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Methylation

Sotorasib Tackles KRASG12C-Mutated Pancreatic Cancer

46 | Apr 19 2022

Xinting Zheng et al. found that the mechanisms of resistance to sotorasib and determine the efficacy and safety of combination therapy for the treatment of NSCLC containing the KRAS G12C mutation. [Read the Full Post]

[Magnetic resonance imaging analysis on the effect of marathon on the dynamic changes of morphological characteristics of patellar tendon in amateur marathon runners after half marathon]

41 | Apr 06 2022

Y Zhang et al. thought that marathon had effect on the normal PT morphology in male amateur marathon runners, showing an increase in proximal CSA. [Read the Full Post]

JIB-04 Has Broad-Spectrum Antiviral Activity and Inhibits SARS-CoV-2 Replication and Coronavirus Pathogenesis

93 | Apr 03 2022

Juhee Son et al. found that a limited but still promising utility of JIB-04 as an antiviral agent in the combat against COVID-19 and potentially other viral diseases. [Read the Full Post]

A comprehensive study of epigenetic alterations in hepatocellular carcinoma identifies potential therapeutic targets

0 | Mar 23 2022

Juan Bayo et al. thought that the epigenetic alterations identified in HCC could be used to predict prognosis and to define a subgroup of high-risk patients that would potentially benefit from JmjC inhibitor therapy. [Read the Full Post]

AZD5153 reverses palbociclib resistance in ovarian cancer by inhibiting cell cycle-related proteins and the MAPK/PI3K-AKT pathway

88 | Mar 22 2022

Chen Liu et al. revealed that it was anticipated that this class of drugs, including AZD5153, which inhibited the cell cycle-related protein and MAPK/PI3K-AKT pathway, would exhibit synergistic effects with palbociclib in OC. [Read the Full Post]

Recruitment of MLL1 complex is essential for SETBP1 to induce myeloid transformation

100 | Mar 11 2022

Nhu Nguyen et al. thought that the MLL1 complex played a critical role in Setbp1-induced transcriptional activation and transformation. [Read the Full Post]

Discovery and Pharmacological Characterization of JNJ-64619178, a Novel Small-Molecule Inhibitor of PRMT5 with Potent Antitumor Activity

62 | Mar 08 2022

Dirk Brehmer et al. supported the continued clinical evaluation of JNJ-64619178 in patients with aberrant PRMT5 activity-driven tumors. [Read the Full Post]

EPZ015666, a selective protein arginine methyltransferase 5 (PRMT5) inhibitor with an antitumour effect in retinoblastoma

0 | Jan 23 2022

Xing Liu et al. found that PRMT5 promoted retinoblastoma growth, the PRMT5 inhibitor EPZ015666 inhibited retinoblastoma in vitro by regulating P53-P21/P27-CDK2 signaling pathways and slowed retinoblastoma growth in a xenograft model. [Read the Full Post]

Protein Arginine Methyltransferase 5 Promotes the Migration of AML Cells by Regulating the Expression of Leukocyte Immunoglobulin-Like Receptor B4

101 | Jan 22 2022

Lu Zhao found that PRMT5 plays an important role in the invasion of AML, which acts via regulating the expression of LILRB4. PRMT5 could act as a potential therapeutic candidate for AML. Copyright © 2021 Lu Zhao et al. [Read the Full Post]

Disruptor of telomeric silencing 1-like promotes ovarian cancer tumor growth by stimulating pro-tumorigenic metabolic pathways and blocking apoptosis

0 | Jan 07 2022

Suresh Chava et al. found that DOT1L promoted ovarian cancer tumor growth by regulating apoptotic and metabolic pathways as well as NK cell-mediated eradication of ovarian cancer. [Read the Full Post]

Comprehensive in Vitro Characterization of the LSD1 Small Molecule Inhibitor Class in Oncology

162 | Jan 05 2022

Natalia Sacilotto et al. highlighted significant differences in potency and selectivity among the clinical compounds with iadademstat being the most potent and revealed that most of the tool compounds had very low activity and selectivity. [Read the Full Post]

HO-1 promotes resistance to an EZH2 inhibitor through the pRB-E2F pathway: correlation with the progression of myelodysplastic syndrome into acute myeloid leukemia

128 | Dec 26 2021

Zhengchang He et al. found that HO-1 could influence MDS resistance and progression to AML. [Read the Full Post]

Biological Effects of BET Inhibition by OTX015 (MK-8628) and JQ1 in NPM1-Mutated (NPM1c) Acute Myeloid Leukemia (AML)

