Purvalanol A 是一种 CDK2 抑制剂,对 cdc2-cyclin B、cdk2-cyclin A、cdk2-cyclin E、cdk4-cyclin D1 和 cdk5-p35 的 IC50 值分别为 4、70、35、850、75 nM。


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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 |
SGK,ERK | 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(C118L), Kd: 18.6 nM CDK2(A144C), Kd: 9.7 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/CyclinD3, IC50: 9 nM CDK4/CyclinD1, IC50: 11 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/CyclinD3, IC50: 9 nM CDK4/CyclinD1, IC50: 11 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 |
++
Dyrk1B , IC50: 1648 nM CLK4, IC50: 136 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 | CDK2 is a serine/threonine-protein kinase involved in the control of the cell cycle; essential for meiosis, but dispensable for mitosis. CDK2 triggers duplication of centrosomes and DNA, acts at the G1-S transition to promote the E2F transcriptional program and the initiation of DNA synthesis, and modulates G2 progression. CDK2 controls the timing of entry into mitosis/meiosis by controlling the subsequent activation of cyclin B/CDK1 by phosphorylation, and coordinates the activation of cyclin B/CDK1 at the centrosome and in the nucleus. Purvalanol A is a CDK2 inhibitor, which inhibits cdc2-cyclin B, cdk2-cyclin A, cdk2-cyclin E, cdk4-cyclin D1, and cdk5-p35 with IC50s of 4, 70, 35, 850, 75 nM, respectively. Based on kinase assays performed in immunoprecipitates, the IC50s of purvalanol A against 2 yeast CDKs (Cdc28p and Pho85p) were 7 μM and 2 μM, respectively[3]. According to a MTT cell viability assay, purvalanol A induced cell viability loss by 50% in MCF-7 cells at the concentration of 25 μM when incubated in vitro for 24h[4].In a spinal cord injury model established in Sprague–Dawley rats, 5 μl of purvalanol A at the concentration of 10 mM in DMSO was immediately injected into the injury site. The results were that purvalanol A restricted compaction of the injury cavity and astrocyte infiltration into the cavity. Purvalanol A treatment also attenuated regenerative responses of anterogradely labeled corticospinal tract axons. Moreover, purvalanol A treatments reduced astrocyte migration and in parallel retarded the extension of spinal axon, observed by the technique of implantation of a polymeric tube into the spinal cord[5]. |
| 作用机制 | Purvalanol A is a CDK2 inhibitor that acts by blocking the ATP-binding site[3]. |
| Concentration | Treated Time | Description | References | |
| Human foreskin fibroblasts (HFFs) | 20 µM | 2 days | To evaluate the antiviral effects of Purvalanol A on VZV replication, results showed that Purvalanol A exhibited antiviral activity in cultured HFFs. | Antiviral Res. 2010 Jun;86(3):276-85. |
| HeLa cells | 25 µM | 2 hours | To investigate the effect of Purvalanol A on mitotic exit in HeLa cells in the presence of MG132, results showed that Purvalanol A was unable to drive mitotic exit. | J Cell Biol. 2007 Nov 19;179(4):671-85. |
| Jurkat cells | 20 µM | 24 hours | Purvalanol A repressed the levels of DHFR protein and enhanced sensitivity to MTX in Jurkat cells. | Cancer Sci. 2010 Mar;101(3):728-34. |
| Giardia lamblia | 10 µM | 24 hours | To study the effect of Purvalanol A on Cdk2 kinase activity. Results showed that addition of purvalanol A significantly decreased the Cdk2-associated kinase activity. | J Biol Chem. 2012 Feb 3;287(6):3733-50. |
| Human umbilical vein endothelial cells | 10 µM | 30 minutes to 1 hour | To investigate the effect of Purvalanol A on CA-4-P-induced mitotic arrest, results showed that Purvalanol A accelerated the progression of cells through mitosis. | Am J Pathol. 2004 Oct;165(4):1401-11. |
| Tet-BZLF1/Akata cells | 5 µM | 48 hours | Inhibited EBV lytic protein expression, almost completely blocking viral protein production | J Virol. 2004 Jan;78(1):104-15. |
