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Purity: ≥98%
Purvalanol A (NG60; NG-60; NG 60) is a potent and cell-permeable CDK (cyclin-dependent kinase) inhibitor with potential antitumor activity. It has IC50 values of 4 nM, 70 nM, 35 nM, and 850 nM for cdc2-cyclin B, cdk2-cyclin A, cdk2-cyclin E, and cdk4-cyclin D1 inhibition, respectively. Purvalanol A (30 μM) caused apoptosis in MKN45 cells by downregulating the expression of the antiapoptotic proteins survivin, Bcl-XL, and Bcl-2. Additionally, purvalanol A inhibited the expression and phosphorylation of RNA polymerase II, which was involved in transcriptional regulation, as well as the phosphorylation of STAT3 by Janus kinase 2 (JAK2).
| Targets |
cdc2-cyclin B (IC50 = 4 nM); cdk2-cyclin E (IC50 = 35 nM); cdk2-cyclin A (IC50 = 70 nM); cdk4-cyclin D1 (IC50 = 850 nM); cdk5-p35 (IC50 = 75 nM); erk1 (IC50 = 9000 nM)
Purvalanol A (NG60) is a specific inhibitor of cyclin-dependent kinases (CDKs) with the following IC50 values in enzyme assays : - CDK1/cyclin B: 4 nM - CDK2/cyclin E: 35 nM - CDK2/cyclin A: 70 nM - CDK4/cyclin D1: 850 nM - CDK5/p35: 75 nM |
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| ln Vitro |
Purvalanol A has IC50s of 80 and 9000 nM for inhibiting cdc28 (S. cerevisiae) and erk1. Purvalanol A exhibits inhibitory activities against the NCI panel of 60 human tumor cell lines, with an average GI50 of 2 μM. Two cell lines, the NCI-H522 non-small cell lung cancer cell line with a GI50 of 347 nM and the KM12 colon cancer cell line with a GI50 of 76 nM, exhibit a -20-fold increase in sensitivity to purvalanol A[1]. In addition to being a 2.5-fold more potent inhibitor of CDK2, purvalanol A also exhibits potent low-micromolar inhibitory effects on DYRK1A and several other protein kinases. Purvalanol A inhibits JNK/SAPK1c, MKK1, MAPK2/ERK2, and has IC50 values of 80, 26, and 84 μM[2]. The phosphorylation of cellular proteins is specifically inhibited by purvalanol A. When the G1 phase is induced by serum, purvalanol A stops the contents of cyclins D and E from increasing. In cell-free environments, purvalanol A does not impede transcription[3].
- In synchronized human cancer cells (e.g., HCT116 colon cancer cells), Purvalanol A induced reversible G1 and G2 cell cycle arrest, preventing progression through the S phase. It selectively inhibited phosphorylation of CDK substrates such as retinoblastoma protein (Rb) and cyclin E, reduced cellular levels of cyclins D1 and E, and increased the expression of the CDK inhibitor p21WAF1/CIP1 [3]. - In exponentially growing cells treated with Purvalanol A for 24 hours, sustained proliferation inhibition and cell death were observed, with higher sensitivity in transformed cell lines. It showed antiproliferative activity against various human tumor cell lines, with an average GI₅₀ of 2 μM, and enhanced sensitivity in specific lines like KM12 colon cancer cells (GI₅₀ = 76 nM) [3]. - The compound did not affect general transcription in cell-free systems but inhibited estrogen-induced luciferase reporter gene expression in transfected cells, indicating involvement in specific transcriptional regulation mediated by CDKs [3]. |
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| ln Vivo |
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| Enzyme Assay |
Purvalanol A is a potent CDK inhibitor, inhibiting cdc2-cyclin B, cdk2-cyclin A, cdk2-cyclin E, cdk4-cyclin D1, and cdk5-p35 with IC50s of 4, 70, 35, 850, 75 nM, resepctively.
