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Histone Methyltransferase

The DOT1L inhibitor Pinometostat decreases the host-response against infections: Considerations about its use in human therapy

17 views | Mar 03 2020

Marcos-Villar Let al. supported a possible increased vulnerability to infection in MLL-r leukemia patients undergoing pinometostat treatment. Close follow up of infection should be considered in pinometostat therapy to reduce some severe side effects during the treatment. [Read the Full Post]

Menin regulates the serine biosynthetic pathway in Ewing sarcoma

0 views | Feb 04 2020

Svoboda LK et al. demonstrated that the SSP is highly active in Ewing sarcoma and that its oncogenic activation is maintained, at least in part, by menin-dependent epigenetic mechanisms involving trithorax complexes. [Read the Full Post]

EZH2 targeting reduces medulloblastoma growth through epigenetic reactivation of the BAI1/p53 tumor suppressor pathway

30 views | Jan 31 2020

Zhang H et al. demonstrated that reactivation of BAI1 expression underlies EPZ-6438 antitumorigenic action, and provided preclinical proof-of-principle evidence for targeting EZH2 in patients with MB. [Read the Full Post]

DZNep is a global histone methylation inhibitor that reactivates developmental genes not silenced by DNA methylation

0 views | Dec 01 2019

Miranda TB et al. found that upon removal of DZNep, gene expression is reduced to its original state. This suggests that there is a homeostatic mechanism that returns the histone modifications to their "ground state" after DZNep treatment. Our data show the strong need for further development of histone methylation inhibitors. [Read the Full Post]

3-Deazaneplanocin A and neplanocin A analogues and their effects on apoptotic cell death

49 views | Dec 01 2019

Tam EK et al. identified three compounds that show similar activities to DzNep. Two of these compounds show good pharmacokinetics and safety profiles. Attempts to correlate the observed synergistic apoptotic activities with measured S-adenosylhomocysteine hydrolase (SAHH) inhibitory activities suggest that the apoptotic activity of DzNep might not be directly due to its inhibition of SAHH. [Read the Full Post]

Tri-methylation of H3K79 is decreased in TGF-β1-induced epithelial-to-mesenchymal transition in lung cancer

165 views | Nov 29 2019

Evanno E et al. showed that histone methylation was modified during EMT, and combination of epigenetic compounds with conventional or targeted chemotherapy might contribute to reduce metastasis and to enhance clinical responses. [Read the Full Post]

Regulation of PRMT5-MDM4 axis is critical in the response to CDK4/6 inhibitors in melanoma

100 views | Oct 16 2019

AbuHammad S et al. provided a strong rationale for further investigation of novel combinations of CDK4/6 and PRMT5 inhibitors, not only in melanoma but other tumor types, including breast, pancreatic, and esophageal carcinoma. [Read the Full Post]

Blocking EZH2 methylation transferase activity by GSK126 decreases stem cell-like myeloma cells

0 views | Aug 27 2019

Zeng D et al. suggested that EZH2 inactivation by GSK126 is effective in killing MM cells and CSCs as a single agent or in combination with bortezomib. Clinical trial of GSK126in patients with MM may be warranted. [Read the Full Post]

Selective inhibition of EZH2 by EPZ-6438 leads to potent antitumor activity in EZH2-mutant non-Hodgkin lymphoma

110 views | Aug 19 2019

Knutson SK et al. indicated these data confirm the dependency of EZH2-mutant NHL on EZH2 activity and portend the utility of EPZ-6438 as a potential treatment for these genetically defined cancers. [Read the Full Post]

A patent review of arginine methyltransferase inhibitors (2010-2018)

130 views | Jul 10 2019

Li X et al. summarized the updated patented inhibitors targeting PRMTs from 2010 to 2018. The authors illustrate the chemical structures, molecular mechanism of action, pharmacological activities as well as the potential clinical application including combination therapy and biomarker-guided therapy. PRMT inhibitors in clinical trials are also highlighted. The authors provide a future perspective for further development of potent and selective PRMT inhibitors. [Read the Full Post]