Browse
Submit Data
Databases
API
Help

Dataset Information

25 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Structural insights into G-quadruplexes: towards new anticancer drugs.

ABSTRACT: DNA G-quadruplexes are DNA secondary structures formed in specific G-rich sequences. DNA sequences that can form G-quadruplexes have been found in regions with biological significance, such as human telomeres and oncogene-promoter regions. DNA G-quadruplexes have recently emerged as a new class of novel molecular targets for anticancer drugs. Recent progress on structural studies of the biologically relevant G-quadruplexes formed in human telomeres and in the promoter regions of human oncogenes will be discussed, as well as recent advances in the design and development of G-quadruplex-interactive drugs. DNA G-quadruplexes can readily form in solution under physiological conditions and are globularly folded nucleic acid structures. The molecular structures of intramolecular G-quadruplexes appear to differ from one another and, therefore, in principle may be differentially regulated and targeted by different proteins and drugs.

SUBMITTER: Yang D

PROVIDER: S-EPMC2886307 | biostudies-literature | 2010 Apr

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Structural insights into G-quadruplexes: towards new anticancer drugs.

Yang Danzhou D Okamoto Keika K

Future medicinal chemistry 20100401 4

DNA G-quadruplexes are DNA secondary structures formed in specific G-rich sequences. DNA sequences that can form G-quadruplexes have been found in regions with biological significance, such as human telomeres and oncogene-promoter regions. DNA G-quadruplexes have recently emerged as a new class of novel molecular targets for anticancer drugs. Recent progress on structural studies of the biologically relevant G-quadruplexes formed in human telomeres and in the promoter regions of human oncogenes ...[more]

PMID: 20563318

Similar Datasets

Buckysomes: New Nanocarriers for Anticancer Drugs.

Project description:Buckysomes, liposome-like vesicles comprised of dendritic C60 subunits that self-assemble into unilamellar vesicles, are unique nanovectors that have utility in drug delivery. We have prepared paclitaxel-embedded buckysomes (PEBs) and examined biodistriubition profiles with commercially available formulations of the drug. As compared to Abraxane, an albumin-bound formulation of paclitaxel, PEBs showed higher tissue accumulation in the liver and the kidney at 45 and 60 minutes and in the lungs at 30 minutes, making them suitable drug-delivery carriers for short-term therapy to the mentioned organs. These buckysomes can be further functionalized to specifically deliver paclitaxel to the tumor site.

| S-EPMC4600851 | biostudies-literature

NSAIDs: Old Drugs Reveal New Anticancer Targets.

Project description:There is compelling evidence that nonsteroidal anti-inflammatory drugs (NSAIDs) and cyclooxygenase-2 selective inhibitors have antineoplastic activity, but toxicity from cyclooxygenase (COX) inhibition and the suppression of physiologically important prostaglandins limits their use for cancer chemoprevention. Previous studies as reviewed here suggest that the mechanism for their anticancer properties does not require COX inhibition, but instead involves an off-target effect. In support of this possibility, recent molecular modeling studies have shown that the NSAID sulindac can be chemically modified to selectively design out its COX-1 and COX-2 inhibitory activity. Unexpectedly, certain derivatives that were synthesized based on in silico modeling displayed increased potency to inhibit tumor cell growth. Other experiments have shown that sulindac can inhibit phosphodiesterase to increase intracellular cyclic GMP levels and that this activity is closely associated with its ability to selectively induce apoptosis of tumor cells. Together, these studies suggest that COX-independent mechanisms can be targeted to develop safer and more efficacious drugs for cancer chemoprevention.

| S-EPMC4034002 | biostudies-literature

miR-27b synergizes with anticancer drugs

Project description:Drug resistance, caused by complex and redundant mechanisms, is a major obstacle in cancer treatment, especially in liver and kidney cancers. Combinational therapy of miRNAs, which concurrently target multiple pathways, with anticancer drugs represent a new strategy to improve the drug response. By a systems approach, we identified that miR-27b, a miRNA deleted in liver and kidney cancers, sensitizes cancer cells to a broad spectrum of anticancer drugs in vitro and in vivo. Two samples transfected with nontarget miRNA control or miR-27b mimics followed by 48 hours doxorubicin treatment

2014-01-07 | E-GEOD-53872 | biostudies-arrayexpress

miR-27b synergizes with anticancer drugs

2014-01-07 | GSE53872 | GEO

Structural basis for Smoothened receptor modulation and chemoresistance to anticancer drugs.

Project description:The Smoothened receptor (SMO) mediates signal transduction in the hedgehog pathway, which is implicated in normal development and carcinogenesis. SMO antagonists can suppress the growth of some tumours; however, mutations at SMO have been found to abolish their antitumour effects, a phenomenon known as chemoresistance. Here we report three crystal structures of human SMO bound to the antagonists SANT1 and Anta XV, and the agonist, SAG1.5, at 2.6-2.8 Å resolution. The long and narrow cavity in the transmembrane domain of SMO harbours multiple ligand binding sites, where SANT1 binds at a deeper site as compared with other ligands. Distinct interactions at D473(6.54f) elucidated the structural basis for the differential effects of chemoresistance mutations on SMO antagonists. The agonist SAG1.5 induces a conformational rearrangement of the binding pocket residues, which could contribute to SMO activation. Collectively, these studies reveal the structural basis for the modulation of SMO by small molecules.

| S-EPMC4198951 | biostudies-literature

On the interaction of an anticancer trisubstituted naphthalene diimide with G-quadruplexes of different topologies: a structural insight.

