Cyclin-Dependent Kinases (Cdk) as Targets for Cancer Therapy and Imaging

Graf, Franziska; Wuest, Frank; Pietzsch, Jens

doi:10.5772/24852

Cited by 4 publications

(3 citation statements)

References 121 publications

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“…And, a study published in [ 29 ] said that the drug of Nutlin-3 is a tumor suppresser, which can up-regulate the expression of Notch1 in both lymphoid and myeloid leukemic cells. And we discover that PD-0332991 is a CDK 4/6 inhibitor [ 30 ] and can act on chronic myeloid leukemia [ 31 ]. In Table 1 , LBW242 is associated with Chronic myeloid leukemia pathway, but their association is not validated in the CancerResource.…”

Section: Resultsmentioning

confidence: 99%

Identifying drug-pathway association pairs based on L2,1-integrative penalized matrix decomposition

et al. 2017

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BackgroundTraditional drug identification methods follow the “one drug-one target” thought. But those methods ignore the natural characters of human diseases. To overcome this limitation, many identification methods of drug-pathway association pairs have been developed, such as the integrative penalized matrix decomposition (iPaD) method. The iPaD method imposes the L1-norm penalty on the regularization term. However, lasso-type penalties have an obvious disadvantage, that is, the sparsity produced by them is too dispersive.ResultsTherefore, to improve the performance of the iPaD method, we propose a novel method named L2,1-iPaD to identify paired drug-pathway associations. In the L2,1-iPaD model, we use the L2,1-norm penalty to replace the L1-norm penalty since the L2,1-norm penalty can produce row sparsity.ConclusionsBy applying the L2,1-iPaD method to the CCLE and NCI-60 datasets, we demonstrate that the performance of L2,1-iPaD method is superior to existing methods. And the proposed method can achieve better enrichment in terms of discovering validated drug-pathway association pairs than the iPaD method by performing permutation test. The results on the two real datasets prove that our method is effective.

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Section: Resultsmentioning

confidence: 99%

Identifying drug-pathway association pairs based on L2,1-integrative penalized matrix decomposition

et al. 2017

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“…In this study, significant inhibition of CDK6 was observed in cancer cell lines targeted with C-glycosyl flavone. Targeting CDK6 by flavopiridol, a flavonoid derivative, was reported in cancer cell lines 26 . Earlier, Cover et al 27 reported that inhibition of CDK6 activity closely related to the reduction of cell proliferation in human breast cancer cells.…”

Section: Discussionmentioning

confidence: 99%

C-glycosyl flavone from Urginea indica inhibits proliferation & angiogenesis & induces apoptosis via cyclin-dependent kinase 6 in human breast, hepatic & colon cancer cell lines

Bevara¹,

Kumar²,

Koteshwaramma³

et al. 2018

Indian Journal of Medical Research

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Background & objectives:Search for novel compounds beneficial to the treatment of cancer attracts a great deal of attention. We earlier demonstrated the isolation of 5,7-dihydroxy-2-[4’-hydroxy-3’-(methoxymethyl)phenyl]-6-C-β-glucopyranosyl flavone, a novel C-glycosyl flavone from Urginea indica bulb. The present study was undertaken to investigate the effect of this novel compound on human normal epithelial and breast, hepatic and colon cancer cell lines.Methods:The maximum non-toxic concentration (MNTC) and cytotoxicity of C-glycosyl flavone were assayed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT). Cell cycle was analyzed by flow cytometry. Docking studies were performed to predict possible targets. Levels of cyclin-dependent kinase 1 (CDK1) and CDK6, Bcl2 and BAX and cytochrome c were quantified by specific ELISA. Mitochondrial membrane potential was determined using JC-1 dye. Apoptosis was quantified by Annexin V ELISA method.Results:Flow cytometry analysis demonstrated G0/G1 arrest. In silico docking studies predicted CDK1 and CDK6 as a possible target of C-glycosyl flavone. In vitro study confirmed CDK6 as the main target in C-glycosyl flavone-treated cancer cell lines. C-glycosyl flavone treatment also induced membrane blebbing, chromatin fragmentation and nucleosome formation. C-glycosyl flavone treatment caused marked loss of mitochondrial membrane potential, decrease in Bcl2/BAX ratio and activation of caspase-3 and release of caspase-9 and cytochrome c. In addition, C-glycosyl flavone inhibited the tumour-induced angiogenesis and reduced the vascular endothelial growth factor levels. Similarly, CDK6 inhibitor significantly inhibited proliferation and angiogenesis and induced apoptosis in tested cell lines.Interpretation & conclusions:The results indicate that C-glycosyl flavone may exert induction of apoptosis, cell cycle arrest and inhibition of angiogenesis via CDK6. Thus, targeting CDK6 using C-glycosyl flavone may serve as a novel therapeutic approach for the treatment of breast, hepatic and colon cancers.

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“…used 1‐(3‐[ 18 F]fluoropropyl)piperazines as model compounds to prepare 18 F‐radiotracers based on inhibitors to image cyclin‐dependent kinases (CDK), [73] since the piperazine moiety is a basic structural element of these CDK‐inhibitors (Scheme 16 ). [74] They started with 1‐(4‐nitrophenyl)piperazine 53 a and 1‐(6‐nitropyridin‐3‐yl)piperazine 53 b , respectively, which were treated with 3‐bromopropanol to introduce the 3‐hydroxypropyl chain. After tosylation of the alcohol functions of 54 a , b , the open‐chain derivatives 55 a , b were obtained, which tend to cyclise spontaneously to the spiro salts 56 a , b even at room temperature and much better in polar solvents like DMSO.…”

Section: Azetidinium Saltsmentioning

confidence: 99%

Strained Ammonium Precursors for Radiofluorinations

Reissig

Mamat

2022

ChemistryOpen

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The increasing application of positron emission tomography (PET) in nuclear medicine has stimulated the extensive development of a multitude of novel and versatile techniques to introduce fluorine-18, especially for the radiolabelling of biologically or pharmacologically active molecules. Taking into consideration that the introduction of fluorine-18 (t 1/2 = 109.8 min) mostly proceeds under harsh conditions, radiolabelling of such molecules represents a challenge and is of enormous interest. Ideally, it should proceed in a regioselective manner under mild physiological conditions, in an acceptable time span, with high yields and high specific activities. Special attention has been drawn to 2-fluoroethyl and 3-fluoropropyl groups, which are often the active sites of radiofluorinated compounds. Precursors containing an ammonium leaving group -such as a strained azetidinium or aziridinium moietycan help to overcome these obstacles leading to a convenient and mild introduction of [ 18 F]fluoride with high radiochemical yields.

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Cyclin-Dependent Kinases (Cdk) as Targets for Cancer Therapy and Imaging

Cited by 4 publications

References 121 publications

Identifying drug-pathway association pairs based on L2,1-integrative penalized matrix decomposition

Identifying drug-pathway association pairs based on L2,1-integrative penalized matrix decomposition

C-glycosyl flavone from Urginea indica inhibits proliferation & angiogenesis & induces apoptosis via cyclin-dependent kinase 6 in human breast, hepatic & colon cancer cell lines

Strained Ammonium Precursors for Radiofluorinations

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