Category: 624-49-7

Maeta, Takahiro published the artcileDimethyl fumarate induces apoptosis via inhibiting NF-κB and STAT3 signaling in adult T-cell leukemia/lymphoma cells, Product Details of C6H8O4, the publication is Anticancer Research (2022), 42(5), 2301-2309, database is CAplus and MEDLINE.

Adult T-cell leukemia (ATL) is a peripheral T lymphocytic malignancy caused by human T-cell leukemia virus type 1 (HTLV-1) infection. Despite treatment that includes novel agents that have been developed, most of ATL patients relapse and acquire multidrug resistance. As a result, the creation of newer agents is critical Di-Me fumarate (DMF) has several effects in cancer cells, including cell signaling, proliferation and cell death. However, its antitumor effects on ATL cells remain unknown. In this study, we looked at DMF′s antitumor effects on ATL cells.Materials and methods: We examined the effects of DMF on proliferation and apoptosis using the trypan blue exclusion assay and annexin V/propidium iodide staining in HTLV-1-infected and transformed T-cell lines, MT-1 and MT-2 cells. We also evaluated the effects of DMF on the nuclear factor-kappa B (NF-κB) and signal transducers and activators of transcription 3 (STAT3) signaling pathways and anti-apoptotic proteins by immunoblotting.Results: DMF inhibited proliferation and induced apoptosis in MT-1 and MT-2 cells by activating poly ADP-ribose polymerase (PARP). Furthermore, DMF inhibited the constitutive activation of both canonical and non-canonical NF-κB pathways in MT-2 cells and the non-canonical NF-κB pathway in MT-1 cells. DMF also inhibited the constitutive tyrosine phosphorylation of STAT3 and the expression of anti-apoptotic proteins, c-IAP2 and survivin in both cells.Conclusion: These results indicate that DMF inhibits proliferation and induces apoptosis in HTLV-1-infected and transformed T-cells by suppressing NF-κB and STAT3 signaling pathways. DMF should be investigated further as a novel agent for ATL.

Anticancer Research published new progress about 624-49-7. 624-49-7 belongs to esters-buliding-blocks, auxiliary class Inhibitor,Natural product, name is Dimethyl fumarate, and the molecular formula is C6H8O4, Product Details of C6H8O4.

Referemce:
https://en.wikipedia.org/wiki/Ester,
Ester – an overview | ScienceDirect Topics

Mashima, Kiyomi published the artcileDimethyl fumarate ameliorates graft-versus-host disease by inhibiting T-cell metabolism and immune responses through a reactive oxygen species-dependent mechanism, Quality Control of 624-49-7, the publication is British Journal of Haematology (2022), 197(6), e78-e82, database is CAplus and MEDLINE.

Acute graft-vs.-host disease (GVHD) is among the leading causes of non-relapse mortality and morbidity after allogeneic haematopoietic stem cell transplantation. Di-Me fumarate (DMF), a fumaric acid derivative, is a novel therapeutic agent for relapsing multiple sclerosis and psoriasis. For instance, DMF succinates a key glycolytic enzyme, glyceraldehyde 3-phosphate dehydrogenase (GAPDH), and irreversibly inactivates its enzymic activity, thereby downregulating aerobic glycolysis in CD4+ T cells. This study investigated whether, and if so, how DMF impairs the metabolism and immune responses of antigen-activated Tcells both in vitro and in vivo using a xenogeneic GVHD mouse model. While the number of CD4+ T cells decreased, the proportion of CD25+ FoxP3+ regulatory T cells (Treg) was higher in DMF-treated mice, and thus the total number of Tregs was equivalent in both groups. Given that DMF depletes intracellular GSH levels by forming succinated glutathione, causing dysregulated ROS accumulation in diverse immune cells and cancer cells, we investigated the redox status of T-cell receptor (TCR)- stimulated T cells after DMF treatment and evaluated the association between their metabolic profiles and effector T-cell function. Furthermore, NAC almost completely restored viability (Figure 2F), proliferation (Figure 2G), and interferon gamma (IFN-γ) production (Figure 2H) of TCR-stimulated T cells following DMF treatment. Clin. relevant GVHD model, which show better disease control and prolonged survival by DMF treatment, can be readily translated to clin. settings. Our findings will provide a mol. basis for potential future clin. applications of DMF for the prevention and treatment of GVHD.

