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RO-3306 {[allProObj[0].p_purity_real_show]}

货号:A138869

RO-3306是一种强效且选择性的 CDK1 抑制剂,对 CDK1/cyclin B1 的 Ki 值为 35 nM,选择性是 CDK2/cyclin E 和 CDK4/cyclin D 的 10 倍和 50 倍以上。

RO-3306 化学结构 CAS号:872573-93-8
RO-3306 化学结构
CAS号:872573-93-8
RO-3306 3D分子结构
CAS号:872573-93-8
RO-3306 化学结构 CAS号:872573-93-8
RO-3306 3D分子结构 CAS号:872573-93-8
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RO-3306 纯度/质量文件 产品仅供科研

货号:A138869 标准纯度: {[allProObj[0].p_purity_real_show]}
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产品名称 Cdc CDK1 CDK19 CDK2 CDK3 CDK4 CDK5 CDK6 CDK7 CDK8 CDK9 CLK 其他靶点 纯度
XL413 HCl ++++

Cdc7, IC50: 3.4 nM

99%+
SU9516 +++

CDK1, IC50: 40 nM

+++

CDK2, IC50: 22 nM

++

CDK4, IC50: 200 nM

99%+
RO-3306 +++

CDK1, Ki: 20 nM

ERK,SGK 98%
R547 ++++

CDK1/CyclinB, Ki: 2 nM

++++

CDK2/CyclinE, Ki: 3 nM

++++

CDK4/CyclinD1, Ki: 1 nM

99%+
BMS-265246 ++++

CDK1/CyclinB, IC50: 6 nM

++++

CDK2/CyclinE, IC50: 9 nM

+

CDK4/CyclinD, IC50: 230 nM

99%+
NU6027 +

CDK1, Ki: 2.5 μM

+

CDK2, Ki: 1.3 μM

DNA-PK 98%
Purvalanol A ++++

Cdc2/CyclinB, IC50: 4 nM

+++

CDK2/CyclinE, IC50: 35 nM

CDK2/CyclinA, IC50: 70 nM

+

CDK4/CyclinD1, IC50: 850 nM

99%+
SCH900776 ++

CDK2, IC50: 0.16 μM

99%+
AUZ 454 ++++

CDK2(A144C), Kd: 9.7 nM

CDK2(C118L), Kd: 18.6 nM

99%+
A-674563 HCl ++

CDK2, Ki: 46 nM

PKA 99%
JNJ-7706621 ++++

CDK1/CyclinB, IC50: 9 nM

++++

CDK2/CyclinE, IC50: 3 nM

CDK2/CyclinA, IC50: 4 nM

++

CDK3/CyclinE, IC50: 58 nM

+

CDK4/CyclinD1, IC50: 253 nM

++

CDK6/CyclinD1, IC50: 175 nM

99%+
AT7519 ++

CDK1/CyclinB, IC50: 210 nM

++

CDK2/CyclinA, IC50: 47 nM

+

CDK3/CyclinE, IC50: 360 nM

++

CDK4/CyclinD1, IC50: 100 nM

+++

CDK5/p35, IC50: 13 nM

++

CDK6/CyclinD3, IC50: 170 nM

++++

CDK9/CyclinT, IC50: <10 nM

98+%
PHA-793887 ++

CDK1/CyclinB, IC50: 60 nM

++++

CDK2/CyclinE, IC50: 8 nM

CDK2/CyclinA, IC50: 8 nM

++

CDK4/CyclinD1, IC50: 62 nM

++++

CDK5/p25, IC50: 5 nM

++++

CDK7/CyclinH, IC50: 10 nM

++

CDK9/CyclinT1, IC50: 138 nM

99%+
Milciclib +

CDK1/CyclinB, IC50: 398 nM

++

CDK2/CyclinE, IC50: 363 nM

CDK2/CyclinA, IC50: 45 nM

++

CDK4/CyclinD1, IC50: 160 nM

+

CDK5/p35, IC50: 265 nM

++

CDK7/CyclinH, IC50: 150 nM

99%+