202 | Dec 13 2021

Hanane Djamai et al. found that BETi, similar to ATO + ATRA, induced differentiation and apoptosis which was TP53 independent in the NPM1c cell line OCI-AML3 and primary cells. [Read the Full Post]

Non-canonical H3K79me2-dependent pathways promote the survival of MLL-rearranged leukemia

242 | Nov 27 2021

William F Richter et al. found that this pathway also depends on MLL1, indicating combinations of DOT1L, MLL1 and FLT3 inhibitors should be explored for treating FLT3-mutant leukemia. [Read the Full Post]

Menin‑MLL inhibitors induce ferroptosis and enhance the anti‑proliferative activity of auranofin in several types of cancer cells

535 | Nov 05 2021

Ichiroh Kato et al. thought that menin‑MLL inhibitors, such as MI‑463, in combination with auranofin represented an effective therapeutic approach for several types of cancer via the induction of ferroptosis. [Read the Full Post]

Disruptor of telomeric silencing 1-like promotes ovarian cancer tumor growth by stimulating pro-tumorigenic metabolic pathways and blocking apoptosis

357 | Sep 28 2021

Suresh Chava et al. demonstrated that DOT1L promoted ovarian cancer tumor growth by regulating apoptotic and metabolic pathways as well as NK cell-mediated eradication of ovarian cancer and identified DOT1L as a new pharmacological target for ovarian cancer therapy. [Read the Full Post]

Overexpression of UTX promotes tumor progression in Oral tongue squamous cell carcinoma patients receiving surgical resection: a case control study

289 | Sep 14 2021

Yen-Hao Chen et al. found that UTX played an important role in the process of OTSCC and overexpression of UTX might predict poor prognosis in OTSCC patients who received surgical resection. [Read the Full Post]

Myelocytomatosis-Protein Arginine N-Methyltransferase 5 Axis Defines the Tumorigenesis and Immune Response in Hepatocellular Carcinoma

329 | Aug 24 2021

Yuhong Luo et al. revealed that PRMT5 was an epigenetic executer of MYC, leading to repression of the transcriptional regulation of downstream genes that promoted hepatocellular carcinogenesis. [Read the Full Post]

TCF3 is epigenetically silenced by EZH2 and DNMT3B and functions as a tumor suppressor in endometrial cancer

363 | Jul 28 2021

Tao Gui et al. found that TCF3 functions as a tumor suppressor epigenetically silenced by EZH2 and DNMT3B in EC. [Read the Full Post]

CDKN2A Determines Mesothelioma Cell Fate to EZH2 Inhibition

360 | Jul 22 2021

Giulia Pinton et al. found that the expression of CDKN2A predicted cell fate in response to EZH2 inhibition and could potentially stratify tumors likely to undergo apoptosis. [Read the Full Post]

The bromodomain inhibitor JQ1+ reduces calcium-sensing receptor activity in pituitary cell-lines

490 | Jul 06 2021

Kate E Lines et al. thought that reducing CaSR expression might be a viable option in the treatment of pituitary tumours. [Read the Full Post]

SMALL MOLECULE IMAGING AGENT FOR MUTANT KRAS G12C

342 | May 19 2021

Peter D Koch et al. found that two fluorescent derivatives (BODIPY FL and BODIPY TMR) of ARS-1323 bind mutant KRAS and could be used for biochemical binding screens. [Read the Full Post]

MLL1 combined with GSK3 and MAP2K inhibition improves the development of in vitro-fertilized embryos

389 | Apr 27 2021

Xuejie Han et al. found that the application of 3i provided a new method for improving IVF embryo production in domestic animals. [Read the Full Post]

H3K36 methylation reprograms gene expression to drive early gametocyte development in Plasmodium falciparum

425 | Apr 25 2021

Jessica Connacher et al. found that H3K36me2&3-associated repression of genes was therefore involved in key transcriptional shifts that accompanied the transition from early gametocyte differentiation to intermediate development. [Read the Full Post]

A comprehensive study of epigenetic alterations in hepatocellular carcinoma identifies potential therapeutic targets

552 | Apr 11 2021

Juan Bayo et al. found that mutations and changes in expression of epigenetic modifiers were common events in human hepatocellular carcinoma, leading to an aggressive gene expression program and poor clinical prognosis. [Read the Full Post]

Dissecting the Role of BET Bromodomain Proteins BRD2 and BRD4 in Human NK Cell Function

357 | Apr 10 2021

Adam P Cribbs et al. found that compelling argument for further clinical investigation. [Read the Full Post]

