hrs by Western blot analysis	27003761
KARPAS299	Antitumor assay	30 to 60 mg/kg	10 days	Antitumor activity against human KARPAS299 cells xenografted in SCID mouse assessed as tumor growth inhibition at 30 to 60 mg/kg, po bid administered for 10 days	27003761
KARPAS299	Antitumor assay	30 to 60 mg/kg	10 days	Antitumor activity against human KARPAS299 cells xenografted in SCID mouse assessed as tumor free cured mouse at 30 to 60 mg/kg, po bid administered for 10 days measured on day 90	27003761
BAF3	Function assay		72 hrs	Inhibition of human TEL (336 residues) fused-ROS1 (1891 to 2347 residues) (unknown origin) expressed in mouse BAF3 cells assessed as cell growth inhibition after 72 hrs by cell titer-glo assay, IC50 = 0.005 μM.	27003761
BAF3	Function assay		72 hrs	Inhibition of human TEL (336 residues) fused-TRKC (454 to 825 residues) (unknown origin) expressed in mouse BAF3 cells assessed as cell growth inhibition after 72 hrs by cell titer-glo assay, IC50 = 0.003 μM.	27003761
BAF3	Function assay		72 hrs	Inhibition of human TEL (336 residues) fused-TRKA (440 to 796 residues) (unknown origin) expressed in mouse BAF3 cells assessed as cell growth inhibition after 72 hrs by cell titer-glo assay, IC50 = 0.003 μM.	27003761
BAF3	Function assay		72 hrs	Inhibition of human TEL (336 residues) fused-TRKB (455 to 822 residues) (unknown origin) expressed in mouse BAF3 cells assessed as cell growth inhibition after 72 hrs by cell titer-glo assay, IC50 = 0.003 μM.	27003761
KM12	Antiproliferative assay		72 hrs	Antiproliferative activity against human KM12 cells expressing TRKA protein incubated for 72 hrs by cell titer-glo assay, IC50 = 0.017 μM.	27003761
SU-DHL1	Antiproliferative assay		72 hrs	Antiproliferative activity against human SU-DHL1 cells expressing ALK protein incubated for 72 hrs by cell titer-glo assay, IC50 = 0.024 μM.	27003761
BAF3	Function assay		72 hrs	Inhibition of wild type EML4-ALK (unknown origin) expressed in mouse BAF3 cells assessed as cell growth inhibition after 72 hrs by cell titer-glo assay, IC50 = 0.028 μM.	27003761
KARPAS299	Antiproliferative assay		72 hrs	Antiproliferative activity against human KARPAS299 cells incubated for 72 hrs by cell titer-glo assay, IC50 = 0.031 μM.	27003761
SUP-M2	Antiproliferative assay		72 hrs	Antiproliferative activity against human SUP-M2 cells expressing ALK protein incubated for 72 hrs by cell titer-glo assay, IC50 = 0.041 μM.	27003761
BAF3	Function assay		72 hrs	Inhibition of EML4-ALK L1196M mutant (unknown origin) expressed in mouse BAF3 cells assessed as cell growth inhibition after 72 hrs by cell titer-glo assay, IC50 = 0.067 μM.	27003761
NCI-H2228	Antiproliferative assay		72 hrs	Antiproliferative activity against human NCI-H2228 cells expressing ALK protein incubated for 72 hrs by cell titer-glo assay, IC50 = 0.068 μM.	27003761
MV411	Antiproliferative assay		72 hrs	Antiproliferative activity against human MV411 cells incubated for 72 hrs by cell titer-glo assay, IC50 = 0.081 μM.	27003761
SR786	Antiproliferative assay		72 hrs	Antiproliferative activity against human SR786 cells expressing ALK protein incubated for 72 hrs by cell titer-glo assay, IC50 = 0.081 μM.	27003761
BAF3	Function assay		72 hrs	Inhibition of EML4-ALK G1202R mutant (unknown origin) expressed in mouse BAF3 cells assessed as cell growth inhibition after 72 hrs by cell titer-glo assay, IC50 = 0.897 μM.	27003761
BA/F3	Cytotoxicity assay		72 hrs	Cytotoxicity against mouse IL-3 dependent BA/F3 cells incubated for 72 hrs by cell titer-glo assay, IC50 = 2.104 μM.	27003761
KM12	Function assay		2 hrs	Inhibition of TPM3-TRKA phosphorylation in human KM12 cells at low concentration after 2 hrs by Western blot analysis	27003761
KM12	Function assay		2 hrs	Inhibition of TPM3-TRKA phosphorylation in human KM12 cells assessed as suppression of MAPK phosphorylation at low concentration after 2 hrs by Western blot analysis	27003761
KM12	Function assay		2 hrs	Inhibition of TPM3-TRKA phosphorylation in human KM12 cells assessed as suppression of PLCgamma1 phosphorylation at low concentration after 2 hrs by Western blot analysis	27003761
KM12	Function assay		2 hrs	Inhibition of TPM3-TRKA phosphorylation in human KM12 cells assessed as suppression of AKT phosphorylation at low concentration after 2 hrs by Western blot analysis	27003761
KM12	Function assay		2 hrs	Inhibition of TPM3-TRKA phosphorylation in human KM12 cells assessed as suppression of S6 phosphorylation at low concentration after 2 hrs by Western blot analysis	27003761
KARPAS299	Function assay		2 hrs	Inhibition of NPM/ALK autophosphorylation in human KARPAS299 cells at very low concentration after 2 hrs by Western blot analysis	27003761
NCI-H2228	Function assay		2 hrs	Inhibition of NPM/ALK autophosphorylation in human NCI-H2228 cells at very low concentration after 2 hrs by Western blot analysis	27003761
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生物活性

製品説明

Entrectinib is an orally bioavailable pan-TrkA/B/C, ROS1 and ALK inhibitor with IC50 ranging between 0.1 and 1.7 nM. Entrectinib (RXDX-101) induces autophagy. Phase 2.

