Dubermatinib(TP-0903)

製品コード：S7846 純度：99.95%

TP-0903 is a potent and selective AXL Inhibitor with IC50 of 27 nM. TP-0903 is highly effective in inducing apoptosis.

CAS No. 1341200-45-0

サイズ	価格(税別)	在庫状況
5mg	JPY 26400	国内在庫あり
25mg	JPY 84500	国内在庫あり

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

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カスタマーフィードバック3个实验数据

製品安全説明書

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99.95

Dubermatinib(TP-0903)関連製品

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

Axl阻害剤の選択性比較

生物活性

製品説明

TP-0903 is a potent and selective AXL Inhibitor with IC50 of 27 nM. TP-0903 is highly effective in inducing apoptosis.

Targets

Axl ^[1]
(Cell-free assay)

27 nM

In Vitro
In vitro	In pancreatic cancer cells (PSN-1), TP-0903 shows strong antiproliferative activity with IC50 of 6 M. TP-0903 also induces strong G2/M arrest by potently inhibiting Aurora A and B. [1] In CLL B cells from all the patients with CLL, TP-0903 causes a dose-dependent induction of massive apoptosis by targeting phosphorylated Axl, and overcomes CLL BMSC-mediated protection of CLL B cells from apoptosis. ^[2]
Kinase Assay	Axl Kinase activity assay
Kinase Assay	Test compounds are diluted to desired concentrations in kinase reaction buffer (50 mM HEPES pH 7.5, 10 mM MgCl², 1 mM EGTA, 2 mM DTT, and 0.01% v/v Tween-20) and are briefly incubated with Axl kinase. The Axl kinase used is recombinant human Axl kinase (catalytic domain, amino acids 473-894) with a histidine tag. The reaction is initiated by the addition of ATP and fluorescein-labeled poly-GT substrate (poly Glu:Tyr, 4:1 polymer). Concentration of the various components in the assay (10 µL reaction volume) are: 1% DMSO, 93 ng/mL Axl kinase, 20 µM ATP, and 200 nM fluorescein poly-GT substrate. Following addition of ATP and fluorescein poly-GT substrate, incubation is for 60 min at room temperature, the enzyme reaction is stopped by addition of 10 µL terbium-labeled anti-phosphotyrosine PY20 antibody in EDTA-containing buffer. Final concentration of EDTA and antibody after addition to the reaction is 10 mM and 2 nM, respectively. The terbium conjugated antibody generates a time-resolved FRET signal with the fluorescein molecule (bound to the poly-GT substrate) when the substrate is phosphorylated. After one hour incubation at room temperature, fluorescence is measured with excitation of 320 nm and dual emission of 495 and 520 nm on an EnVision microplate reader. Signal is expressed in -636996terms of a TR-FRET ratio (fluorescence intensity at 520 nm to 495 nm).
細胞実験	細胞株	PSN-1 cells
	濃度	--
	反応時間	96 hours
	実験の流れ	For cell proliferation assays, 45 µL containing 1000 cells per well are seeded into solid white 384-well plates in appropriate cell growth media containing 10% FBS and incubated overnight at 37 °C and 5% CO₂. The following day, test compounds are diluted in serum free growth media to 10x desired concentrations and 5 µL is added to each well. Combined compound and cells are incubated for 96 hours. Following incubation, 40 µL of ATP-Lite solution is added to each well, incubated for an additional 10 minutes at room temperature and luminescence is measured on an EnVision microplate reader. Percent cell viability for test compounds is calculated by comparing treated wells to appropriate controls (e.g. vehicle treated) included on each plate.
実験結果図	Methods	Biomarkers	結果図	PMID
実験結果図	Western blot	p-AKT / AKT / p-SFK / Lyn / Bcl-2 / XIAP / Mcl-1		25673699

In Vivo
In Vivo	In the adult rat hippocampus, the intracerebroventricular administration of SAG (2.5 nM) significantly increases the number of newly generated cells and extends survival of hippocampal cells. ^[3] In mice, SAG (20 μg/g, i.p.) effectively prevents GC-induced neonatal cerebellar developmental abnormalities. ^[4]

NCT Number	Recruitment	Conditions	Sponsor/Collaborators	Start Date	Phases
臨床試験 (data from https://clinicaltrials.gov, updated on 2024-01-11)
NCT04518345	Completed	Acute Myeloid Leukemia\|Secondary Acute Myeloid Leukemia\|Therapy-Related Acute Myeloid Leukemia	Uma Borate\|Sumitomo Pharma America Inc.\|Ohio State University Comprehensive Cancer Center	November 5 2020	Early Phase 1
NCT02729298	Completed	Advanced Solid Tumors\|EGFR Positive Non-small Cell Lung Cancer\|Colorectal Carcinoma\|Recurrent Ovarian Carcinoma\|BRAF-Mutated Melanoma	Sumitomo Pharma America Inc.	December 14 2016	Phase 1

参考
[1] Mollard A, et al. ACS Med Chem Lett. 2011, 2(12), 907-912. [2] Sinha S, et al. Clin Cancer Res. 2015, 21(9), 2115-2126.

参考

化学情報

分子量	516.06	化学式	C₂₄H₃₀ClN₇O₂S
CAS No.	1341200-45-0	SDF	Download Dubermatinib(TP-0903) SDFをダウンロードする
Smiles	CN1CCN(CC1)CC2=CC=C(C=C2)NC3=NC=C(C(=N3)NC4=CC=CC=C4S(=O)(=O)N(C)C)Cl
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个月-20°Cin solvent

In vitro
Batch:

DMSO : 3 mg/mL ( (5.81 mM)； Warmed with 50℃ water bath; 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 : 2 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。

技術サポート

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Handling Instructions

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* 必須

C1=C0/X	C1:	LOG(C1):
C2=C1/X	C2:	LOG(C2):
C3=C2/X	C3:	LOG(C3):
C4=C3/X	C4:	LOG(C4):
C5=C4/X	C5:	LOG(C5):
C6=C5/X	C6:	LOG(C6):
C7=C6/X	C7:	LOG(C7):
C8=C7/X	C8:	LOG(C8):