Oxidative stress abrogates the degradation of KMT2D to promote degeneration in nucleus pulposus

342 | Mar 23 2021

Wenbin Xu et al. approved that oxidative stress induced ROS production promote the process of NP degeneration by enhancing KMT2D mediated transcriptional regulation of matrix degeneration related genes during NP degeneration. [Read the Full Post]

Rational Design, synthesis and biological evaluation of novel triazole derivatives as potent and selective PRMT5 inhibitors with antitumor activity

294 | Mar 21 2021

Kongkai Zhu et al. described the design, synthesis and biological evaluation of a series of novel, potent and selective PRMT5 inhibitors with antiproliferative activity against Z-138 mantle cell lymphoma cell line. [Read the Full Post]

EPZ015666, a selective protein arginine methyltransferase 5 (PRMT5) inhibitor with an antitumour effect in retinoblastoma

374 | Jan 29 2021

Xing Liu et al. found that EPZ015666 inhibited retinoblastoma cell proliferation and led to cell cycle arrest at the G1 phase. [Read the Full Post]

Inhibition of PRMT5 Attenuates Oxidative Stress-Induced Pyroptosis via Activation of the Nrf2/HO-1 Signal Pathway in a Mouse Model of Renal Ischemia-Reperfusion Injury

332 | Jan 29 2021

Changhui Diao et al. thought that PRMT5 might be a promising therapeutic target. [Read the Full Post]

Histone methyltransferase DOT1L coordinates AR and MYC stability in prostate cancer

402 | Jan 17 2021

R Vatapalli et al. thought that DOT1L selectively regulated the tumorigenicity of AR-positive prostate cancer cells and was a promising therapeutic target for PCa. [Read the Full Post]

Targeting LSD1 for acute myeloid leukemia (AML) treatment

377 | Jan 14 2021

Shujing Zhang et al. discussed the main epigenetic drugs targeting LSD1 for AML therapy. [Read the Full Post]

Inhibition of Methyltransferase DOT1L Sensitizes to Sorafenib Treatment AML Cells Irrespective of MLL-Rearrangements: A Novel Therapeutic Strategy for Pediatric AML

301 | Dec 09 2020

Annalisa Lonetti et al. highlighted a novel therapeutic strategy for pediatric AML patients. [Read the Full Post]

Menin regulates the serine biosynthetic pathway in Ewing sarcoma

0 | Nov 14 2020

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

Nullifying epigenetic writer DOT1L attenuates neointimal hyperplasia

356 | Sep 22 2020

Yitao Huang et al. presented a strong rationale for continued mechanistic and translational investigation into DOT1L targeting for treatment of (re)stenotic vascular conditions. [Read the Full Post]

Palmitate-TLR4 signaling regulates the histone demethylase, JMJD3, in macrophages and impairs diabetic wound healing

401 | Aug 31 2020

Frank M Davis et al. concluded that palmitate contributed to the chronic Jmjd3-mediated activation of macrophages in diabetic peripheral tissue and a histone demethylase inhibitor-based therapy might represent a novel treatment for nonhealing diabetic wounds. [Read the Full Post]

EZH2 Supports Osteoclast Differentiation and Bone Resorption Via Epigenetic and Cytoplasmic Targets

384 | Aug 08 2020

Juraj Adamik et al. found that EZH2 exhibits complex roles in supporting osteoclast differentiation and function. [Read the Full Post]

PRMT5 control of cGAS/STING and NLRC5 pathways defines melanoma response to antitumor immunity

429 | Aug 03 2020

Hyungsoo Kim et al. provided a rationale to test PRMT5 inhibitors in immunotherapy-based clinical trials as a means to enhance an antitumor immune response. [Read the Full Post]

HMTase Inhibitors as a Potential Epigenetic-Based Therapeutic Approach for Friedreich's Ataxia

422 | Jun 28 2020

Mursal Sherzai et al. showed that a combination treatment of BIX0194 and GSK126, significantly increased FXN gene expression levels and reduced the repressive histone marks. However, no increase in frataxin protein levels was observed. [Read the Full Post]

EZH2 Is Involved in Vulnerability to Neuroinflammation and Depression-Like Behaviors Induced by Chronic Stress in Different Aged Mice

360 | Jun 23 2020

Wei Wang et al. found that EZH2 might be involved in susceptibility to neuroinflammation and depression-like behaviors in different aged mice. [Read the Full Post]

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

498 | 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 | 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

473 | 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]

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

1198 | 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]

