Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Online informatics resources to facilitate cancer target and chemical probe discovery

ABSTRACT: This review highlights the cutting-edge informatics resources available to explore cancer genomics, biological, and chemical space to facilitate target and therapeutic discovery in cancer. The advances in cancer genomics, chemical biology, high-throughput screening technologies, and synthetic medicinal chemistry have tremendously expanded the biological space of cancer targets and chemical space of bioactive small molecules to interrogate oncogenic signaling. To explore and leverage these exponentially growing cancer-associated data, a great number of computational tools, databases, and algorithms have been developed. This review summarizes recent cancer-related web resources that allow researchers working at the interface of chemical, biological, and cancer genomics fields to integrate clinical and genomics data for specific actionable targets and selective chemical compounds to facilitate cancer therapeutic discovery.

SUBMITTER: Yang X

PROVIDER: S-EPMC7429978 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Web resources facilitate drug discovery in treatment of COVID-19.

Project description:The infectious disease Coronavirus 2019 (COVID-19) continues to cause a global pandemic and, thus, the need for effective therapeutics remains urgent. Global research targeting COVID-19 treatments has produced numerous therapy-related data and established data repositories. However, these data are disseminated throughout the literature and web resources, which could lead to a reduction in the levels of their use. In this review, we introduce resource repositories for the development of COVID-19 therapeutics, from the genome and proteome to antiviral drugs, vaccines, and monoclonal antibodies. We briefly describe the data and usage, and how they advance research for therapies. Finally, we discuss the opportunities and challenges to preventing the pandemic from developing further.

| S-EPMC8056987 | biostudies-literature

Discovery of a PCAF Bromodomain Chemical Probe.

Project description:The p300/CBP-associated factor (PCAF) and related GCN5 bromodomain-containing lysine acetyl transferases are members of subfamily?I of the bromodomain phylogenetic tree. Iterative cycles of rational inhibitor design and biophysical characterization led to the discovery of the triazolopthalazine-based L-45 (dubbed L-Moses) as the first potent, selective, and cell-active PCAF bromodomain (Brd) inhibitor. Synthesis from readily available (1R,2S)-(-)-norephedrine furnished L-45 in enantiopure form. L-45 was shown to disrupt PCAF-Brd histone H3.3 interaction in cells using a nanoBRET assay, and a co-crystal structure of L-45 with the homologous Brd PfGCN5 from Plasmodium falciparum rationalizes the high selectivity for PCAF and GCN5 bromodomains. Compound L-45 shows no observable cytotoxicity in peripheral blood mononuclear cells (PBMC), good cell-permeability, and metabolic stability in human and mouse liver microsomes, supporting its potential for in?vivo use.

| S-EPMC5412877 | biostudies-literature

Discovery of a chemical probe for PRDM9.

Project description:PRDM9 is a PR domain containing protein which trimethylates histone 3 on lysine 4 and 36. Its normal expression is restricted to germ cells and attenuation of its activity results in altered meiotic gene transcription, impairment of double-stranded breaks and pairing between homologous chromosomes. There is growing evidence for a role of aberrant expression of PRDM9 in oncogenesis and genome instability. Here we report the discovery of MRK-740, a potent (IC50: 80?±?16?nM), selective and cell-active PRDM9 inhibitor (Chemical Probe). MRK-740 binds in the substrate-binding pocket, with unusually extensive interactions with the cofactor S-adenosylmethionine (SAM), conferring SAM-dependent substrate-competitive inhibition. In cells, MRK-740 specifically and directly inhibits H3K4 methylation at endogenous PRDM9 target loci, whereas the closely related inactive control compound, MRK-740-NC, does not. The discovery of MRK-740 as a chemical probe for the PRDM subfamily of methyltransferases highlights the potential for exploiting SAM in targeting SAM-dependent methyltransferases.

| S-EPMC6917776 | biostudies-literature

Chemical informatics and target identification in a zebrafish phenotypic screen.

Project description:Target identification is a core challenge in chemical genetics. Here we use chemical similarity to computationally predict the targets of 586 compounds that were active in a zebrafish behavioral assay. Among 20 predictions tested, 11 compounds had activities ranging from 1 nM to 10,000 nM on the predicted targets. The roles of two of these targets were tested in the original zebrafish phenotype. Prediction of targets from chemotype is rapid and may be generally applicable.

| S-EPMC3262069 | biostudies-literature

Function-first proteomic strategies for chemical probe discovery in human cells

Project description:Transcriptional consequences of Pladienolide B, WX-02-23, and WX-02-43 treatment in 22Rv1 cells by RNA-sequencing

2023-04-19 | GSE185373 | GEO

Discovery of an MLLT1/3 YEATS Domain Chemical Probe.

