Elimusertib (BAY-1895344) hydrochloride

製品コードS8666 バッチS866601

化学情報

	Synonyms	BAY-1895344 HCl	Storage (From the date of receipt)	3 years -20°C powder 1 years -80°C in solvent
	化学式	C₂₀H₂₂ClN₇O
	分子量	411.89	CAS No.
Solubility (25°C)*	体外	DMSO	82 mg/mL (199.08 mM)
		Water	82 mg/mL (199.08 mM)
		Ethanol	82 mg/mL (199.08 mM)
* <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	Elimusertib (BAY-1895344) hydrochloride is a potent, highly selective and orally available ATR inhibitor with an IC50 of 7 nM.
in vitro	In vitro, BAY 1895344 is shown to be a very potent and highly selective ATR inhibitor (IC50 = 7 nM), which potently inhibits proliferation of a broad spectrum of human tumor cell lines (median IC50 = 78 nM). In cellular mechanistic assays BAY 1895344 potently inhibits hydroxyurea-induced H2AX phosphorylation (IC50 = 36 nM)^[1].
in vivo	BAY 1895344 reveals significantly improved aqueous solubility, bioavailability across species and no activity in the hERG patch-clamp assay. It also demonstrates very promising efficacy in monotherapy in DNA damage deficient tumor models as well as combination treatment with DNA damage inducing therapies^[1]. BAY 1895344 exhibits strong in vivo anti-tumor efficacy in monotherapy in a variety of xenograft models of different indications that are characterized by DDR deficiencies, inducing stable disease in ovarian and colorectal cancer or even complete tumor remission in mantle cell lymphoma models^[2].

製品説明

Elimusertib (BAY-1895344) hydrochloride is a potent, highly selective and orally available ATR inhibitor with an IC50 of 7 nM.

in vitro

In vitro, BAY 1895344 is shown to be a very potent and highly selective ATR inhibitor (IC50 = 7 nM), which potently inhibits proliferation of a broad spectrum of human tumor cell lines (median IC50 = 78 nM). In cellular mechanistic assays BAY 1895344 potently inhibits hydroxyurea-induced H2AX phosphorylation (IC50 = 36 nM)^[1].

in vivo

BAY 1895344 reveals significantly improved aqueous solubility, bioavailability across species and no activity in the hERG patch-clamp assay. It also demonstrates very promising efficacy in monotherapy in DNA damage deficient tumor models as well as combination treatment with DNA damage inducing therapies^[1].

BAY 1895344 exhibits strong in vivo anti-tumor efficacy in monotherapy in a variety of xenograft models of different indications that are characterized by DDR deficiencies, inducing stable disease in ovarian and colorectal cancer or even complete tumor remission in mantle cell lymphoma models^[2].

プロトコル(参考用のみ)

細胞アッセイ	細胞株	C4–2b and PC-3 cells
	濃度	2 μM
	反応時間	48 h
	実験の流れ	Cells were treated with various concentrations of BAY1895344.
動物実験	動物モデル	C57BL/6N male mice
	投薬量	40 mg/kg
	投与方法	i.p.

参考

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：

APOBEC3B coordinates R-loop to promote replication stress and sensitize cancer cells to ATR/Chk1 inhibitors [ Cell Death Dis, 2023, 14(6):348]	PubMed: 37270643
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
The effect of inhibition of receptor tyrosine kinase AXL on DNA damage response in ovarian cancer [ Commun Biol, 2023, 6(1):660]	PubMed: 37349576
Arginine shortage induces replication stress and confers genotoxic resistance by inhibiting histone H4 translation and promoting PCNA polyubiquitination [ bioRxiv, 2023, 2023.01.31.526362]	PubMed: 36778247
Genetically Defined, Syngeneic Organoid Platform for Developing Combination Therapies for Ovarian Cancer [ Cancer Discov, 2021, 11(2):362-383]	PubMed: 33158842
ATR inhibitor-induced CDK1-SPOP axis destabilizes PD-L1 and enhances cytotoxicity in prostate cancer [ Clin Cancer Res, 2021, clincanres.1010.2021]	PubMed: 34168048
ATR/ATM-Mediated Phosphorylation of BRCA1 T1394 Promotes Homologous Recombinational Repair and G2-M Checkpoint Maintenance [ Cancer Res, 2021, 81(18):4676-4684]	PubMed: 34301763
Double-strand breaks in ribosomal RNA genes activate a distinct signaling and chromatin response to facilitate nucleolar restructuring and repair [ Nucleic Acids Res, 2019, 10.1093/nar/gkz518]	PubMed: 31184714

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。

各々の製品のための特定の保管と取扱い情報は、製品データシートの上で示されます。大部分のSelleck製品は、推薦された状況の下で安定です。製品は、推薦された保管温度と異なる温度で、時々出荷されます。長期の保管のために必要とされてそれと異なる温度で、多くの製品は、短期もので安定です。品質を維持するが、夜通しの積荷のために最も経済的な貯蔵状況を用いてあなたの送料を保存する状況の下に、製品が出荷されることを、我々は確実とします。製品の受領と同時に、製品データシートの上で貯蔵推薦に従ってください。