Rabusertib (LY2603618)

Rabusertib (LY2603618, IC-83) is a highly selective Chk1 inhibitor with potential anti-tumor activity in a cell-free assay. IC50=7 nM, showing approximately 100-fold more potent against Chk1 than against any of the other protein kinases evaluated. Rabusertib (LY2603618) induces cell cycle arrest, DNA damage response and autophagy in cancer cells. Rabusertib (LY2603618) induces bak-dependent apoptosis in AML cell lines.

CAS No. 911222-45-2

サイズ	価格(税別)	在庫状況
10mM (1mL in DMSO)	JPY 37000	国内在庫あり
5mg	JPY 25500	国内在庫あり
50mg	JPY 104500	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（85）

製品安全説明書

現在のバッチを見る：純度： 99.99%

99.99

Rabusertib (LY2603618)関連製品

関連ターゲット	Chk1 Chk2	もっと見る
関連製品	AZD7762 MK-8776 (SCH 900776) CHIR-124 Prexasertib HCl (LY2606368) PF-477736 BML-277 (Chk2 Inhibitor II) Prexasertib (LY2606368) CCT245737 (SRA737) GDC-0575	もっと見る
関連化合物ライブラリー	Kinase Inhibitor Library PI3K/Akt Inhibitor Library MAPK Inhibitor Library DNA Damage/DNA Repair compound Library Cell Cycle compound library	もっと見る

シグナル伝達経路

Chkシグナル伝達経路

Chk阻害剤の選択性比較

Cell Data

Cell Lines	Assay Type	Concentration	活性情報	PMID
A549	Function assay	~20 μM	activates DNA damage sensor kinases	24928205
H1299	Function assay	~10 μM	induces cell cycle arrest	24928205
A549	Function assay	~10 μM	induces cell cycle arrest	24928205
Calu6	Kinase assay	3300 nM	inhibits Chk1 activity	24114124
Hela	Kinase assay	3300 nM	inhibits Chk1 activity	24114124
MCF7	Kinase assay	1 μM	inhibits P-CHK1 levels	23917378
BT474	Kinase assay	1 μM	inhibits P-CHK1 levels	23917378
H1299	Function assay	~20 μM	activates DNA damage sensor kinases	24928205
A549	Apoptosis assay	~20 μM	induces apoptosis	24928205
H1299	Apoptosis assay	~20 μM	induces apoptosis	24928205
A549	Cytoxicity assay	~20 μM	induces autophagy	24928205
H1299	Cytoxicity assay	~20 μM	induces autophagy	24928205
A549	Function assay	~20 μM	increases JNK and p38 MAPK phosphorylation	24928205
H1299	Function assay	~20 μM	increases JNK and p38 MAPK phosphorylation	24928205
OHS-50	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for OHS-50 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
NB-EBc1	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for NB-EBc1 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
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生物活性

製品説明

Rabusertib (LY2603618, IC-83) is a highly selective Chk1 inhibitor with potential anti-tumor activity in a cell-free assay. IC50=7 nM, showing approximately 100-fold more potent against Chk1 than against any of the other protein kinases evaluated. Rabusertib (LY2603618) induces cell cycle arrest, DNA damage response and autophagy in cancer cells. Rabusertib (LY2603618) induces bak-dependent apoptosis in AML cell lines.

Targets

Chk1 ^[1]
(Cell-free assay)

7 nM

In Vitro
In vitro	Chk1 is an ATP-dependent serine-threonine kinase and a key component in the DNA replication-monitoring checkpoint system activated by double-stranded breaks (DSBs). Chk1 contributes to all currently defined cell cycle checkpoints, including G1/S, intra-S-phase, G2/M, and the mitotic spindle checkpoint. By inhibiting the activity of chk1, LY2603618 prevents the repair of DNA caused by DNA-damaging agents, thus potentiating the antitumor efficacies of various chemotherapeutic agents. However, preclinical data involving LY2603618 has not been published until now. ^[1] Inhibition of Chk1 is predicted to enhance the effects of antimetabolites, such as gemcitabine. ^[2] LY2603618 treatment impairs DNA synthesis, increases DNA damage (via mitotic defects), induces apoptosis, and has synergistic activity with pemetrexed, especially in p53 mutant tumor cells. ^[3]
細胞実験	細胞株	A549 and H1299 cell
	濃度	5 or 10 μM
	反応時間	24 h
	実験の流れ	Cells were treated with LY2603618 and DMSO as a control. After trypsinization, cells were fixed in 70 % ethanol at 4 C overnight. The cells were washed twice with PBS and incubated for 30 min in the dark in PBS containing propidium iodide (PI) and RNase A. Stained cells were analyzed by a FACScan flow cytometry and CellQuest analysis software.
実験結果図	Methods	Biomarkers	結果図	PMID
	Western blot	p-Chk1 / Chk1 / CDC25A PARP / CF-PARP / p-CDC25C / p-CDK1 / p-CDK2		29326282
	Growth inhibition assay	Cell viability		29326282

In Vivo
In Vivo	In xenograft models, LY2603618 delays tumor growth when given in combination with pemetrexed. ^[3]
動物実験	動物モデル	Male Wistar rats
	投与量	50 mg/kg
	投与経路	i.p.

NCT Number	Recruitment	Conditions	Sponsor/Collaborators	Start Date	Phases
臨床試験 (data from https://clinicaltrials.gov, updated on 2024-01-11)
NCT01341457	Completed	Solid Tumors	Eli Lilly and Company	May 2011	Phase 1
NCT01296568	Completed	Advanced Cancer	Eli Lilly and Company	February 2011	Phase 1
NCT01139775	Completed	Non Small Cell Lung Cancer	Eli Lilly and Company	February 2011	Phase 1\|Phase 2
NCT00988858	Completed	Non Small Cell Lung Cancer	Eli Lilly and Company	November 2009	Phase 2
NCT00839332	Completed	Pancreatic Neoplasms	Eli Lilly and Company	February 2009	Phase 1\|Phase 2

参考
[1] King C, et al. Invest New Drugs. 2014, 32(2):213-26. [2] Emiliano Calvo1, et al. Mol Cancer Ther, 2011, A94. [3] Govindan R. J Thorac Oncol, 2011, 6(11 Suppl 4), S1757. [4] Wang FZ, et al. Apoptosis. 2014, 19(9):1389-98. [5] Xin C, et al. Atherosclerosis. 2020 Nov;313:50-59. + 展開

参考

+ 展開

化学情報

分子量	436.3	化学式	C₁₈H₂₂BrN₅O₃
CAS No.	911222-45-2	SDF	Download Rabusertib (LY2603618) SDFをダウンロードする
Smiles	CC1=CC(=C(C=C1Br)NC(=O)NC2=NC=C(N=C2)C)OCC3CNCCO3
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 : 22 mg/mL ( (50.42 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。)

Water : Insoluble

Ethanol : 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。

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):