DcpS inhib News - LARVOL Sigma

|||||||||| PF-06687859 / Pfizer
Involvements of decapping scavenger enzyme DcpS in the progression of glioblastoma (WCC Halls A-C) - Nov 3, 2023 - Abstract #Neuroscience2023NEUROSCIENCE_7200;
Thus, we focused on RG3039, an decapping scavenger enzyme (DcpS) inhibitor, which can penetrate the blood-brain barrier and be used orally...N-cadherin is one of the major intercellular adhesion molecules and is known to induce interactions such as proliferation and differentiation in various cancer cells. Taken together, these results suggested that DcpS contributes to GBM progression through the expression of N-cadherin, and DcpS selective inhibitors are expected to be a novel treatment for GBM.

|||||||||| PF-06687859 / Pfizer
Journal: Ferroptosis induced by DCPS depletion diminishes hepatic metastasis in uveal melanoma. (Pubmed Central) - Jun 19, 2023
We found that inhibition of DCPS by shRNA or RG3039 induced gene transcript alteration and ferroptosis through reducing the mRNA turnover of GLRX...Furthermore, targeting DCPS diminished hepatic metastasis of UM cells. These findings may shed light on the understanding of DCPS-mediated pre-mRNA metabolic pathway in UM by which disseminated cells gain enhanced malignant features to promote hepatic metastasis, providing a rational target for metastatic colonization in UM.

|||||||||| PF-06687859 / Pfizer
Journal: Targeted Degradation of mRNA Decapping Enzyme DcpS by a VHL-Recruiting PROTAC. (Pubmed Central) - Jul 20, 2022
JCS-1 non-covalently binds DcpS with a RG3039-based warhead and recruits the E3 ligase VHL, which induces potent, rapid, and sustained DcpS degradation in several AML cell lines. JCS-1 serves as a chemical biology tool to interrogate DcpS degradation and associated changes in RNA processes in different cellular contexts, which may be an attractive strategy for the treatment of AML and other DcpS-dependent genetic disorders.

|||||||||| Journal: Effect of the His-Tag Location on Decapping Scavenger Enzymes and Their Hydrolytic Activity toward Cap Analogs. (Pubmed Central) - May 27, 2020
In contrast, both His-tagged C. elegans DcpSs exhibited higher activity toward mGpppG than the native enzyme. mGDP is resistant to enzymatic cleavage by all three forms of human and nematode DcpS.

|||||||||| Journal: The natural antisense transcript NATTD regulates the transcription of decapping scavenger (DcpS) enzyme. (Pubmed Central) - Jan 10, 2020
Chromatin immunoprecipitation assays revealed that knocking-down NATTD transcript with shRNA enhanced the H3K27-Me3 modification at the DcpS promoter. In summary, our studies identified NATTD as a regulator of DcpS transcription through epigenetic mechanisms.

|||||||||| Journal: Decapping Scavenger Enzyme Activity toward N2-Substituted 5' End mRNA Cap Analogues. (Pubmed Central) - Oct 29, 2019
Various alkyl substituents were tested, and cap analogues with a longer than three-carbon chain were nonhydrolyzable by hDcpS and CeDcpS. Resistance of the modified cap analogues to hDcpS and CeDcpS may be associated with their weaker binding with enzymes.

|||||||||| PF-06687859 / Pfizer
Journal: Exploration of novel therapeutic targets in acute myeloid leukemia via genome-wide CRISPR screening (Pubmed Central) - Aug 21, 2019
Importantly, RG3039 exhibited anti-leukemia effects in PDX models. These findings identify DCPS as a novel therapeutic target for AML, shedding new light on the nuclear RNA metabolic pathway in leukemogenesis.



	Diseases Companies Products Productz Mechanisms of Action Sites