British Journal of Haematology published new progress about 624-49-7. 624-49-7 belongs to esters-buliding-blocks, auxiliary class Inhibitor,Natural product, name is Dimethyl fumarate, and the molecular formula is C6H8O4, Quality Control of 624-49-7.

Referemce:
https://en.wikipedia.org/wiki/Ester,
Ester – an overview | ScienceDirect Topics

do Sacramento, Priscila Mendonca published the artcileMajor depression favors the expansion of Th17-like cells and decrease the proportion of CD39+Treg cell subsets in response to myelin antigen in multiple sclerosis patients, Formula: C6H8O4, the publication is Cellular and Molecular Life Sciences (2022), 79(6), 298, database is CAplus and MEDLINE.

Mood disorders have been associated with risk of clin. relapses in multiple sclerosis (MS), a demyelinating disease mediated by myelin-specific T cells. Author aimed to investigate the impact of major depressive disorder (MDD) and cytokine profile of T-cells in relapsing remitting MS patients. For author study, plasma and PBMC were obtained from 60 MS patients (30 with lifetime MDD) in remission phase. The PBMC cultures were stimulated with anti-CD3/anti-CD28 beads or myelin basic protein (MBP), and effector and regulatory T cell phenotypes were determined by flow cytometry. The cytokine levels, both in the plasma or in the supernatants collected from PBMC cultures, were quantified by Luminex. In some experiments, the effect of serotonin (5-HT) was investigated. Here, higher Th17-related cytokine levels in response to anti-CD3/anti-CD28 and MBP were quantified in the plasma and PBMC cultures of the MS/MDD group in comparison with MS patients. Further, elevated frequency of CD4⁺ and CD8⁺ T cells capable of producing IL-17, IL-22 and GM-CSF was observed in depressed patients. Interestingly, the percentage of myelin-specific IFN-γ⁺IL-17⁺ and IFN-γ⁺GM-CSF⁺ CD4⁺ T cells directly correlated with neurol. disabilities. In contrast, the occurrence of MDD reduced the proportion of MBP-specific CD39⁺Tregs subsets. Notably, the severity of both neurol. disorder and depressive symptoms inversely correlated with these Tregs. Finally, the addition of 5-HT downregulated the release of Th17-related cytokines in response to anti-CD3/anti-CD28 and myelin antigen. In summary, author findings suggested that recurrent major depression, by favoring imbalances of effector Th17 and Treg cell subsets, contributes to MS severity.

Cellular and Molecular Life Sciences published new progress about 624-49-7. 624-49-7 belongs to esters-buliding-blocks, auxiliary class Inhibitor,Natural product, name is Dimethyl fumarate, and the molecular formula is C6H8O4, Formula: C6H8O4.

Referemce:
https://en.wikipedia.org/wiki/Ester,
Ester – an overview | ScienceDirect Topics

Bagheri, Farshid published the artcileEffect of dimethyl fumarate on the changes in the medial prefrontal cortex structure and behavior in the poly(I:C)-induced maternal immune activation model of schizophrenia in the male mice, Formula: C6H8O4, the publication is Behavioural Brain Research (2022), 113581, database is CAplus and MEDLINE.

The link between maternal immune activation (MIA) and the risk of developing schizophrenia (SCZ) later in life has been of major focus in recent years. This link could be bridged by activated inflammatory pathways and excessive cytokine release resulting in adverse effects on behavior, histol., and cytoarchitecture. The down-regulatory effects of immunomodulatory agents on the activated glial cells and their therapeutic effects on schizophrenic patients are consistent with this hypothesis. We investigated whether treatment with the anti-inflammatory drug di-Me fumarate (DMF) could rescue impacts of prenatal exposure to polyinosinic:polycytidylic acid [poly (I:C)]. Pregnant dams were administered poly(I:C) at gestational day 9.5. Offspring born from these mothers were treated with DMF for fourteen consecutive days from postnatal day 80 and were assessed behaviorally before and after treatment. The brains were then stained with Cresyl Violet or Golgi-Cox. In addition to the estimation of stereol. parameters, cytoarchitectural changes were also evaluated in the medial prefrontal cortex. MIA caused some abnormalities in behavior, as well as changes in the number of neurons and non-neurons. These alterations were also extended to pyramidal layer III neurons with a significant decrease in dendritic complexity and spine d. which DMF treatment could prevent these changes. Furthermore, DMF treatment was also effective against abnormal exploratory and depression-related behavior, but not the changes in the number of cells. These findings support the idea of using anti-inflammatory agents as adjunctive therapy in patients with SCZ.

