VE-821

製品コードS8007 バッチS800703

化学情報

	Synonyms	ATR inhibitor IV	Storage (From the date of receipt)	3 years -20°C powder 1 years -80°C in solvent
	化学式	C₁₈H₁₆N₄O₃S
	分子量	368.41	CAS No.	1232410-49-9
Solubility (25°C)*	体外	DMSO	74 mg/mL (200.86 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	VE-821(ATR inhibitor IV) is a potent and selective ATP competitive inhibitor of ATR with K_i/IC50 of 13 nM/26 nM in cell-free assays, shows inhibition of H2AX phosphorylation, minimal activity against PIKKs ATM, DNA-PK, mTOR and PI3Kγ.
in vitro	VE-821(ATR inhibitor IV) shows excellent selectivity for ATR with minimal cross-reactivity against the related PIKKs ATM, DNA-PK, mTOR and PI3K (K_is of 16 μM, 2.2 μM, >1 μM and 3.9 μM, respectively. VE-821 alone commits a large fraction of cancer cell populations to death, but it only reversibly limits cell cycle progression in normal cells, with minimal death or long-term detrimental effects. VE-821 along with cisplatin treatment shows the most marked synergy. ^[1] VE-821(ATR inhibitor IV) inhibits H2AX cell growth with IC50 of 800 nM. ^[2]
in vivo	VE-821(ATR inhibitor IV) is a potent and selective ATP competitive inhibitor of ATR.

製品説明

VE-821(ATR inhibitor IV) is a potent and selective ATP competitive inhibitor of ATR with K_i/IC50 of 13 nM/26 nM in cell-free assays, shows inhibition of H2AX phosphorylation, minimal activity against PIKKs ATM, DNA-PK, mTOR and PI3Kγ.

in vitro

VE-821(ATR inhibitor IV) shows excellent selectivity for ATR with minimal cross-reactivity against the related PIKKs ATM, DNA-PK, mTOR and PI3K (K_is of 16 μM, 2.2 μM, >1 μM and 3.9 μM, respectively. VE-821 alone commits a large fraction of cancer cell populations to death, but it only reversibly limits cell cycle progression in normal cells, with minimal death or long-term detrimental effects. VE-821 along with cisplatin treatment shows the most marked synergy. ^[1]

VE-821(ATR inhibitor IV) inhibits H2AX cell growth with IC50 of 800 nM. ^[2]

in vivo

VE-821(ATR inhibitor IV) is a potent and selective ATP competitive inhibitor of ATR.

プロトコル(参考用のみ)

キナーゼアッセイ	Kinase inhibition
キナーゼアッセイ	The ability of compounds to inhibit ATR, ATM or DNAPK kinase activity istested using a radiometric-phosphate incorporation assay. A stock solution isprepared consisting of the appropriate buffer, kinase, and target peptide. To this isadded the compound of interest, at varying concentrations in DMSO to a final DMSO concentration of 7%. Assays are initiated by addition of an appropriate [γ-³³P]ATP solution and incubated at 25 ℃. Assays are stopped, after the desired time course, by addition of phosphoric acid and ATP to a final concentration of 100 mM and 0.66μM, respectively. Peptides are captured on a phosphocellulose membrane, prepared as per manufacturer
細胞アッセイ	細胞株	H2AX cells
	濃度	--
	反応時間	96 hours
	実験の流れ	Cells are plated in 96-well plates and allowed to adhere overnight. The following day, compounds are added at the indicated concentrations in a final volume of 200μL, and the cells are then incubated for 96 h. MTS reagent (40μL) isthen added, and 1 h later, absorbance at 490 nm ismeasured using a SpectraMax Plus 384 plate reader. Synergy and antagonism are assessed using Macsynergy software.
動物実験	動物モデル	Male immunodefcient mice
	投薬量	15 mg/kg
	投与方法	i.p.

参考

カスタマーフィードバック

: Data from [Data independently produced by Toxicol Sci, 2014, 10.1093/toxsci/kfu207]

: Data from [Data independently produced by J Biol Chem, 2014, 289(35), 24314-24]

: Data from [Data independently produced by , , Nature, 2018, 555(7696):387-391]

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：

Comprehensive multi-omics analysis reveals WEE1 as a synergistic lethal target with hyperthermia through CDK1 super-activation [ Nat Commun, 2024, 15(1):2089]	PubMed: 38453961
Immunomodulatory effects and improved outcomes with cisplatin- versus carboplatin-based chemotherapy plus atezolizumab in urothelial cancer [ Cell Rep Med, 2024, 5(2):101393]	PubMed: 38280376
ATR limits Rad18-mediated PCNA monoubiquitination to preserve replication fork and telomerase-independent telomere stability [ EMBO J, 2024, 43(7):1301-1324]	PubMed: 38467834
DNA damage remodels the MITF interactome to increase melanoma genomic instability [ Genes Dev, 2024, 38(1-2):70-94]	PubMed: 38316520
The ARID1A-METTL3-m6A axis ensures effective RNase H1-mediated resolution of R-loops and genome stability [ Cell Rep, 2024, 43(2):113779]	PubMed: 38358891
Large tandem duplications in cancer result from transcription and DNA replication collisions [ medRxiv, 2024, 2023.05.17.23290140]	PubMed: 38260434
Polθ is phosphorylated by PLK1 to repair double-strand breaks in mitosis [ Nature, 2023, 621(7978):415-422]	PubMed: 37674080
ATM signaling modulates cohesin behavior in meiotic prophase and proliferating cells [ Nat Struct Mol Biol, 2023, 10.1038/s41594-023-00929-5]	PubMed: 36879153
CDC7 inhibition induces replication stress-mediated aneuploid cells with an inflammatory phenotype sensitizing tumors to immune checkpoint blockade [ Nat Commun, 2023, 10.1038/s41467-023-43274-3]	PubMed: 37980406
ATM-ESCO2-SMC3 axis promotes 53BP1 recruitment in response to DNA damage and safeguards genome integrity by stabilizing cohesin complex [ Nucleic Acids Res, 2023, gkad533]	PubMed: 37377435

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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