Epigenetic Profiling Identifies LIF as a Super-enhancer-Controlled Regulator of Stem Cell-like Properties in Osteosarcoma

572 | Nov 12 2019

Lu B et al. revealed osteosarcoma SE profiles and uncovers a distinct tumor-stemness epigenetic regulatory mechanism in which an osteosarcoma-specific SE-mediated factor, LIF, promotes osteosarcoma stemness gene activation via NOTCH1 signaling pathway. [Read the Full Post]

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

545 | 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 | 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

551 | 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)

602 | 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]

Inhibition of G9a by a small molecule inhibitor, UNC0642, induces apoptosis of human bladder cancer cells

582 | Jun 26 2019

Cao YP et al. demonstrated that G9a may be a promising therapeutic target for UBC, and an epigenetics-based therapy by UNC0642 is suggested. [Read the Full Post]

Elevating H3K27me3 level sensitizes colorectal cancer to oxaliplatin

592 | Jun 06 2019

Wang Q et al. suggested that elevating H3K27me3 level can improve drug sensitivity in CRC patients. [Read the Full Post]

Menin regulates the serine biosynthetic pathway in Ewing sarcoma

718 | May 09 2019

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]

Randomized phase 2 study of low-dose decitabine vs low-dose azacitidine in lower-risk MDS and MDS/MPN

849 | Mar 10 2019

Jabbour E et al. indicated that treatment was well tolerated, with a 6-week mortality rate of 0%. The use of low-dose HMAs is safe and effective in patients with lower-risk MDS and MDS/MPN. Their effect on the natural history of lower-risk disease needs to be further studied. [Read the Full Post]

Inhibition of H3K27me3 Histone Demethylase Activity Prevents the Proliferative Regeneration of Zebrafish Lateral Line Neuromasts

779 | Mar 06 2019

Bao B et al. indicated that H3K27me3 demethylation is a key epigenetic regulator in the process of hair cell regeneration in zebrafish and suggest that H3K27me3 histone demethylase activity might be a novel therapeutic target for the treatment of hearing loss. [Read the Full Post]

Inactivation of PBX3 and HOXA9 by down-regulating H3K79 methylation represses NPM1-mutated leukemic cell survival

746 | Feb 27 2019

Zhang W et al. indicated that NPMc+ leukemic cell survival requires upregulation of PBX3 and HOXA9, and this action can be largely attenuated by a DOT1L inhibitor. [Read the Full Post]

Preclinical evaluation of the BET bromodomain inhibitor BAY 1238097 for the treatment of lymphoma

660 | Jan 02 2019

Bernasconi E et al. indicated the use of combination schemes targeting EZH2, mTOR and BTK alongside BET bromodomains. [Read the Full Post]

BAP1 dependent expression of long non-coding RNA NEAT-1 contributes to sensitivity to gemcitabine in cholangiocarcinoma

661 | Jan 02 2019

Parasramka M et al. showed that NEAT-1 is a downstream effector of gemcitabine sensitivity in CCA. The expression of BAP1 is a determinant of sensitivity to therapeutic drugs that can be exploited to enhance responses through combination strategies. [Read the Full Post]

Menin regulates Inhbb expression through an Akt/Ezh2-mediated H3K27 histone modification

636 | Dec 31 2018

Gherardi S et al. suggested therefore that Menin could take an important part to the Ezh2-epigenetic repressive landscape in many cells and tissues through its capacity to modulate Akt phosphorylation. [Read the Full Post]

Epigenetic drug combination induces remission in mouse xenograft models of pediatric acute myeloid leukemia

896 | Nov 18 2018

Gopalakrishnapillai A et al. indicated the expression of mutant p53 in MV4;11 cells reduced sensitivity to azacitidine-panobinostat combination, suggesting that p53 may be a predictor of response to epigenetic therapy in pediatric AML. [Read the Full Post]

Epigenetic repression of miR-375 is the dominant mechanism for constitutive activation of the PDPK1/RPS6KA3 signalling axis in multiple myeloma.

871 | Oct 12 2018

Tatekawa S et al. showed the universal involvement of overlapping epigenetic dysregulation for abnormal miR-375 repression in MM, which is likely to contribute to myelomagenesis and to subsequent myeloma progression by activating oncogenic signalling pathways. [Read the Full Post]

Multi-omics maps of cotton fibre reveal epigenetic basis for staged single-cell differentiation

1065 | May 06 2018

Wang M et al. illustrated two divergent pathways mediating a continuous increase of DNA methylation and also sheds further light on the epigenetic basis for single-cell differentiation in plants. [Read the Full Post]