WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#: 406332
CAS#: 212844-53-6
Description: Purvalanol A is a potent CDK inhibitor, which effectively suppresses Src-mediated transformation by inhibiting both CDKs and c-Src. indicating that the activation of CDKs contributes to the c-Src transformation. Purvalanol A suppressed the c-Src activity as effectively as the Src-selective inhibitor PP2, and that it reverted the transformed morphology to a nearly normal shape with less cytotoxicity than PP2. Purvalanol A induced a strong G2-M arrest, whereas PP2 weakly acted on the G1-S transition. Furthermore, when compared with PP2, purvalanol A more effectively suppressed the growth of human colon cancer HT29 and SW480 cells, in which Src family kinases and CDKs are activated.
MedKoo Cat#: 406332
Name: Purvalanol A
CAS#: 212844-53-6
Chemical Formula: C19H25ClN6O
Exact Mass: 388.17784
Molecular Weight: 388.89
Elemental Analysis: C, 58.68; H, 6.48; Cl, 9.12; N, 21.61; O, 4.11
Synonym: Purvalanol A, Purv; NG60; NG-60; NG 60.
IUPAC/Chemical Name: (R)-2-((6-((3-chlorophenyl)amino)-9-isopropyl-9H-purin-2-yl)amino)-3-methylbutan-1-ol
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
SMILES Code: CC(C)[C@@H](NC1=NC(NC2=CC=CC(Cl)=C2)=C3N=CN(C(C)C)C3=N1)CO
Appearance: Grey to green solid powder
Purity: >98% (or refer to the Certificate of Analysis)
Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs
Storage Condition: 0 – 4 oC for short term (weeks to 1 month) or -20 oC for long terms (months to years).
Solubility: Soluble in DMSO
Shelf Life: >2 years if stored properly.
Drug Formulation: This drug may be formulated in DMSO
Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code: 2934.99.9001
| Biological target: | Purvalanol A is a CDK 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, resepctively. |
| In vitro activity: | The present study has made the novel discovery that the CDK‐2 inhibitor, purvalanol A, triggers a rapid onset of apoptosis in human neutrophils, but not in PBMCs. This inhibitor induces a rapid loss of Mcl‐1 protein, but this inhibitor had no effect on Mcl‐1 mRNA levels (measured by qPCR) during a 4‐h incubation compared to untreated control levels. This rapid loss in Mcl‐1 protein levels was found to be due to an increase in the turnover rate of the protein that was induced by purvalanol A, the half‐life of the protein being decreased from approximately 2 h to approximately 1 h. Unlike PBMCs, which also express the anti‐apoptotic proteins, Bcl‐2 and Bcl‐XL, this loss of Mcl‐1 induced by purvalanol A induced rapid cell death in neutrophils because of their high dependency upon this protein for survival. Reference: Clin Exp Immunol. 2018 May; 192(2): 171–180. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5904697/ |
| In vivo activity: | However, purvalanol A had a significant effect on the number of BrdU nuclei [F(2, 15) = 11.36; p < 0.001], if it was given 2.5 h before BrdU administration. Post hoc Duncan’s test revealed that a higher concentration of purvalanol A (40 nmol/3 µl) significantly decreased the number of BrdU-positive nuclei in the DG of the rat hippocampus (by approximately 35%, p < 0.005) (Fig. 1, 2) while a lower concentration of the CDKs inhibitor (4 nmol/3 µl) did not affect the number of BrdU-positive cells in the DG (p < 0.98) (Fig. 1). The present study indicates that purvalanol A inhibited the cell proliferation in the DG of the hippocampus, since a decrease in the number of BrdU-positive cells after purvalanol A treatment has been observed. Reference: Pharmacol Rep. 2005 Nov-Dec;57(6):845-9. https://pubmed.ncbi.nlm.nih.gov/16382206/ |
| Solvent | Max Conc. mg/mL | Max Conc. mM | |
|---|---|---|---|
| Solubility | |||
| DMSO | 30.0 | 77.1 | |
| Ethanol | 10.0 | 25.7 |
The following data is based on the product molecular weight 388.89 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass | 1 mg | 5 mg | 10 mg |
|---|---|---|---|
| 1 mM | 1.15 mL | 5.76 mL | 11.51 mL |
| 5 mM | 0.23 mL | 1.15 mL | 2.3 mL |
| 10 mM | 0.12 mL | 0.58 mL | 1.15 mL |
| 50 mM | 0.02 mL | 0.12 mL | 0.23 mL |