| C. elegans embryos | 100 mM | 5 minutes | To study the effect of CDK-1 inhibition on meiotic spindle rotation, results showed that PA treatment caused spindle rotation and shortening. | elegans. J Cell Biol. |
| Kasumi-1 | 0.1 µM and 0.5 µM | 72 hours | To evaluate the cytotoxicity of Purvalanol A in combination with ABT-737 on Kasumi-1 cells. Results showed that the combination significantly increased cell death compared to single agents. | Int J Mol Sci. 2023 Mar 16;24(6):5717. |
| MV4-11 | 0.1 µM and 0.5 µM | 72 hours | To evaluate the cytotoxicity of Purvalanol A in combination with ABT-737 on MV4-11 cells. Results showed that the combination significantly increased cell death compared to single agents. | Int J Mol Sci. 2023 Mar 16;24(6):5717. |
| CMK | 0.1 µM and 0.5 µM | 72 hours | To evaluate the cytotoxicity of Purvalanol A in combination with ABT-737 on CMK cells. Results showed that the combination significantly increased cell death compared to single agents. | Int J Mol Sci. 2023 Mar 16;24(6):5717. |
| Tet-BZLF1/B95-8 cells | 15 µM | 72 hours | Inhibited EBV lytic replication, almost completely blocking viral DNA amplification | J Virol. 2004 Jan;78(1):104-15. |
| MV4-11 cells | 1.3 µM | 72 hours | Evaluate the effects of Purvalanol A alone or in combination with ABT-737 on cell viability, showing that the combined treatment significantly enhanced cytotoxicity. | Biomacromolecules. 2024 Oct 14;25(10):6503-6514. |
| MOLM-13 cells | 1.3 µM | 72 hours | Evaluate the effects of Purvalanol A alone or in combination with ABT-737 on cell viability, showing that the combined treatment significantly enhanced cytotoxicity. | Biomacromolecules. 2024 Oct 14;25(10):6503-6514. |
| MOLM-14 cells | 1.3 µM | 72 hours | Evaluate the effects of Purvalanol A alone or in combination with ABT-737 on cell viability, showing that the combined treatment significantly enhanced cytotoxicity. | Biomacromolecules. 2024 Oct 14;25(10):6503-6514. |
| HPV31b-positive keratinocytes | 10 nM | from day 8 to day 12 | Inhibition of CDK1 kinase activity resulted in the synthesis of noninfectious HPV31b particles | J Virol. 2010 May;84(9):4630-45. |
| Administration | Dosage | Frequency | Description | References | ||
| C. elegans | Wild-type and APC mutant embryos | Uterine injection | 100 mM | Single injection, lasting 5 minutes | To study the effect of CDK-1 inhibition on meiotic spindle rotation, results showed that PA treatment caused spindle rotation and shortening. | elegans. J Cell Biol. |
| SCID-Hu mice | Skin xenograft model | Intraperitoneal injection | 20 mg/kg/day and 10 mg/kg/day | Once daily for 7 days | To evaluate the antiviral effects of Purvalanol A in the SCID-Hu mouse model, results showed that Purvalanol A failed to effectively inhibit VZV replication. | Antiviral Res. 2010 Jun;86(3):276-85. |
| Dose | Mice: 30 mg/kg[3] (i.v.) |
| Administration | i.v. |
| 计算器 | ||||
| 存储液制备 | ![]() |
1mg | 5mg | 10mg |
|
1 mM 5 mM 10 mM |
2.57mL 0.51mL 0.26mL |
12.86mL 2.57mL 1.29mL |
25.71mL 5.14mL 2.57mL |
|
| CAS号 | 212844-53-6 |
| 分子式 | C19H25ClN6O |
| 分子量 | 388.89 |
| SMILES Code | CC(C)[C@@H](NC1=NC(NC2=CC=CC(Cl)=C2)=C3N=CN(C(C)C)C3=N1)CO |
| MDL No. | MFCD02179211 |
| 别名 | NG-60 |
| 运输 | 蓝冰 |
| InChI Key | PMXCMJLOPOFPBT-HNNXBMFYSA-N |
| Pubchem ID | 456214 |
| 存储条件 |
In solvent -20°C: 3-6个月 -80°C: 12个月 Pure form Keep in dark place, inert atmosphere, store in freezer, under -20°C |
| 溶解方案 |
DMSO: 50 mg/mL(128.57 mM),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 无水乙醇: 8 mg/mL(20.57 mM),配合低频超声助溶,注意:无水乙醇开封后,易挥发,也会吸收空气中的水分,导致溶解能力下降,请避免使用开封较久的乙醇 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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