Targets

TrkA

TrkB

TrkC

ROS1

ALK

In Vitro
In vitro	Entrectinib selectively blocks proliferation of ALK-dependent cell lines and potently inhibits ALK‐dependent signaling. This compound also highly inhibits cell growth of the NSCLC cell line NCI‐H2228 bearing the EML4-ALK rearrangement.
実験結果図	Methods	Biomarkers	結果図	PMID
	Western blot	pAKT / AKT pTrkA-Y490 / TrkA / p-PLCγ-Y783 / PLCγ p-ALK / ALK / p-ERK / ERK / p-STAT3 / STAT3 Cyclin A1 / Cyclin E1 / p27 / p21		26172300
	Growth inhibition assay	Cell viability		26172300

In Vivo
In Vivo	In mice bearing Karpas-299 and SR-786 xenografts, Entrectinib (p.o.) induces complete tumor regression. In NPM-ALK transgenic mice, this compound induces complete regression of tumor masses observed in the thymus and in lymph nodes. In the NB xenograft model, this compound cotreatment enhanced the efficacy of conventional chemotherapy.

In Vivo

In mice bearing Karpas-299 and SR-786 xenografts, Entrectinib (p.o.) induces complete tumor regression. In NPM-ALK transgenic mice, this compound induces complete regression of tumor masses observed in the thymus and in lymph nodes.

In the NB xenograft model, this compound cotreatment enhanced the efficacy of conventional chemotherapy.

NCT Number	Recruitment	Conditions	Sponsor/Collaborators	Start Date	Phases
臨床試験 (data from https://clinicaltrials.gov, updated on 2024-05-22)
NCT05770544	Recruiting	Solid Tumor\|Haematological Malignancy\|Malignancy\|Malignant Neoplasm\|Lymphoproliferative Disorders\|Neoplasms by Histologic Type\|Neoplasms by Site\|Cancer\|Brain Neoplasms\|Melanoma\|Glioma	Cancer Research UK\|University of Manchester\|University of Birmingham\|Royal Marsden NHS Foundation Trust\|Hoffmann-La Roche	June 2024	Phase 2\|Phase 3
NCT04551495	Recruiting	Invasive Lobular Breast Carcinoma\|ER+ Breast Cancer\|HER2-negative Breast Cancer	Jules Bordet Institute\|Hoffmann-La Roche	January 14 2021	Phase 2
NCT04226833	Completed	Hepatic Insufficiency	Hoffmann-La Roche	February 11 2020	Phase 1
NCT03796013	Completed	Healthy Volunteers	Genentech Inc.	January 10 2019	Phase 1

参考
https://pubmed.ncbi.nlm.nih.gov/26457764/ http://mct.aacrjournals.org/content/8/12_Supplement/A244.short http://cancerres.aacrjournals.org/content/75/15_Supplement/5390 https://pubmed.ncbi.nlm.nih.gov/36101520/ https://pubmed.ncbi.nlm.nih.gov/33229458/ + 展開

参考

https://pubmed.ncbi.nlm.nih.gov/26457764/
http://mct.aacrjournals.org/content/8/12_Supplement/A244.short
http://cancerres.aacrjournals.org/content/75/15_Supplement/5390

https://pubmed.ncbi.nlm.nih.gov/36101520/
https://pubmed.ncbi.nlm.nih.gov/33229458/

+ 展開

化学情報

分子量	560.64	化学式	C₃₁H₃₄F₂N₆O₂
CAS No.	1108743-60-7	SDF	Download Entrectinib (Rxdx-101) SDFをダウンロードする
Smiles	CN1CCN(CC1)C2=CC(=C(C=C2)C(=O)NC3=NNC4=C3C=C(C=C4)CC5=CC(=CC(=C5)F)F)NC6CCOCC6
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 : 100 mg/mL ( (178.36 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 : 100 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
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.
Clear solution	5%DMSO 1 40%PEG300 2 5%Tween80 3 50%ddH2O この製剤はselleckのラボで検証済みです。上記の溶解方法がご要望を満たさない場合、selleckの営業担当までお問い合わせ頂ければ、個別の試験を行います。	5.000mg/ml (8.92mM)	Taking the 1 mL working solution as an example, add 50 μL of 100 mg/ml clarified DMSO stock solution to 400 μL of PEG300, mix evenly to clarify it; add 50 μL of Tween80 to the above system, mix evenly to make it clear; then continue to add 500 μL of ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results.
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.
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.

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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