Disease relevance of PURVALANOL

• In particular, Purvalanol A, with an IC50 of 0.035 microm inhibits activated, but not basal transcription, as well as HTLV-1 infected cells [1].

High impact information on PURVALANOL

• Here we find that three CDKIs, flavopiridol, purvalanol A, and methoxy-roscovitine, block Moloney murine leukemia virus (MLV) transcription events [2].
• The cdc25 phosphatase inhibitors (Cpd 5 and NSC 663284) and the cdc2 kinase inhibitors (alsterpaullone and purvalanol A) enhanced SNP-induced cytotoxicity and the decrease in survivin expression [3].
• Inhibition of p34(cdc2) activity by purvalanol A caused mitotic-arrested cells to rapidly exit mitosis, suggesting that sustained p34(cdc2) activity was responsible for metaphase arrest [4].
• Cotreatment with a histone deacetylase inhibitor (an indirect inhibitor of cdk activity), purvalanol A and roscovitine (direct cdk inhibitors), and the reduction of cyclin B expression using RNA interference decreased the hyperphosphorylation of 4E-BP1 in PTX treated cells [5].
• Furthermore, purvalanol inhibited the nuclear accumulation of p42/p44 MAPK, an event dependent on the catalytic activity of these kinases [6].

Biological context of PURVALANOL

• We have studied the effects of purvalanol A on the cell cycle progression, proliferation and viability [7].
• When exponentially growing cells, both mouse fibroblasts and human cancer cell lines, were incubated with purvalanol A for prolonged periods of time (24 hr), a lasting inhibition of cell proliferation as well as cell death were observed [7].
• Furthermore, no up-regulation of cdc2 protein was observed when paclitaxel-treated cells were prevented from entering mitosis by treatment with purvalanol A, a cyclin-dependent kinase (CDK) inhibitor, or stimulated to exit mitosis with 2-AP, a non-specific kinase inhibitor [8].
• In synchronized cells, purvalanol A induced a reversible arrest the progression in G1 and G2 phase of the cell cycle, but did not prevent the completion of DNA synthesis in S-phase cells [7].
• Moreover, phosphorylation of Rb and neuronal cell death provoked by p27 siRNA were abrogated by pharmacological CDK inhibitors, olomoucine and purvalanol A [9].

Anatomical context of PURVALANOL

• The Chinese hamster lung fibroblast cell line CCL39 was used as a model to investigate the anti-proliferative properties of purvalanol [6].
• However, a higher dose of purvalanol A i.e. 40 nmol/3 microl given 2.5 h before BrdU administration significantly decreased the number of BrdU-positive nuclei in the DG of the hippocampus (by approximately 35%) [10].
• Purvalanol A, a selective inhibitor of CDKs, was injected into the brain lateral ventricle at concentrations of 4 nmol/3 microl or 40 nmol/3 microl [10].

Associations of PURVALANOL with other chemical compounds

• Cycloheximide block-and-release experiments clearly demonstrated that even in the presence of enough amounts of the BZLF1 protein, purvalanol A blocked expression of lytic viral proteins at transcription level [11].

Gene context of PURVALANOL

• In contrast to purvalanol B binding in CDK2, purvalanol A binds in c-Src with a conformational change in a more open ATP pocket [12].
• Cellular effects of purvalanol A: a specific inhibitor of cyclin-dependent kinase activities [7].
• When cells were treated with purvalanol, p42/p44 MAPK and CDK1 activities were inhibited in a dose-dependent manner [6].
• p42/p44 MAPKs are intracellular targets of the CDK inhibitor purvalanol [6].
• RESULTS: To address this issue, purvalanol B (95. ) and an N6-methylated, CDK-inactive derivative (95M. ) were immobilized on an agarose matrix [13].

Analytical, diagnostic and therapeutic context of PURVALANOL

• In this technique, cell extracts were screened for purvalanol-interacting proteins by affinity chromatography on immobilized inhibitor [6].

References