Kenpaullone +

CDK1/CyclinB, IC50: 0.4μM

+

CDK2/CyclinE, IC50: 7.5μM

CDK2/CyclinA, IC50: 0.68μM

+

CDK5/p35, IC50: 0.85μM

98%
SNS-032 +++

CDK2/CyclinE, IC50: 48 nM

CDK2/CyclinA, IC50: 38 nM

+

CDK5/p35, IC50: 340 nM

++

CDK7/CyclinH, IC50: 62 nM

++++

CDK9/CyclinT, IC50: 4 nM

99%+
Dinaciclib ++++

CDK1, IC50: 3 nM

++++

CDK2, IC50: 1 nM

++++

CDK5, IC50: 1 nM

++++

CDK9, IC50: 4 nM

99%+
PHA-767491 HCl ++++

Cdc7, IC50: 10 nM

+

CDK1, IC50: 250 nM

+

CDK2, IC50: 240 nM

+

CDK5, IC50: 460 nM

+++

CDK9, IC50: 34 nM

MK2 99%
(R)-Roscovitine +

Cdc2/CyclinB, IC50: 0.65 μM

+

CDK2/CyclinE, IC50: 0.7 μM

CDK2/CyclinA, IC50: 0.7 μM

++

CDK5/p35, IC50: 0.16 μM

99%+
Narazaciclib ++++

CDK4/CyclinD1, IC50: 3.87 nM

++++

CDK6/CyclinD1, IC50: 9.82 nM

RET 99%+
Palbociclib ++++

CDK4/CyclinD1, IC50: 11 nM

CDK4/CyclinD3, IC50: 9 nM

+++

CDK6/CyclinD2, IC50: 15 nM

99%
Abemaciclib ++++

CDK4, IC50: 2 nM

++++

CDK6, IC50: 10 nM

99%
Ribociclib ++++

CDK4, IC50: 10 nM

+++

CDK6, IC50: 39 nM

98%
Palbociclib isethionate ++++

CDK4/CyclinD1, IC50: 11 nM

CDK4/CyclinD3, IC50: 9 nM

+++

CDK6/CyclinD2, IC50: 15 nM

99%+
BS-181 HCl +++

CDK7, IC50: 21 nM

99%+
(E/Z)-THZ1 2HCl ++++

CDK7, IC50: 3.2 nM

99%+
LDC4297 ++++

CDK7, IC50: 0.13 nM

99%+
Senexin A +

CDK19, Kd: 0.31 μM

+

CDK8, Kd: 0.83 μM

99%
MSC2530818 ++++

CDK8, IC50: 2.6 nM

99%+
Wogonin 99%+
Riviciclib HCl ++

CDK1/CyclinB, IC50: 79 nM

+

CDK2/CyclinE, IC50: 2.54 μM

CDK2/CyclinA, IC50: 224 nM

++

CDK4/CyclinD1, IC50: 63 nM

+

CDK6/CyclinD3, IC50: 396 nM

+

CDK7/CyclinH, IC50: 2.87 μM

+++

CDK9/CyclinT1, IC50: 20 nM

98%
LDC000067 +

CDK2, IC50: 2.441 μM

++

CDK9, IC50: 44 nM

98%
Flavopiridol +++

CDK1, IC50: 40 nM

+++

CDK2, IC50: 40 nM

+++

CDK4, IC50: 40 nM

+++

CDK6, IC50: 40 nM

+

CDK7, IC50: 300 nM

+++

CDK9, IC50: 20 nM

99%+
LY2857785 +

CDK7, IC50: 0.246 μM

+++

CDK8, IC50: 0.016 μM

+++

CDK9, IC50: 0.011 μM

99%+
AZD-5438 +++

CDK1, IC50: 16 nM

++++

CDK2, IC50: 6 nM

+++

CDK9, IC50: 20 nM

99%+
ML167 ++

CLK4, IC50: 136 nM

Dyrk1B , IC50: 1648 nM

99%+
(E/Z)-TG003 +++

mCLK1, IC50: 200 nM

mCLK4, IC50: 15 nM

99%+
1. 鼠标悬停在“+”上可以显示相关IC50的具体数值。"+"越多,抑制作用越强。2. "✔"表示该化合物对相应的亚型有抑制作用,但抑制强度暂时没有相关数据。

