Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

A Study of TAK-186 (Also Known as MVC-101) in Adults With Advanced or Metastatic Cancer

ABSTRACT: The main aim of this study is to check for side effects and tolerability of TAK-186 (also known as MVC-101) in adults with unremovable advanced or metastatic cancer. Another aim is to characterize and evaluate the activity of TAK-186 (MVC-101). Participants may receive treatment throughout the study for a maximum of 13 months and will be followed up at 30 days and then every 12 weeks for up to 48 weeks after the last treatment.

DISEASE(S): Carcinoma, Squamous Cell,Neoplasm Metastasis,Lung Cancer,Nsclc,Squamous Cell Cancer Of Head And Neck (scchn),Colon Cancer,Colorectal Cancer,Head And Neck Neoplasms,Non-small Cell Lung Cancer (nsclc),Neoplasms, Squamous Cell

PROVIDER: 2374243 | ecrin-mdr-crc |

REPOSITORIES: ECRIN MDR

ACCESS DATA

Json Xml

Similar Datasets

TAK-981

Project description:TAK-981

| PRJNA723842 | ENA

Transcriptome analysis of HeLa cells treated with the CDC7-specific inhibitor TAK-931 [RNA-seq]

Project description:The results showed that 48-h treatment upregulated 138 genes and 72-h treatment upregulated 504 genes. In the Metascape analyses, the TNF signaling pathway was a dominant network module in the 48-h treatment group, while the inflammatory-related modules were more intensively accumulated, and the signaling networks expanded to the surrounding various modules in the 72-h treatment. Our signaling module results indicate that the TAK-931-induced cellular senescence progressed in a time-dependent manner, and mTOR pathways plays important roles in viability for TAK-931-induced senescent cells.

2023-11-05 | GSE245063 | GEO

Marchantia polymorpha subsp. ruderalis cultivar:Tak-1 + Tak-2

Project description:Marchantia polymorpha subsp. ruderalis cultivar:Tak-1 + Tak-2 Genome sequencing and assembly

| PRJNA310693 | ENA

Marchantia polymorpha subsp. ruderalis strain:Tak-1 and Tak-2

Project description:Marchantia polymorpha whole-genome sequencing for strains Tak-1 and Tak-2

| PRJDB16711 | ENA

Targeting Pancreatic Cancer by TAK-981, a SUMOylation Inhibitor that Activates the Immune System and Blocks Tumor Cell Cycle Progression

Project description:The 5-year survival rate of pancreatic ductal adenocarcinoma (PDAC) is lower than 8%. PDAC has the characteristics of high-density stroma and a distinctive immunosuppressive microenvironment and is profoundly resistant to all forms of chemo and immunotherapy. SUMOylation is a reversible post-translational modification required for cell cycle progression. We found that SUMOylation is increased in PDAC patient samples compared to primary pancreatic tissue. TAK-981, a novel highly selective and potent small molecule inhibitor of the SUMO activation enzyme E1 (SAE), selectively decreased SUMOylation in PDAC cells at the nanomolar range, thereby causing a G2/M cell cycle arrest, mitotic failure and chromosomal segregation defects. In vivo TAK-981 efficiently limited the tumor burden in the KPC3 syngeneic mouse model without evidence of general toxicity. Interestingly, we found that TAK-981 modulates the immune system, up-regulating CD8+ T cells, NK cells and down-regulating B cells in peripheral blood, spleen, lymph nodes. Treatment of mouse primary T cells ex vivo with TAK-981 activated STAT1, the key transcription factor induced by interferon signaling. Our findings indicate that inhibition of the SUMO pathway might be a potential clinical strategy to target PDAC by inhibiting tumor cell division and activating anti-tumor immunity.

2022-01-10 | PXD024521 | Pride

A genome-wide CRISPR/Cas9 screen in acute myeloid leukemia cells identifies regulators of TAK-243 sensitivity

Project description:TAK-243 is a first-in-class inhibitor of ubiquitin-like modifier activating enzyme 1 (UBA1) that catalyzes ubiquitin activation, the first step in the ubiquitylation cascade. Based on its preclinical efficacy and tolerability, TAK-243 has been advanced to phase 1 clinical trials in advanced malignancies. Nonetheless, the determinants of TAK-243 sensitivity remain largely unknown. Here, we conducted a genome-wide CRISPR/Cas9 knockout screen in acute myeloid leukemia (AML) cells in the presence of TAK-243 to identify genes essential for TAK-243 action. We identified BEN domain-containing protein 3 (BEND3), a transcriptional repressor and a regulator of chromatin organization, as the top gene whose knockout confers resistance to TAK-243

2021-01-13 | GSE164639 | GEO

Comparative hepatic transcriptome analyses revealed possible pathogenic mechanisms of fasiglifam (TAK-875)-induced acute liver injury in mice