Project description:Naphthalene diimides showed significant anticancer activity in animal models, with therapeutic potential related to their ability to strongly interact with G-quadruplexes. Recently, a trifunctionalized naphthalene diimide, named NDI-5, was identified as the best analogue of a mini-library of novel naphthalene diimides for its high G-quadruplex binding affinity along with marked, selective anticancer activity, emerging as promising candidate drug for in vivo studies. Here we used NMR, dynamic light scattering, circular dichroism and fluorescence analyses to investigate the interactions of NDI-5 with G-quadruplexes featuring either parallel or hybrid topology. Interplay of different binding modes of NDI-5 to G-quadruplexes was observed for both parallel and hybrid topologies, with end-stacking always operative as the predominant binding event. While NDI-5 primarily targets the 5'-end quartet of the hybrid G-quadruplex model (m-tel24), the binding to a parallel G-quadruplex model (M2) occurs seemingly simultaneously at the 5'- and 3'-end quartets. With parallel G-quadruplex M2, NDI-5 formed stable complexes with 1:3 DNA:ligand binding stoichiometry. Conversely, when interacting with hybrid G-quadruplex m-tel24, NDI-5 showed multiple binding poses on a single G-quadruplex unit and/or formed different complexes comprising two or more G-quadruplex units. NDI-5 produced stabilizing effects on both G-quadruplexes, forming complexes with dissociation constants in the nM range.

| S-EPMC7708068 | biostudies-literature

New insights into therapeutic activity and anticancer properties of curcumin.

Project description:Natural compounds obtained from plants are capable of garnering considerable attention from the scientific community, primarily due to their ability to check and prevent the onset and progress of cancer. These natural compounds are primarily used due to their nontoxic nature and the fewer side effects they cause compared to chemotherapeutic drugs. Furthermore, such natural products perform even better when given as an adjuvant along with traditional chemotherapeutic drugs, thereby enhancing the potential of chemotherapeutics and simultaneously reducing their undesired side effects. Curcumin, a naturally occurring polyphenol compound found in the plant Curcuma longa, is used as an Indian spice. It regulates not only the various pathways of the immune system, cell cycle checkpoints, apoptosis, and antioxidant response but also numerous intracellular targets, including pathways and protein molecules controlling tumor progression. Many recent studies conducted by major research groups around the globe suggest the use of curcumin as a chemopreventive adjuvant molecule to maximize and minimize the desired effects and side effects of chemotherapeutic drugs. However, low bioavailability of a curcumin molecule is the primary challenge encountered in adjuvant therapy. This review explores different therapeutic interactions of curcumin along with its targeted pathways and molecules that are involved in the regulation of onset and progression of different types of cancers, cancer treatment, and the strategies to overcome bioavailability issues and new targets of curcumin in the ever-growing field of cancer.

| S-EPMC5386596 | biostudies-literature

A new tubulin-binding site and pharmacophore for microtubule-destabilizing anticancer drugs.

Project description:The recent success of antibody-drug conjugates (ADCs) in the treatment of cancer has led to a revived interest in microtubule-destabilizing agents. Here, we determined the high-resolution crystal structure of the complex between tubulin and maytansine, which is part of an ADC that is approved by the US Food and Drug Administration (FDA) for the treatment of advanced breast cancer. We found that the drug binds to a site on β-tubulin that is distinct from the vinca domain and that blocks the formation of longitudinal tubulin interactions in microtubules. We also solved crystal structures of tubulin in complex with both a variant of rhizoxin and the phase 1 drug PM060184. Consistent with biochemical and mutagenesis data, we found that the two compounds bound to the same site as maytansine and that the structures revealed a common pharmacophore for the three ligands. Our results delineate a distinct molecular mechanism of action for the inhibition of microtubule assembly by clinically relevant agents. They further provide a structural basis for the rational design of potent microtubule-destabilizing agents, thus opening opportunities for the development of next-generation ADCs for the treatment of cancer.

| S-EPMC4183314 | biostudies-literature

Targeting G-quadruplexes in gene promoters: a novel anticancer strategy?

Project description:G-quadruplexes are four-stranded DNA structures that are over-represented in gene promoter regions and are viewed as emerging therapeutic targets in oncology, as transcriptional repression of oncogenes through stabilization of these structures could be a novel anticancer strategy. Many gene promoter G-quadruplexes have physicochemical properties and structural characteristics that might make them druggable, and their structural diversity suggests that a high degree of selectivity might be possible. Here, we describe the evidence for G-quadruplexes in gene promoters and discuss their potential as therapeutic targets, as well as progress in the development of strategies to harness this potential through intervention with small-molecule ligands.

| S-EPMC3119469 | biostudies-literature

Towards Gram-positive antivirulence drugs: new inhibitors of Streptococcus agalactiae Stk1.

Project description:A structure-activity relationship study from a screening hit and structure-based design strategy has led to the identification of bisarylureas as potent inhibitors of Streptococcus agalactiae Stk1. As this target has been directly linked to bacterial virulence, these inhibitors can be considered as a promising step towards antivirulence drugs.

| S-EPMC2923816 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data