Behavioural Brain Research published new progress about 624-49-7. 624-49-7 belongs to esters-buliding-blocks, auxiliary class Inhibitor,Natural product, name is Dimethyl fumarate, and the molecular formula is C6H8O4, Formula: C6H8O4.

Referemce:
https://en.wikipedia.org/wiki/Ester,
Ester – an overview | ScienceDirect Topics

Sainz de la Maza, Susana published the artcileEarly predictive risk factors for dimethyl fumarate-associated lymphopenia in patients with multiple sclerosis, Safety of Dimethyl fumarate, the publication is Multiple Sclerosis and Related Disorders (2022), 103669, database is CAplus and MEDLINE.

Lymphopenia is a major concern in MS patients treated with dimethyl-fumarate (DMF) as it increases the risk of progressive multifocal leukoencephalopathy. A pronounced reduction in absolute lymphocyte counts (ALCs) early after treatment initiation has been suggested to be associated with the occurrence of lymphopenia thereafter. To identify risk factors for DMF-induced lymphopenia and evaluate whether the degree of decrease in the ALCs three months after initiation of DMF treatment is a predictor of the subsequent development of lymphopenia. In this real-world Spanish prospective multicenter study conducted in MS patients who started DMF between 2014 and 2019, we analyzed the association between DMF-related lymphopenia and the percentage of early ALCs decline using regression models, considering both, significant lymphopenia (grades 2 + 3) and severe lymphopenia (grade 3). The cutoff values of early ALCs declines were obtained using the ROC curve. Among 532 MS patients treated with DMF, 193 (36.3%) developed any grade of lymphopenia. Older age and lower ALCs at treatment onset predicted the risk for lymphopenia but the best predictive risk factor was the reduction of ALCs within the three first months of treatment. Specifically, a reduction in ALCs≥21.2% was associated with a 6.5-fold higher risk of developing significant lymphopenia, and a decrease in ALCs≥40.2% with a 12.7-fold higher risk of developing severe lymphopenia. A pronounced reduction in ALCs early after initiation of DMF in MS patients is the best predictive risk factor for the subsequent development of significant lymphopenia.

Multiple Sclerosis and Related Disorders published new progress about 624-49-7. 624-49-7 belongs to esters-buliding-blocks, auxiliary class Inhibitor,Natural product, name is Dimethyl fumarate, and the molecular formula is C6H8O4, Safety of Dimethyl fumarate.

Referemce:
https://en.wikipedia.org/wiki/Ester,
Ester – an overview | ScienceDirect Topics

Pfeuffer, Steffen published the artcileEffectiveness and safety of cladribine in MS: Real-world experience from two tertiary centres, Computed Properties of 624-49-7, the publication is Multiple Sclerosis Journal (2022), 28(2), 257-268, database is CAplus and MEDLINE.

Oral cladribine has been approved for the treatment of relapsing multiple sclerosis (MS) yet real-world evidence regarding its effectiveness and safety remains scarce. To evaluate efficacy and safety outcomes of MS patients following induction of cladribine. We evaluated our prospective cohort of cladribine-treated MS patients from two tertiary centers in Germany. Relapses, disability worsening and occurrence of new or enlarging T2-hyperintense magnetic resonance imaging (MRI) lesions were assessed as well as lymphocyte counts and herpes virus infections. Among 270 patients treated with cladribine, we observed a profound reduction of both relapses and new or enlarging MRI lesions. Treatment appeared more efficacious, especially in patients without previous therapy or following platform substances. Patients switching from natalizumab were prone to re-emerging disease activity. Among patients following di-Me fumarate pre-treatment, severe lymphopenia was common and associated with increased rates of herpes virus manifestations. Overall, we observed an efficacy and safety profile of cladribine consistent with data from the phase 3 clin. trial. However, patients switching from natalizumab experienced suboptimal disease control beyond rebound activity following cessation of natalizumab. Furthermore, di-Me fumarate pre-treatment was associated with a profound risk of developing severe lymphopenia and subsequent herpes virus infections.

