Rabusertib (LY2603618)

製品コードS2626 バッチS262606

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	13 mg/mL (29.79 mM)
		Water	Insoluble
		Ethanol	Insoluble
* <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, 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]
in vivo	In xenograft models, LY2603618 delays tumor growth when given in combination with pemetrexed. ^[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, 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]

in vivo

In xenograft models, LY2603618 delays tumor growth when given in combination with pemetrexed. ^[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 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.
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

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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：

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
An ATR-PrimPol pathway confers tolerance to oncogenic KRAS-induced and heterochromatin-associated replication stress [ Nat Commun, 2023, 14(1):4991]	PubMed: 37591859
An ATR-PrimPol pathway confers tolerance to oncogenic KRAS-induced and heterochromatin-associated replication stress [ Nat Commun, 2023, 14(1):4991]	PubMed: 37591859
Actionable loss of SLF2 drives B-cell lymphomagenesis and impairs the DNA damage response [ EMBO Mol Med, 2023, e16431.]	PubMed: 37485814
Pharmacological tumor PDL1 depletion with chlorambucil treats ovarian cancer and melanoma: improves antitumor immunity and renders anti-PDL1-resistant tumors anti-PDL1-sensitive through NK cell effects [ J Immunother Cancer, 2023, 11(2)e004871]	PubMed: 36759012
VPA mediates bidirectional regulation of cell cycle progression through the PPP2R2A-Chk1 signaling axis in response to HU [ Cell Death Dis, 2023, 14(2):114]	PubMed: 36781846
Arginine shortage induces replication stress and confers genotoxic resistance by inhibiting histone H4 translation and promoting PCNA ubiquitination [ Cell Rep, 2023, 42(4):112296]	PubMed: 36961817
Mitotic perturbation is a key mechanism of action of decitabine in myeloid tumor treatment [ Cell Rep, 2023, 42(9):113098]	PubMed: 37714156
BRD7 suppresses tumor chemosensitivity to CHK1 inhibitors by inhibiting USP1-mediated deubiquitination of CHK1 [ Cell Death Discov, 2023, 9(1):313]	PubMed: 37626049

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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