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。


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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。 | |||||||||||||||||||
| 靶点 |
|
| 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] |
| 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. |
| 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. |
| 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 |
|
| 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 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
|
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