 Chemical Structure.png)
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).
Physicochemical Properties
| Molecular Formula | C19H25CLN6O | |
| Molecular Weight | 388.89 | |
| Exact Mass | 388.177 | |
| Elemental Analysis | C, 58.68; H, 6.48; Cl, 9.12; N, 21.61; O, 4.11 | |
| CAS # | 212844-53-6 | |
| Related CAS # | Purvalanol B;212844-54-7 | |
| PubChem CID | 456214 | |
| Appearance | Grey to green solid powder | |
| Density | 1.3±0.1 g/cm3 | |
| Boiling Point | 590.5±60.0 °C at 760 mmHg | |
| Flash Point | 310.9±32.9 °C | |
| Vapour Pressure | 0.0±1.7 mmHg at 25°C | |
| Index of Refraction | 1.654 | |
| LogP | 2.77 | |
| Hydrogen Bond Donor Count | 3 | |
| Hydrogen Bond Acceptor Count | 6 | |
| Rotatable Bond Count | 7 | |
| Heavy Atom Count | 27 | |
| Complexity | 468 | |
| Defined Atom Stereocenter Count | 1 | |
| 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] |
|
| InChi Key | PMXCMJLOPOFPBT-HNNXBMFYSA-N | |
| 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 | |
| Chemical Name | (2R)-2-[[6-(3-chloroanilino)-9-propan-2-ylpurin-2-yl]amino]-3-methylbutan-1-ol | |
| Synonyms |
|
|
| HS Tariff Code | 2934.99.9001 | |
| Storage |
Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
|
| Shipping Condition | Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs) |
Biological Activity
| 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) | ||
| ln Vitro |
|
||
| ln Vivo |
|
||
| 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. | ||
| Cell Assay | 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. | ||
| Animal Protocol |
|
||
| References |
[1]. Exploiting chemical libraries, structure, and genomics in the search for kinase inhibitors. Science. 1998 Jul 24;281(5376):533-8. [2]. The specificities of protein kinase inhibitors: an update. Biochem J. 2003 Apr 1;371(Pt 1):199-204. [3]. Cellular effects of purvalanol A: a specific inhibitor of cyclin-dependent kinase activities. Int J Cancer. 2002 Feb 20;97(6):761-9. |
||
| Additional Infomation | Purvalanol A is a purvalanol. |
Solubility Data
| Solubility (In Vitro) |
|
|||
| 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 |