- CDK Kinase Activity Assay: Recombinant CDK-cyclin complexes (e.g., CDK2/cyclin E, CDK1/cyclin B) were incubated with Purvalanol A (concentration range: 0.01–1000 nM) and radiolabeled ATP, using histone H1 or specific peptide substrates. Phosphorylation levels were detected by autoradiography after SDS-PAGE separation, and IC₅₀ values were calculated based on inhibition curves. This method was used to determine the specificity of Purvalanol A for different CDK isoforms [1] |
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| Cell Assay |
- Cell Cycle Analysis: Cells were synchronized using double thymidine block, then released into medium containing Purvalanol A (0.1–10 μM). At different time points, cells were harvested, fixed in ethanol, stained with propidium iodide, and analyzed by flow cytometry to determine the distribution of cells in G1, S, and G2 phases. Western blot analysis confirmed reduced phosphorylation of Rb and cyclin E, as well as increased p21WAF1/CIP1 expression [3].
- Antiproliferative Activity Assay: Exponentially growing tumor cells were treated with Purvalanol A (0.01–10 μM) for 24 hours. Cell viability was measured by MTT assay, showing dose-dependent inhibition, with significant effects observed at concentrations ≥0.5 μM [3]. In 96-well plates, cells are seeded at a density of 10,000 and exposed to different concentrations of Purvalanol A (0-100 μM) for a duration of 24 hours. For four hours, cells are incubated at 37°C after being exposed to 10 μL of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide dye (5 mg/mL). 100 μL of DMSO is added to the formazan crystals to help them dissolve. The absorbance is measured spectrophotometrically at 570 nm. |
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| Animal Protocol |
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| References |
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| Additional Infomation |
Purvalanol A is a purvalanol.
- Purvalanol A exerts its effects by competitively binding to the ATP-binding site of CDKs, disrupting kinase-substrate interactions and downstream signaling pathways critical for cell cycle regulation [1]
- Its cell death-inducing effect is proliferation-dependent; quiescent fibroblasts can resume cell cycle activity after drug removal, indicating reversible inhibition [3]. - The compound's specificity for CDKs makes it a valuable tool for studying CDK-mediated cellular processes, particularly cell cycle progression and transcriptional regulation [2] |
| Molecular Formula |
C19H25CLN6O
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| Molecular Weight |
388.89
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| Exact Mass |
388.177
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| Elemental Analysis |
C, 58.68; H, 6.48; Cl, 9.12; N, 21.61; O, 4.11
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| CAS # |
212844-53-6
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| Related CAS # |
Purvalanol B;212844-54-7
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| PubChem CID |
456214
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| Appearance |
Grey to green solid powder
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| Density |
1.3±0.1 g/cm3
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| Boiling Point |
590.5±60.0 °C at 760 mmHg
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| Flash Point |
310.9±32.9 °C
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| Vapour Pressure |
0.0±1.7 mmHg at 25°C
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| Index of Refraction |
1.654
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| LogP |
2.77
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
7
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| Heavy Atom Count |
27
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| Complexity |
468
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| Defined Atom Stereocenter Count |
1
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| SMILES |
ClC1=C([H])C([H])=C([H])C(=C1[H])N([H])C1=C2C(=NC(=N1)N([H])[C@@]([H])(C([H])([H])O[H])C([H])(C([H])([H])[H])C([H])([H])[H])N(C([H])=N2)C([H])(C([H])([H])[H])C([H])([H])[H]
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| InChi Key |
PMXCMJLOPOFPBT-HNNXBMFYSA-N
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| InChi Code |
InChI=1S/C19H25ClN6O/c1-11(2)15(9-27)23-19-24-17(22-14-7-5-6-13(20)8-14)16-18(25-19)26(10-21-16)12(3)4/h5-8,10-12,15,27H,9H2,1-4H3,(H2,22,23,24,25)/t15-/m0/s1
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| Chemical Name |
(2R)-2-[[6-(3-chloroanilino)-9-propan-2-ylpurin-2-yl]amino]-3-methylbutan-1-ol
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| Synonyms |
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (6.43 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (6.43 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.5714 mL | 12.8571 mL | 25.7142 mL | |
| 5 mM | 0.5143 mL | 2.5714 mL | 5.1428 mL | |
| 10 mM | 0.2571 mL | 1.2857 mL | 2.5714 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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