BAY 1000394

製品コードS7047 バッチS704701

印刷

化学情報

Synonyms

Roniciclib

Storage
(From the date of receipt)

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

化学式

C₁₈H₂₁F₃N₄O₃S

分子量

430.44

CAS No.

1223498-69-8

Solubility (25°C)*

体外

DMSO

86 mg/mL (199.79 mM)

Ethanol

86 mg/mL (199.79 mM)

Water

Insoluble

体内（毎回新しく調製した物を用意してください）

Clear solution	5%DMSO 1 40%PEG300 2 5%Tween80 3 50%ddH2O	4.3mg/ml	Taking the 1 mL working solution as an example, add 50 μL of 86 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.
Clear solution	5% DMSO 1 95% Corn oil	0.7mg/ml	Taking the 1 mL working solution as an example, add 50 μL of 14 mg/ml clear DMSO stock solution to 950 μL of corn oil and mix evenly. 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	BAY 1000394 (Roniciclib) is a potent inhibitor of pan-CDK, that inhibits the kinase activity of the cell-cycle cyclin-dependent kinases (CDKs), with IC50 of 7, 9, 11, 25 and 5 nmol/L for CDK1, CDK2, CDK4, CDK7 and CDK9, respectively. It induces cell-cycle arrest and apoptosis and exhibits potent antitumor activity.
in vitro	BAY 1000394 inhibits the kinase activity of the cell-cycle CDKs CDK1/cyclin B, CDK2/cyclin E, and CDK4/cyclin D with IC50 values of 7, 9, and 11 nM, respectively. The transcriptional CDKs CDK9/cyclin T1 and CDK7/cyclin H/MAT1 are also inhibited by BAY 1000394 in a similar range (5 and 25 nM), as well as the other CDK family members, classifying BAY 1000394 as a pan-CDK inhibitor. BAY 1000394 simultaneously inhibits cell-cycle progression and of RNA polymerase II-mediated gene transcription. On a panel of 214 non-CDK Ser/Thr and Tyr kinases, 16 additional kinases are found to be inhibited by BAY 1000394 with IC50 values below 100 nM. BAY 1000394 displays broad and uniform inhibitory activity on cancer cell proliferation with IC50s values between 9 and 79 nM (mean 39 nM) for a panel of 40 human lung tumor cell lines, and IC50s between 6 an d 84 nM (mean 37 nM) for a panel of 24 human breast tumor and immortalized cell lines. Within these panels, which represent a broad range of genetic backgrounds (p53, pRB, K-Ras, PGP, etc.), no cell line could be identified that is poorly sensitive towards treatment with BAY 1000394. Antiproliferative activity of BAY 1000394 is associated with the induction of apoptotic cell death. Exposure of asynchronously growing HeLa cells to BAY 1000394 for 24 hours reduces the fraction of cells with 2N content, from 69% to 52% compared with vehicle treated cells and strongly increases the fraction of cells with less than 2N DNA content from 1% to 16%. Only minor shifts are observed for cells in S, G2, or M phase. ^[1]
in vivo	BAY 1000394 shows potent tumor growth inhibition in monotreatment upon oral application in various dosing schedules in a dose-dependent manner, activity in models of treatment-refractory tumors, and efficacy in cell-line–derived as well as in patient tumor–derived models. BAY 1000394 (2 mg/kg) suppresses growth of HeLa-MaTu xenografts tumor with T/C values of 0.03 and signs of tumor regression. BAY 1000394 shows additive efficacy in combination with cisplatin. Addition of BAY 1000394 to cisplatin results in a strong tumor growth inhibition of NCI-H82 SCLC xenograft tumors with T/C values of 0.01 (1.0 mg/kg BAY 1000394) and -0.02 (1.5 mg/kg BAY 1000394). ^[1]

プロトコル(参考用のみ)

キナーゼアッセイ	Kkinase assays
キナーゼアッセイ	Recombinant CDK1 and CycB-GST fusion proteins, and CDK2 and CycE-GST fusion proteins, are purified from baculovirus-infected Sf9 insect cells. Histon IIIS is used as kinase substrate. Inhibition of kinase activity is determined by substrate phosphorylation assays using ^{3P-gamma adenosine triphosphate. BAY 1000394 is counter screened against a panel of 220 kinases using the Kinase profiler screen at 500 nM.}
細胞アッセイ	細胞株	Human cervical cancer cell HeLa-MaTu
	濃度	~10 μM
	反応時間	4 days
	実験の流れ	Proliferation assays are conducted in 96 well plates at densities between 1,000 and 5,000 cells per well in the appropriate medium containing 10% fetal calf serum (FCS). Cells are treated in quadruplicates with serial dilutions of BAY 1000394 for 96 hours followed by quantification of relative cell numbers upon crystal violet staining. BAY 1000394 is profiled on panels of 40 human lung and 24 human breast cell lines using the Oncology Profiling Service.
動物実験	動物モデル	Human cervical cancer xenografts HeLa-MaTu
	投薬量	2 mg/kg
	投与方法	p.o. once daily for 21 days

参考

[1] Siemeister G, et al. Mol Cancer Ther, 2012, 11(10), 2265-2273.

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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