Rabusertib (LY2603618)

製品コードS2626 バッチS262608

印刷

化学情報

Synonyms

IC-83

Storage
(From the date of receipt)

3 years -20°C powder
1 years -80°C in solvent

化学式

C₁₈H₂₂BrN₅O₃

分子量

436.3

CAS No.

911222-45-2

Solubility (25°C)*

体外

DMSO

29 mg/mL (66.46 mM)

Water

Insoluble

Ethanol

Insoluble

体内（毎回新しく調製した物を用意してください）

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。	1.000mg/ml (2.29mM)	Taking the 1 mL working solution as an example, add 50 μL of 20 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 clarify; 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.

* <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	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.
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, this compound prevents the repair of DNA caused by DNA-damaging agents, thus potentiating the antitumor efficacies of various chemotherapeutic agents. However, preclinical data involving this compound has not been published until now. ^[1] Inhibition of Chk1 is predicted to enhance the effects of antimetabolites. ^[2] This chemical treatment impairs DNA synthesis, increases DNA damage (via mitotic defects), induces apoptosis, and has synergistic activity, especially in p53 mutant tumor cells. ^[3]
in vivo	In xenograft models, this compound delays tumor growth when given in combination. ^[3]

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.

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, this compound prevents the repair of DNA caused by DNA-damaging agents, thus potentiating the antitumor efficacies of various chemotherapeutic agents. However, preclinical data involving this compound has not been published until now. ^[1]

Inhibition of Chk1 is predicted to enhance the effects of antimetabolites. ^[2]

This chemical treatment impairs DNA synthesis, increases DNA damage (via mitotic defects), induces apoptosis, and has synergistic activity, especially in p53 mutant tumor cells. ^[3]

in vivo

In xenograft models, this compound delays tumor growth when given in combination. ^[3]

プロトコル(参考用のみ)

細胞アッセイ	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 this compound 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.
動物実験	動物モデル	Male Wistar rats
	投薬量	50 mg/kg
	投与方法	i.p.

参考

https://pubmed.ncbi.nlm.nih.gov/24114124/
http://mct.aacrjournals.org/cgi/content/short/10/11_MeetingAbstracts/A94?rss=1
https://pubmed.ncbi.nlm.nih.gov/22005528/

https://pubmed.ncbi.nlm.nih.gov/24928205/
https://pubmed.ncbi.nlm.nih.gov/33027721/

+ 展开

カスタマーフィードバック

: Data from [Data independently produced by J Hematol Oncol, 2014, 7, 53]

: Data from [Data independently produced by Cancer Lett, 2014, 10.1016/j.canlet.2014.10.015]

: Data from [Data independently produced by BMC Cancer, 2014, 14, 483]

Selleckの高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：

KLF5 loss sensitizes cells to ATR inhibition and is synthetic lethal with ARID1A deficiency [ Nat Commun, 2025, 16(1):480]	PubMed: 39779698
DNA polymerase α/primase extraction from chromatin by VCP/p97 restricts ATR activation during unperturbed DNA replication [ Nat Commun, 2025, 16(1):5706]	PubMed: 40593507
USP37 counteracts HLTF to protect damaged replication forks and promote survival of BRCA1-deficient cells and PARP inhibitor resistance [ Nucleic Acids Res, 2025, 53(12)gkaf544]	PubMed: 40548939
The ribotoxic stress response drives UV-mediated cell death [ Cell, 2024, 187(14):3652-3670.e40]	PubMed: 38843833
Synergistic induction of mitotic pyroptosis and tumor remission by inhibiting proteasome and WEE family kinases [ Signal Transduct Target Ther, 2024, 9(1):181.]	PubMed: 38992067
The MYCN oncoprotein is an RNA-binding accessory factor of the nuclear exosome targeting complex [ Mol Cell, 2024, S1097-2765(24)00285-5]	PubMed: 38703770
FOXP1 phosphorylation antagonizes its O-GlcNAcylation in regulating ATR activation in response to replication stress [ EMBO J, 2024, 44(2):457-483.]	PubMed: 39623140
Synthetic lethality between ATR and POLA1 reveals a potential new target for individualized cancer therapy [ Neoplasia, 2024, 57:101038]	PubMed: 39128273
mTORC1 activity oscillates throughout the cell cycle promoting mitotic entry and differentially influencing autophagy induction [ bioRxiv, 2024, 2024.02.06.579216]	PubMed: 38370755
Mild replication stress causes premature centriole disengagement via a sub-critical Plk1 activity under the control of ATR-Chk1 [ Nat Commun, 2023, 14(1):6088]	PubMed: 37773176

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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