| Formulation protocol: | 1. Phoomvuthisarn P, Cross A, Glennon-Alty L, Wright HL, Edwards SW. The CDK inhibitor purvalanol A induces neutrophil apoptosis and increases the turnover rate of Mcl-1: potential role of p38-MAPK in regulation of Mcl-1 turnover. Clin Exp Immunol. 2018 May;192(2):171-180. doi: 10.1111/cei.13107. Epub 2018 Mar 9. PMID: 29377076; PMCID: PMC5904697. 2. Hikita T, Oneyama C, Okada M. Purvalanol A, a CDK inhibitor, effectively suppresses Src-mediated transformation by inhibiting both CDKs and c-Src. Genes Cells. 2010 Oct;15(10):1051-62. doi: 10.1111/j.1365-2443.2010.01439.x. Epub 2010 Sep 5. PMID: 20825494. 3. Maćkowiak M, Kolasiewicz W, Markowicz-Kula K, Wedzony K. Purvalanol A, inhibitor of cyclin-dependent kinases attenuates proliferation of cells in the dentate gyrus of the adult rat hippocampus. Pharmacol Rep. 2005 Nov-Dec;57(6):845-9. PMID: 16382206. |
| In vitro protocol: | 1. Phoomvuthisarn P, Cross A, Glennon-Alty L, Wright HL, Edwards SW. The CDK inhibitor purvalanol A induces neutrophil apoptosis and increases the turnover rate of Mcl-1: potential role of p38-MAPK in regulation of Mcl-1 turnover. Clin Exp Immunol. 2018 May;192(2):171-180. doi: 10.1111/cei.13107. Epub 2018 Mar 9. PMID: 29377076; PMCID: PMC5904697. 2. Hikita T, Oneyama C, Okada M. Purvalanol A, a CDK inhibitor, effectively suppresses Src-mediated transformation by inhibiting both CDKs and c-Src. Genes Cells. 2010 Oct;15(10):1051-62. doi: 10.1111/j.1365-2443.2010.01439.x. Epub 2010 Sep 5. PMID: 20825494. |
| In vivo protocol: | 1. Maćkowiak M, Kolasiewicz W, Markowicz-Kula K, Wedzony K. Purvalanol A, inhibitor of cyclin-dependent kinases attenuates proliferation of cells in the dentate gyrus of the adult rat hippocampus. Pharmacol Rep. 2005 Nov-Dec;57(6):845-9. PMID: 16382206. |
1: Obakan P, Arısan ED, Ozfiliz P, Coker-Gürkan A, Palavan-Ãœnsal N. Purvalanol A is a strong apoptotic inducer via activating polyamine catabolic pathway in MCF-7 estrogen receptor positive breast cancer cells. Mol Biol Rep. 2013 Nov 5. [Epub ahead of print] PubMed PMID: 24190492.
2: Hofman J, Kučera R, Cihalova D, Klimes J, Ceckova M, Staud F. Olomoucine II, but Not Purvalanol A, Is Transported by Breast Cancer Resistance Protein (ABCG2) and P-Glycoprotein (ABCB1). PLoS One. 2013 Oct 8;8(10):e75520. doi: 10.1371/journal.pone.0075520. PubMed PMID: 24116053; PubMed Central PMCID: PMC3792958.
3: Hofman J, Ahmadimoghaddam D, Hahnova L, Pavek P, Ceckova M, Staud F. Olomoucine II and purvalanol A inhibit ABCG2 transporter in vitro and in situ and synergistically potentiate cytostatic effect of mitoxantrone. Pharmacol Res. 2012 Mar;65(3):312-9. doi: 10.1016/j.phrs.2011.11.017. Epub 2011 Dec 6. PubMed PMID: 22173067.
4: Hikita T, Oneyama C, Okada M. Purvalanol A, a CDK inhibitor, effectively suppresses Src-mediated transformation by inhibiting both CDKs and c-Src. Genes Cells. 2010 Oct;15(10):1051-62. doi: 10.1111/j.1365-2443.2010.01439.x. Epub 2010 Sep 5. PubMed PMID: 20825494.
5: Agbottah E, Yeh WI, Berro R, Klase Z, Pedati C, Kehn-Hall K, Wu W, Kashanchi F. Two specific drugs, BMS-345541 and purvalanol A induce apoptosis of HTLV-1 infected cells through inhibition of the NF-kappaB and cell cycle pathways. AIDS Res Ther. 2008 Jun 10;5:12. doi: 10.1186/1742-6405-5-12. PubMed PMID: 18544167; PubMed Central PMCID: PMC2483717.
6: Iizuka D, Ogura A, Kuwabara M, Inanami O. Purvalanol A induces apoptosis and downregulation of antiapoptotic proteins through abrogation of phosphorylation of JAK2/STAT3 and RNA polymerase II. Anticancer Drugs. 2008 Jul;19(6):565-72. doi: 10.1097/CAD.0b013e3282fe330e. PubMed PMID: 18525315.
7: Iizuka D, Inanami O, Kashiwakura I, Kuwabara M. Purvalanol A enhances cell killing by inhibiting up-regulation of CDC2 kinase activity in tumor cells irradiated with high doses of X rays. Radiat Res. 2007 May;167(5):563-71. PubMed PMID: 17474786.
8: Maćkowiak M, Kolasiewicz W, Markowicz-Kula K, Wedzony K. Purvalanol A, inhibitor of cyclin-dependent kinases attenuates proliferation of cells in the dentate gyrus of the adult rat hippocampus. Pharmacol Rep. 2005 Nov-Dec;57(6):845-9. PubMed PMID: 16382206.
9: Villerbu N, Gaben AM, Redeuilh G, Mester J. Cellular effects of purvalanol A: a specific inhibitor of cyclin-dependent kinase activities. Int J Cancer. 2002 Feb 20;97(6):761-9. PubMed PMID: 11857351.