Project description:Fasiglifam (TAK-875), a G protein-coupled receptor 40 (GPR40) agonist, was a drug candidate for type 2 diabetes. However, its development was terminated in phase 3 trials due to liver safety concerns. Although TAK-875 was reported to inhibit hepatobiliary transporters and disturb bile acid disposition, pathogenic mechanisms of TAK-875-induced liver injury are not fully understood. In this study, we sought to identify the mechanisms with a hepatic genome-wide transcriptomic analysis in a murine model. We demonstrated that, among the three GPR40 agonists, TAK-875, AMG-837 and TUG-770, only TAK-875 induced acute liver injury in mice. Transcriptome profiles of TAK-875-exposed liver was compared with those of non-hepatotoxic analogues AMG-837 and TUG-770 as negative controls and those of classical hepatotoxicants concanavalin A and carbon tetrachloride as positive controls. The comparative hepatic transcriptome analyses revealed the enrichment of genes involved in inflammation, endoplasmic reticulum (ER) stress, apoptosis, and hepatic lipid accumulation, suggesting that these events play pathophysiologic roles in the development of TAK-875-induced liver injury. These results were validated by quantitative PCR with significant changes in chemokines, danger signals, ER stress mediators, proapoptotic factors, and hepatic steatosis markers only in TAK-875-exposed liver. Pretreatment of TAK-875-administered mice with an ER stress inhibitor 4-phenylbutyric acid (4-PBA) alleviated the liver injury. Consistent with the in vivo study, pretreatment of HepG2 cells with 4-PBA significantly improved the decrease of cell viability induced by TAK-875. In conclusion, by a comprehensive transcriptomic analysis of GPR40 agonists, we found multiple possible processes that contribute to TAK-875-induced acute liver injury in mice.

2018-10-10 | GSE112140 | GEO

The SUMOylation inhibitor TAK-981 induces a transcriptional reprogramming in human Natural Killer cells [RNA-seq]

Project description:SUMOylation, a post-translational modification of the ubiquitin family plays a critical role in the regulation of proteins function and fate. TAK-981 (Subasumstat) is a first-in-class inhibitor of the SUMO-activating enzyme used in various phase I/II clinical trials for solid tumors and lymphomas. In addition to its direct cytotoxic effect on cancer cells, TAK-981 activates anti-tumor immune response. We show here that TAK-981 activates human natural killer cells. TAK-981 mostly regulates genes involved in inflammation and immune response, in particular those related to the type-I and type-II interferon pathway.

2024-02-28 | GSE255279 | GEO

Gene expression profile at single cell level of HeLa cells treated with the CDC7-specific inhibitor TAK-931 [scRNA-seq]

Project description:We performed scRNA-seq analyses to determine the transcriptional landscape of the TAK-931-induced aneuploid cells at the single-cell levels. HeLa cells were treated with DMSO or TAK-931 (300 nM) for 72 h. In the t-SNE plots, the DMSO- and TAK-931-treated cells were classified in two distinct clusters. Indicating that the major population of the TAK-931-treated aneuploid HeLa cells was transformed to a cell contexture that was transcriptionally distinct from that of DMSO-treated control cells. The hallmark of an inflammatory response was remarkably enriched in the TAK-931 treatment cluster. In addition, the positive cells of inflammatory cytokine/chemokine-related genes, such as CXCL8, IL1B, TNHSF14 and TNFRSF1B, were significantly accumulated in the TAK-931-treatment cluster.

2023-11-05 | GSE244987 | GEO

SUMOylation inhibitor TAK-981 (Subasumstat) synergizes with 5-azacitidine in preclinical models of acute myeloid leukemia

Project description:Acute Myeloid Leukemias (AML) are severe hematomalignancies with dismal prognosis. The post-translational modification SUMOylation plays key roles in leukemogenesis and AML response to therapies. Here, we show that TAK-981 (subasumstat), a first-in-class SUMOylation inhibitor, is endowed with potent anti-leukemic activity in various preclinical models of AML. TAK-981 targets AML cell lines and patient blast cells in vitro and in vivo in xenografted mice with minimal toxicity on normal hematopoietic cells. Moreover, it synergizes with 5-azacitidine (AZA), a DNA-hypomethylating agent now used in combination with the BCL-2 inhibitor venetoclax to treat AML patients unfit for standard chemotherapies. Interestingly, TAK-981+AZA combination shows higher anti-leukemic activity than AZA+venetoclax combination both in vitro and in vivo, at least in the models tested. Mechanistically, TAK-981 potentiates the transcriptional reprogramming induced by AZA, promoting apoptosis, alteration of the cell cycle and differentiation of the leukemic cells. In addition, TAK-981+AZA treatment induces many genes linked to inflammation and immune response pathways. In particular, this leads to the secretion of type I interferon (IFN-I) by AML cells. Finally, TAK-981+AZA induces the expression of Natural Killer (NK)-activating ligands (MICA/B) and adhesion proteins (ICAM-1) at the surface of AML cells. Consistently, TAK-981+AZA-treated AML cells activate NKs and increase their cytotoxic activity. Targeting SUMOylation with TAK-981 may thus be a promising strategy to both sensitize AML cells to AZA and reduce their immune-escape capacities.

2023-08-29 | GSE212330 | GEO

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