RO-3306 生物活性

靶点
  • CDK1

    CDK1, Ki:20 nM

描述 The CDKs (cyclin dependent kinases), as direct regulators of specific phases of the cell cycle, can control cellular proliferation and transcription with their activating cyclin partners and subunit inhibitors. CDK1, through forming complex with Cyclin A or B can trigger S-G2 and G2 to M transitions and G2 progression. RO-3306 is a selective CDK1 inhibitor with Ki value of 20nM (by the IMAP assay). Ro 3306 can reversibly arrest human cells at the G2/M border of the cell cycle and allows for effective cell synchronization in early mitosis. Treatment with 9uM RO-3306 for 20h caused significant decreased protein level of Cyclin E after 8h release from the nocodazole block, as well as Cyclin A and Cyclin B1 after 12h release from the nocodazole block, in HeLa cells synchronized in mitosis by a shake-off after 14 h of incubation in 100nM nocodazole (Cell transition through the G1 and S phase), without significantly affect cellular CDK2 and CDK4 function. HeLa cells traversed normally through the S phase in the presence of 9uM RO-3306 and effectively accumulated in the G2/M phase. Inhibition of CDK1 activity by 9uM RO-3306 forced HeLa cells in prometaphase to exit mitosis without cell division as indicated by the rapid disappearance of phosphohistone-H3 and chromatin decondensation, as well as rapid transition of Mcm2 from the soluble fraction to chromatin. Compared with MCF10A and MCF12A cells, treatement with 9 uM RO-3306 induced larger proapoptotic fraction, which showed that RO-3306 appeared to be more proapoptotic in cancer cells and may have utility as anticancer agents[1]. Combinatorial treatment RO3306 4mg/kg plus sorafenib 30mg/kg could suppress the tumor growth in hepatocellular carcinoma PDX models[2].
作用机制 Ro 3306 is an ATP-competitive CDK1 inhibitor. [1]

RO-3306 细胞实验

Cell Line
Concentration Treated Time Description References
HeLa cells 5 µM 15 min RO-3306 treatment induced dephosphorylation of Gwl at S90 and S453 sites and caused a downshift in Gwl migration band, indicating that RO-3306 promoted Gwl dephosphorylation by inhibiting Cdk1 activity. Elife. 2015 Dec 14;4:e10399.
HeLa cells 9 µM 20 h Used to synchronize cell divisions and fix cells at metaphase for subsequent experiments. Proc Natl Acad Sci U S A. 2023 Mar 7;120(10):e2120536120.
RPE1 cells 7.5 μM 18 h Synchronize RPE1 cells into G2 phase and arrest them in G2 phase by RO3306 treatment for subsequent cell cycle time course experiments. Mol Cell Proteomics. 2020 Sep;19(9):1450-1467.
HeLa cells 10 µM 12 h To study the effect of RO-3306 on HeLa cells synchronized at the G2/M border, results showed that RO-3306 inhibited Cdk1 activity and delayed mitotic entry. Sci Adv. 2018 Jun 6;4(6):eaap7777.
Glioma stem cells (GSCs) 20 μM 12 h Inhibits CDK1 activity, reduces serine phosphorylation of Ubc9, thereby attenuating the interaction between Pin1 and Ubc9. Nat Commun. 2024 Jan 2;15(1):40.
muscle satellite cells 0.5 μM 24 h Inhibit Cdk1/Ccnb1 activity, reduce BrdU incorporation in FoxM1-overexpressing muscle satellite cells Cell Death Dis. 2020 Mar 9;11(3):180.
HT1376 and HT1197 BC cells 20 μM 2 h RO-3306 increased the expression of ID2, indicating that CDK1 inhibition can enhance ID2 expression. Exp Mol Med. 2022 Jun;54(6):801-811.