Project description:YEATS domain (YD) containing proteins are an emerging class of epigenetic targets in drug discovery. Dysregulation of these modified lysine-binding proteins has been linked to the onset and progression of cancers. We herein report the discovery and characterisation of the first small-molecule chemical probe, SGC-iMLLT, for the YD of MLLT1 (ENL/YEATS1) and MLLT3 (AF9/YEATS3). SGC-iMLLT is a potent and selective inhibitor of MLLT1/3-histone interactions. Excellent selectivity over other human YD proteins (YEATS2/4) and bromodomains was observed. Furthermore, our probe displays cellular target engagement of MLLT1 and MLLT3. The first small-molecule X-ray co-crystal structures with the MLLT1 YD are also reported. This first-in-class probe molecule can be used to understand MLLT1/3-associated biology and the therapeutic potential of small-molecule YD inhibitors.

| S-EPMC6348381 | biostudies-literature

The dental informatics online community.

Project description:Dental Informatics (DI) is the application of computer and information science to improve dental practice, research, education, and program administration. To support the growth of this emerging discipline, we created the Dental Informatics Online Community (DIOC). The DIOC provides a dedicated professional home for DI researchers and serves as an open, common, and worldwide forum for all individuals interested in the field. It was created and is maintained by the Center for Dental Informatics at the University of Pittsburgh School of Dental Medicine, independent from any professional association, corporate interest or funding source. The DIOC's Website provides many useful features, such as a learning center, publication archive, member and project directories, and the Current Awareness Service (CAS). The CAS automatically notifies members about new information added to the Community. Notifications are individualized according to a member's profile and activities on the site. The DIOC is a research-oriented online community which provides resources in the dental informatics and dental technology field, as well as a way to establish social connections to share ideas, problems and research opportunities. Member and activity growth since the community's inception in 2005 have been steady, but future sustainability of the community depends on many factors.

| S-EPMC3043354 | biostudies-literature

AD Informer Set: Chemical tools to facilitate Alzheimer's disease drug discovery.

Project description:IntroductionThe portfolio of novel targets to treat Alzheimer's disease (AD) has been enriched by the Accelerating Medicines Partnership Program for Alzheimer's Disease (AMP AD) program.MethodsPublicly available resources, such as literature and databases, enabled a data-driven effort to identify existing small molecule modulators for many protein products expressed by the genes nominated by AMP AD and suitable positive control compounds to be included in the set. Compounds contained within the set were manually selected and annotated with associated published, predicted, and/or experimental data.ResultsWe built an annotated set of 171 small molecule modulators targeting 98 unique proteins that have been nominated by AMP AD consortium members as novel targets for the treatment of AD. The majority of compounds included in the set are inhibitors. These small molecules vary in their quality and should be considered chemical tools that can be used in efforts to validate therapeutic hypotheses, but which will require further optimization. A physical copy of the AD Informer Set can be requested on the Target Enablement to Accelerate Therapy Development for Alzheimer's Disease (TREAT-AD) website.DiscussionSmall molecules that enable target validation are important tools for the translation of novel hypotheses into viable therapeutic strategies for AD.

| S-EPMC9019904 | biostudies-literature

Discovery of a chemical probe for the L3MBTL3 methyllysine reader domain.

Project description:We describe the discovery of UNC1215, a potent and selective chemical probe for the methyllysine (Kme) reading function of L3MBTL3, a member of the malignant brain tumor (MBT) family of chromatin-interacting transcriptional repressors. UNC1215 binds L3MBTL3 with a K(d) of 120 nM, competitively displacing mono- or dimethyllysine-containing peptides, and is greater than 50-fold more potent toward L3MBTL3 than other members of the MBT family while also demonstrating selectivity against more than 200 other reader domains examined. X-ray crystallography identified a unique 2:2 polyvalent mode of interaction between UNC1215 and L3MBTL3. In cells, UNC1215 is nontoxic and directly binds L3MBTL3 via the Kme-binding pocket of the MBT domains. UNC1215 increases the cellular mobility of GFP-L3MBTL3 fusion proteins, and point mutants that disrupt the Kme-binding function of GFP-L3MBTL3 phenocopy the effects of UNC1215 on localization. Finally, UNC1215 was used to reveal a new Kme-dependent interaction of L3MBTL3 with BCLAF1, a protein implicated in DNA damage repair and apoptosis.

| S-EPMC3577944 | biostudies-literature

Compound prioritization methods increase rates of chemical probe discovery in model organisms.

Project description:Preselection of compounds that are more likely to induce a phenotype can increase the efficiency and reduce the costs for model organism screening. To identify such molecules, we screened ~81,000 compounds in Saccharomyces cerevisiae and identified ~7500 that inhibit cell growth. Screening these growth-inhibitory molecules across a diverse panel of model organisms resulted in an increased phenotypic hit-rate. These data were used to build a model to predict compounds that inhibit yeast growth. Empirical and in silico application of the model enriched the discovery of bioactive compounds in diverse model organisms. To demonstrate the potential of these molecules as lead chemical probes, we used chemogenomic profiling in yeast and identified specific inhibitors of lanosterol synthase and of stearoyl-CoA 9-desaturase. As community resources, the ~7500 growth-inhibitory molecules have been made commercially available and the computational model and filter used are provided.

| S-EPMC4193902 | 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