Multiple Sclerosis Journal published new progress about 624-49-7. 624-49-7 belongs to esters-buliding-blocks, auxiliary class Inhibitor,Natural product, name is Dimethyl fumarate, and the molecular formula is C6H8O4, Computed Properties of 624-49-7.

Referemce:
https://en.wikipedia.org/wiki/Ester,
Ester – an overview | ScienceDirect Topics

Gudesblatt, Mark published the artcileHealth-Related Quality of Life with Diroximel Fumarate in Patients with Relapsing Forms of Multiple Sclerosis: Findings from Qualitative Research Using Patient Interviews, COA of Formula: C6H8O4, the publication is Advances in Therapy (2022), 39(7), 3199-3213, database is CAplus and MEDLINE.

Abstract: Introduction: Diroximel fumarate (DRF) is an oral fumarate for relapsing multiple sclerosis (MS). Clin. and real-world studies of DRF have demonstrated improved gastrointestinal (GI) tolerability and low (< 1%) GI-related treatment discontinuation vs. di-Me fumarate (DMF) and high rates of treatment adherence. Our aim was to conduct a concept elicitation study to identify treatment-related concepts most meaningful to patients and to evaluate how these concepts shape the patient perspective of DRF. Methods: In-depth qual. interviews were conducted with patients from Oct. to Dec. 2020. US adults who had been prescribed DRF through routine clin. care and had taken DRF for ≥ 3 wk in the past 6 mo were eligible to participate. Semi-structured interviews explored patient perceptions on treatment selection and impact. Results: Seventeen patients participated in the study. Mean (SD) age was 49.3 (12.0) years. Sixteen patients reported prior disease-modifying therapy, while 10 (58.8%) had prior DMF. DRF treatment duration ranged from ∼ 6 wk to 10 mo. Four key concepts emerged: (1) overall wellness and quality of life, (2) ease of administration, (3) minimal and manageable side effects, and (4) patient optimism due to MS treatments. Mode of administration (82.4%), no/mild side effects (70.6%), convenience over injectable/infusion medications (58.8%), and effectiveness (64.7%) were cited as pos. aspects of DRF treatment. Frequent dosing (52.9%) and food requirements (41.2%) were cited as neg. attributes; however, 94.1% had no dietary changes since starting treatment. Conclusion: The patient perspective is a key aspect when considering a disease-modifying therapy for MS, given the multitude of options currently available. Overall wellness, ease of administration, and minimal and manageable side effects were DRF-related concepts most meaningful to patients on therapy. Acknowledging these patient perceptions in shared decision-making may lead to greater patient adherence and optimal treatment outcomes.

Advances in Therapy published new progress about 624-49-7. 624-49-7 belongs to esters-buliding-blocks, auxiliary class Inhibitor,Natural product, name is Dimethyl fumarate, and the molecular formula is C6H8O4, COA of Formula: C6H8O4.

Referemce:
https://en.wikipedia.org/wiki/Ester,
Ester – an overview | ScienceDirect Topics

Wood, Callum H published the artcileIncidence of persistent lymphopenia in people with multiple sclerosis on dimethyl fumarate., Product Details of C6H8O4, the publication is Multiple sclerosis and related disorders (2022), 103492, database is MEDLINE.

BACKGROUND: Dimethyl fumarate (DMF) is a disease modifying therapy (DMT) used in the management of Multiple Sclerosis (MS). Lymphopenia occurs in approximately 30% of people receiving this medication. The recently revised Summary of Product Characteristics (SPC) recommends increased monitoring or cessation of this medication in the context of persistent lymphopenia, because of an increased risk of progressive multifocal leukoencephalopathy (PML). It is therefore important for clinicians and patients to be aware of the frequency of persistent, moderate-severe lymphopenia in order to make informed decisions regarding drug choice and safety monitoring. METHODS: We reviewed medical records of 156 people with MS (PwMS) started on DMF between 2014 and 2020, who received at least 6 months of treatment, in order to identify the incidence and duration of persistent lymphopenia. RESULT: Ten were excluded due to missing data. In 146 patients, treated for 30.7 months (mean), 16 (11%) were found to experience persistent moderate lymphopenia (0.5-0.7 × 10⁹/L) and 5 (3%) experienced persistent severe lymphopenia (<0.5 × 10⁹/L). Of the 5 patients with persistent severe lymphopenia, 3 discontinued DMF. Two cases stopped directly due to SPC recommendations and after 6-months no further DMTs were initiated. Treatment was withdrawn in a further case due to lack of efficacy. Two cases remained on DMF as their persistent severe lymphopenia predated SPC revision. Mean times to persistent moderate and severe lymphopenia were 10.6 months and 25.5 months respectively. Increased age was a predictor for persistent lymphopenia (B = 0.071, p = 0.004) while sex, and previous DMT were not.

