JNJ-7706621

製品コードS1249 バッチS124901

化学情報

	Synonyms	N/A	Storage (From the date of receipt)	3 years -20°C powder 1 years -80°C in solvent
	化学式	C₁₅H₁₂F₂N₆O₃S
	分子量	394.36	CAS No.	443797-96-4
Solubility (25°C)*	体外	DMSO	79 mg/mL (200.32 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	JNJ-7706621 is a pan-CDK inhibitor with the highest potency on CDK1/2 with IC50 of 9 nM/4 nM and showing >6-fold selectivity for CDK1/2 than CDK3/4/6 in cell-free assays. It also potently inhibits Aurora A/B and has no activity on Plk1 and Wee1.
in vitro	JNJ-7706621 also shows some inhibition to VEGF-R2, FGF-R2, and GSK3β, with IC50 of 154-254 nM. JNJ-7706621 shows inhibitory effect on a panel of human cancer cell types, including HeLa, HCT-116, SK-OV-3, PC3, DU145, A375, MDA-MB-231, MES-SA, and MES-SA/Dx5, with IC50 of 112-514 nM, independent of p53, retinoblastoma, or P-glycoprotein status. JNJ-7706621 is several-fold less potent at inhibiting growth of normal cell types, including MRC-5, HASMC, HUVEC, and HMVEC, with IC50 of 3.67-5.42 μM. In HeLa or U937 cells, JNJ-7706621 (0.5-3 μM) delays exit from G1, arrests cells in G2-M, induces endoreduplication, activates apoptosis, and reduces colony formation. ^[1] In a HeLa cell line, incremental treatment with increasing concentrations of JNJ-7706621 leads to a 16-fold resistance, which may be mediated by ABCG2. ^[2]
in vivo	In mouse xenograft model of A375 melanoma human tumor, JNJ-7706621 (100 or 125 mg/kg) causes tumor regression. ^[3]
特徴	A broad-spectrum inhibitor.

プロトコル(参考用のみ)

キナーゼアッセイ	In vitro kinase assay for CDK1 and Aurora kinases
キナーゼアッセイ	For CDK1 kinase activity, a method is developed using the CDK1/cyclin B complex purified from baculovirus to phosphorylate a biotinylated peptide substrate containing the consensus phosphorylation site for histone H1, which is phosphorylated in vivo by CDK1. Inhibition of CDK1 activity is measured by observing a reduced amount of ³³P-γ-ATP incorporation into the immobilized substrate in streptavidin-coated 96-well scintillating microplates. CDK1 enzyme is diluted in 50 mM Tris-HCl (pH 8), 10 mM MgCl₂, 0.1 mM Na₃VO ₄, 1 mM DTT, 1% DMSO, 0.25 μM peptide, 0.1 μCi per well ³³P-γ-ATP, and 5 μM ATP in the presence or absence of various concentrations of JNJ-7706621 and incubated at 30 °C for 1 hour. The reaction is terminated by washing with PBS containing 100 mM EDTA and plates are counted in a scintillation counter. Linear regression analysis of the percent inhibition by JNJ-7706621 is used to determine IC50. The Aurora kinase assays are done with 10 μM ATP and a peptide containing a dual repeat of the kemptide phosphorylation motif.
細胞アッセイ	細胞株	HeLa, HCT-116, A375, SK-OV-3, MDA-MB-231, and PC-3 cells
	濃度	1 nM - 10 μM, dissolved in DMSO
	反応時間	48 hours
	実験の流れ	The ability of JNJ-7706621 to inhibit the proliferation of cell growth is determined by measuring incorporation of ¹⁴C-labelled thymidine into newly synthesized DNA within the cells. Cells are trypsinized and counted and 3-8 × 10³ cells are added to each well of a 96-well CytoStar tissue culture treated scintillating microplate in complete medium in a volume of 100 μL. Cells are incubated for 24 hours in complete medium at 37 °C in an atmosphere containing 5% CO₂. Next, 1 μL of JNJ-7706621 is added to the wells of the plate. Cells are incubated for 24 more hours. Methyl ¹⁴C-thymidine 56 mCi/mmol is diluted in complete medium and 0.2 μCi/well is added to each well of the CytoStar plate in a volume of 20 μL. The plate is incubated for 24 hours at 37 °C in JNJ-7706621 plus ¹⁴C-thymidine. The contents of the plate are discarded and the plate is washed twice with 200 μL PBS. 200 μL of PBS is added to each well. The top of the plate is sealed with a transparent plate sealer and a white plate backing sealer is applied to the bottom of the plate. The degree of methyl ¹⁴C-thymidine incorporation is quantified on a Packard Top Count.
動物実験	動物モデル	Mouse xenograft model of A375 cells
	投薬量	100 or 125 mg/kg
	投与方法	Orally or by intraperitoneal injection injection

参考

カスタマーフィードバック

: Data from [Data independently produced by Oncogene, 2014, 10.1038/onc.2014.351]

: Data from [Data independently produced by Mol Cancer Ther, 2014, 13(3), 662-74]

: , , Dr. Zhang of Tianjin Medical University

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：

Inhibitors of One or More Cellular Aurora Kinases Impair the Replication of Herpes Simplex Virus 1 and Other DNA and RNA Viruses with Diverse Genomes and Life Cycles [ Microbiol Spectr, 2023, 11(1):e0194322]	PubMed: 36537798
Integrative analysis of drug response and clinical outcome in acute myeloid leukemia [ Cancer Cell, 2022, S1535-6108(22)00312-9]	PubMed: 35868306
Nascent transcriptome reveals orchestration of zygotic genome activation in early embryogenesis [ Curr Biol, 2022, 32(19):4314-4324.e7]	PubMed: 36007528
Inhibition of IκB Kinase Is a Potential Therapeutic Strategy to Circumvent Resistance to Epidermal Growth Factor Receptor Inhibition in Triple-Negative Breast Cancer Cells [ Cancers (Basel), 2022, 14(21)5215]	PubMed: 36358633
Dual Inhibition of AKT and MEK Pathways Potentiates the Anti-Cancer Effect of Gefitinib in Triple-Negative Breast Cancer Cells [ Cancers (Basel), 2021, 13(6)1205]	PubMed: 33801977
Transcriptome Analysis and Functional Identification of Adipose-Derived Mesenchymal Stem Cells in Secondary Lymphedema [ Gland Surg, 2020, 9(2):558-574]	PubMed: 32420291
The TRAPP complex mediates secretion arrest induced by stress granule assembly. [ EMBO J, 2019, 38(19):e101704]	PubMed: 31429971
DRUGPATH - a novel bioinformatic approach identifies DNA-damage pathway as a regulator of size maintenance in human ESCs and iPSCs [ Sci Rep, 2019, 9(1):1897]	PubMed: 30760778
CDK9 modulates circadian clock by attenuating REV-ERBα activity. [ Biochem Biophys Res Commun, 2019, 513(4):967-973]	PubMed: 31005255
Targeted Polo-like Kinase Inhibition Combined With Aurora Kinase Inhibition in Pediatric Acute Leukemia Cells. [ J Pediatr Hematol Oncol, 2019, 41(6):e359-e370]	PubMed: 30702467

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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