RO-3306 动物实验

Species
Animal Model
Administration Dosage Frequency Description References
Mice Orthotopic GBM xenografts Intraperitoneal injection 20 mg/kg Every other day until the end of the experiments Inhibits CDK1 activity, reduces SUMO1-modified protein sumoylation, suppresses tumor growth, and extends mouse survival. Nat Commun. 2024 Jan 2;15(1):40.
Mice FoxM1-overexpressing mice Intraperitoneal injection 4 mg/kg 4 times per week for 5 weeks Inhibit Cdk1/Ccnb1 activity, restore the muscle satellite cell pool in FoxM1-overexpressing mice Cell Death Dis. 2020 Mar 9;11(3):180.
NSG immunodeficient mice Orthotopic BC xenograft model Intraperitoneal injection 4 mg/kg Every 4 days, 6 times RO-3306 monotherapy inhibited 33.2% of tumor growth, and combination with apigenin inhibited 63.1% of tumor growth, indicating that RO-3306 enhanced the antitumor effect of apigenin. Exp Mol Med. 2022 Jun;54(6):801-811.
Nude mice Breast cancer xenograft model Intraperitoneal injection 4 mg/kg Every 2 days until sacrifice To examine the effect of CDK1 inhibitor RO-3306 on tumor growth, results showed that RO-3306 significantly inhibited tumor growth. Adv Sci (Weinh). 2023 Apr;10(11):e2205873.

RO-3306 参考文献

[1]Vassilev LT, Tovar C, et al. Selective small-molecule inhibitor reveals critical mitotic functions of human CDK1. Proc Natl Acad Sci U S A. 2006 Jul 11;103(28):10660-5. Epub 2006 Jul 3.

[2]Wu CX, Wang XQ, et al. Blocking CDK1/PDK1/β-Catenin signaling by CDK1 inhibitor RO3306 increased the efficacy of sorafenib treatment by targeting cancer stem cells in a preclinical model of hepatocellular carcinoma. Theranostics 2018; 8(14):3737-3750.

RO-3306 实验方案

计算器
存储液制备 1mg 5mg 10mg

1 mM

5 mM

10 mM

2.85mL

0.57mL

0.28mL

14.23mL

2.85mL

1.42mL

28.45mL

5.69mL

2.85mL

RO-3306 技术信息

CAS号872573-93-8
分子式C18H13N3OS2
分子量 351.45
SMILES Code O=C1N=C(NCC2=CC=CS2)S/C1=C/C3=CC=C4N=CC=CC4=C3
MDL No. MFCD17392573
别名
运输蓝冰
InChI Key XOLMRFUGOINFDQ-YBEGLDIGSA-N
Pubchem ID 135400873
存储条件

In solvent -20°C: 3-6个月 -80°C: 12个月

Pure form Keep in dark place, sealed in dry, 2-8°C

溶解方案

DMSO: 25 mg/mL(71.13 mM),配合低频超声助溶,注意:DMSO长时间开封后,会吸水并导致溶解能力下降,请避免使用长期开封的DMSO

请根据您的动物给药指南选择适当的溶解方案。
以下溶解方案都请先按照体外实验的方式配制澄清的储备液,再依次添加助溶剂:
——为保证实验结果的可靠性,澄清的储备液可以根据储存条件,适当保存;体内实验的工作液,建议现用现配,当天使用; 以下溶剂前显示的百分比是指该溶剂在终溶液中的体积占比;如在配制过程中出现沉淀、析出现象,可以通过加热和/或超声的方式助溶
方案 一
方案 二
配制的工作液建议现用现配,短期内尽快用完。 以下溶剂前显示的百分比是指该溶剂在终溶液中的体积占比;如在配制过程中出现沉淀、析出现象,可以通过加热和/或超声的方式助溶
方案 一
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