Multiple sclerosis and related disorders published new progress about 624-49-7. 624-49-7 belongs to esters-buliding-blocks, auxiliary class Inhibitor,Natural product, name is Dimethyl fumarate, and the molecular formula is C11H14O4, Product Details of C6H8O4.

Referemce:
https://en.wikipedia.org/wiki/Ester,
Ester – an overview | ScienceDirect Topics

Pinto, Barbara Fernandes published the artcileInhalation of dimethyl fumarate-encapsulated solid lipid nanoparticles attenuate clinical signs of experimental autoimmune encephalomyelitis and pulmonary inflammatory dysfunction in mice, Quality Control of 624-49-7, the publication is Clinical Science (2022), 136(1), 81-101, database is CAplus and MEDLINE.

The FDA-approved Di-Me Fumarate (DMF) as an oral drug for Multiple Sclerosis (MS) treatment based on its immunomodulatory activities. However, it also caused severe adverse effects mainly related to the gastrointestinal system. Investigated the potential effects of solid lipid nanoparticles (SLNs) containing DMF, administered by inhalation on the clin. signs, central nervous system (CNS) inflammatory response, and lung function changes in mice with exptl. autoimmune encephalomyelitis (EAE). EAE was induced using MOG35-55 peptide in female C57BL/6J mice and the mice were treated via inhalation with DMF-encapsulated SLN (CTRL/SLN/DMF and EAE/SLN/DMF), empty SLN (CTRL/SLN and EAE/SLN), or saline solution (CTRL/saline and EAE/saline), every 72 h during 21 days. After 21 days post-induction, EAE mice treated with DMF-loaded SLN, when compared with EAE/saline and EAE/SLN, showed decreased clin. score and weight loss, reduction in brain and spinal cord injury and inflammation, also related to the increased influx of Foxp3+ cells into the spinal cord and lung tissues. Moreover, our data revealed that EAE mice showed signs of respiratory disease, marked by increased vascular permeability, leukocyte influx, production of TNF-a and IL-17, perivascular and peribronchial inflammation, with pulmonary mech. dysfunction associated with loss of respiratory volumes and elasticity, which DMF-encapsulated reverted in SLN nebulization. Our study suggests that inhalation of DMF-encapsulated SLN is an effective therapeutic protocol that reduces not only the CNS inflammatory process and disability progression, characteristic of EAE disease, but also protects mice from lung inflammation and pulmonary dysfunction.

Clinical Science published new progress about 624-49-7. 624-49-7 belongs to esters-buliding-blocks, auxiliary class Inhibitor,Natural product, name is Dimethyl fumarate, and the molecular formula is C6H8O4, Quality Control of 624-49-7.

Referemce:
https://en.wikipedia.org/wiki/Ester,
Ester – an overview | ScienceDirect Topics

Tran, Huy published the artcileDivergent and Modular Synthesis of Terpenoid Scaffolds via a Au^I Catalyzed One-Pot Cascade, SDS of cas: 624-49-7, the publication is Angewandte Chemie, International Edition (2022), 61(1), e202110575, database is CAplus and MEDLINE.

A one-pot cascade sequence to generate synthetically challenging polycyclic scaffolds is reported utilizing a novel Lewis acid gold catalyst for the key cyclization step, enabling the divergent synthesis of both 6,6,5-tricyclic and 6,6,6,5-tetracyclic cores through both ligand and reaction condition control. We have combined the intrinsic complexity and stereoselectivity of cycloadditions with the electronic and steric properties of gold complexes to selectively generate complex polycyclic scaffolds in a single operation.

Angewandte Chemie, International Edition published new progress about 624-49-7. 624-49-7 belongs to esters-buliding-blocks, auxiliary class Inhibitor,Natural product, name is Dimethyl fumarate, and the molecular formula is C5H9IO2, SDS of cas: 624-49-7.

Referemce:
https://en.wikipedia.org/wiki/Ester,
Ester – an overview | ScienceDirect Topics