Targets for cancer therapy in the cell cycle pathway

Rn, Rao

doi:10.1097/00001622-199611000-00012

Cited by 31 publications

(16 citation statements)

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“…Cyclin-dependent kinases (CDKs) have been characterised extensively in the past two decades. CDKs are serine/threonine kinases that play a crucial role in the regulation of the cell division cycle processes, apoptosis, transcription and differentiation [7,8]. Thus far, family members of this class have been identified to include over nine CDKs.…”

Section: Introductionmentioning

confidence: 99%

De novodesign of quinazoline derivatives as CDK2 inhibitors: 3D-QSAR, molecular fragment replacement and Volsurf predictions

Wang¹,

Chen²,

Liu³

et al. 2011

Molecular Simulation

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Cyclin-dependent kinase 2 (CDK2) has appeared as an important drug target over the years with a multitude of therapeutic potentials. To design compounds with enhanced inhibitory potencies against CDK2, 3D-QSAR and molecular fragment replacement studies were performed on the pyrazolo[4,3-h ]quinazoline derivatives, a class of potent CDK2 inhibitors. The contours of 3D-QSAR model revealed important structural features of the inhibitors related to the active site of CDK2. Based on the pyrazolo[4,3-h ]quinazoline core, the different substituents at three important points were replaced with diverse molecular fragments. The compounds resulting from fragments assembly with pyrazolo[4,3-h ]quinazoline core were then scored with the robust 3D-QSAR model. Furthermore, the absorption, distribution, metabolism and excretion properties of these compounds were predicted by Volsurf to eliminate inappropriate compounds. Thirty-one new potential compounds were finally obtained. These results initiated us to further optimise and design new potential inhibitors.

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Section: Introductionmentioning

confidence: 99%

De novodesign of quinazoline derivatives as CDK2 inhibitors: 3D-QSAR, molecular fragment replacement and Volsurf predictions

Wang¹,

Chen²,

Liu³

et al. 2011

Molecular Simulation

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“…Dysregulation of cell cycle components may cause the cell to multiply uncontrollably, thus leading to tumor formation (Champeris Tsaniras et al, 2014), as is the case for GBM (Hazane-Puch et al, 2015;Xie et al, 2015). Various studies have shown that the cell cycle pathway and cell cycle-related molecules can be considered therapeutic targets of many cancers (Rao, 1996;Newman et al, 2002). Di Tomaso et al (2000) found that the uncontrolled proliferation of glioma cells may be linked to genetic alterations in the cell cycle pathway.…”

Section: Discussionmentioning

confidence: 99%

Dysregulation of TFDP1 and of the cell cycle pathway in high-grade glioblastoma multiforme: a bioinformatic analysis

Lü¹,

Lv²,

Yh³

et al. 2016

Genet. Mol. Res.

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ABSTRACT. Despite extensive research, the prognosis of high-grade glioblastoma multiforme (GBM) has improved only slightly because of the limited response to standard treatments. Recent advances (discoveries of molecular biomarkers) provide new opportunities for the treatment of GBM. The aim of the present study was to identify diagnostic biomarkers of high-grade GBM. First, we combined 3 microarray expression datasets to screen them for genes differentially expressed in patients with high-grade GBM relative to healthy subjects. Next, the target network was constructed via the empirical Bayesian coexpression approach, and centrality analysis and a molecular complex detection (MCODE) algorithm were performed to explore hub genes and functional modules. Finally, a validation test was conducted to verify the bioinformatic results. A total of 277 differentially expressed genes were identified according to the criteria P < 0.05 and |log 2 (fold change)| ≥ 1.5. These genes were most significantly enriched in the cell cycle pathway. Centrality analysis uncovered 9 hub genes; among them, TFDP1 showed the highest degree of connectivity (43) and is a known participant in the cell cycle pathway; this finding pointed to the important role of TFDP1 in the progression of high-grade GBM. Experimental validation mostly supported the bioinformatic results. According to our study results, the gene TFDP1 and the cell cycle pathway are strongly associated with high-grade GBM; this result may provide new insights into the pathogenesis of GBM.

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“…Thus, olomoucine (70), a purine derivative, was shown to be a specific inhibitor of cdc2, cdk1, cdk2, and cdk5, resulting in inhibition of the G1 to S1 phase transitions of a number of human cancer cell lines [258,259,263,274,275]. The adenine moiety of 70 binds in the same pocket as the adenine of ATP but with a different orientation of the purine ring while the N6-benzyl group of 70 binds outside the ATP-binding pocket and probably contributes to its specificity [276].…”

Section: Cell Cycle Regulation and Control Of Cancer Growthmentioning

confidence: 99%

“…An inhibition cdk4 and cdk6 was attributed to this activity [278]. Another approach to cell cycle control is the inhibition of phosphatases in the cell cycle which can shift the balance toward an inhibitory phosphorylation and, thus, prevent the activation of the cdks that promote movements through the cycle [262,263]. Thus, the overexpression of the cell cycle phosphatase cdc25 was found in some primary cancers, such as breast and lung cancers [279].…”

Section: Cell Cycle Regulation and Control Of Cancer Growthmentioning

confidence: 99%

“…The cdk inhibitors can act as cytostatic and cytotoxic agents, and can increase the anticancer activity of cytotoxic agents by inducing cancer cells to either arrest or delay progress through those cell cycle phases in which they are more sensitive to the cytotoxic drug [263]. The cdk inhibitors and cell cycle inhibitors can also protect cells from cytotoxic activity by preventing cells from progression through the cell cycle.…”

Section: Cell Cycle Regulation and Control Of Cancer Growthmentioning

confidence: 99%

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Critical appraisals of approaches for predictive designs in anticancer drugs

Gnewuch

Sosnovsky

2002

Cellular and Molecular Life Sciences (CMLS)

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The present review provides a critical appraisal of the most important areas in cancer drug research and, ultimately, in clinical oncology and therapy, with emphasis on the elucidation of possible predictive designs for the development of new anticancer drugs. These assessments encompass the well-established anticancer drugs and congeners which have been employed over the years in clinical therapy, and the more recent exploratory agents still requiring further rigorous scrutiny in the clinical environment. These areas mainly include the bioreversible redox carriers, the boron neutron capture compounds, some new mitosis-interactive agents, cell cycle modifiers, biological-response mpdifiers, oncogene inhibitors, drug-antibody conjugates, cancer cell suppression and destruction agents, antiangiogenesis and antimetastasis agents, apoptosis-promoting agents, and gene therapy and vaccines.

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Targets for cancer therapy in the cell cycle pathway

Cited by 31 publications

References 0 publications

De novodesign of quinazoline derivatives as CDK2 inhibitors: 3D-QSAR, molecular fragment replacement and Volsurf predictions

De novodesign of quinazoline derivatives as CDK2 inhibitors: 3D-QSAR, molecular fragment replacement and Volsurf predictions

Dysregulation of TFDP1 and of the cell cycle pathway in high-grade glioblastoma multiforme: a bioinformatic analysis

Critical appraisals of approaches for predictive designs in anticancer drugs

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