Category: 624-49-7

Rauma, Ilkka published the artcileSafety of alemtuzumab in a nationwide cohort of Finnish multiple sclerosis patients, Application of Dimethyl fumarate, the publication is Journal of Neurology (2022), 269(2), 824-835, database is CAplus and MEDLINE.

Alemtuzumab is an effective disease-modifying therapy (DMT) for highly active multiple sclerosis (MS). However, safety concerns limit its use in clin. practice. To evaluate the safety of alemtuzumab in a nationwide cohort of Finnish MS patients. In this retrospective case series study, we analyzed the data of all but two MS patients who had received alemtuzumab in Finland until 2019. Data were systematically collected from patient files. Altogether 121 patients were identified, most of whom had received previous DMTs (82.6%). Median follow-up time after treatment initiation was 30.3 mo and exceeded 24 mo in 78 patients. Infusion-associated reactions (IARs) were observed in 84.3%, 57.3%, and 57.1% of patients during alemtuzumab courses 1-3, resp. Serious adverse events (SAEs) were observed in 32.2% of patients, serious IARs in 12.4% of patients, and SAEs other than IARs in 23.1% of patients. Autoimmune adverse events were observed in 30.6% of patients. One patient died of hemophagocytic lymphohistiocytosis, and one patient died of pneumonia. A previously unreported case of thrombotic thrombocytopenic purpura was documented. SAEs were more frequent in the present cohort than in previous studies. Even though alemtuzumab is a highly effective therapy for MS, vigorous monitoring with a long enough follow-up time is advised.

Journal of Neurology 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, Application of Dimethyl fumarate.

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

Suhrkamp, Ina published the artcileOral Dimethyl Fumarate Targets HCA2-Expressing Skin Cells in the Imiquimod Mouse Model, SDS of cas: 624-49-7, the publication is Journal of Investigative Dermatology (2022), 142(9), 2547-2550.e5, database is CAplus and MEDLINE.

Fumarates (fumaric acid esters, FAEs) are orally administered systemic agents used for the treatment of psoriasis and multiple sclerosis. DMF therapy typically improves skin inflammation within the first 3 mo of treatment. The aim of this study was to evaluate pharmacokinetic parameters of fumaric acid esters (FAE) in psoriasis patients for the first time. Flow cytometry was used to assess T-cell and neutrophil frequencies, apoptosis and activation phenotype. Our results reveal a novel in vivo effect of DMF therapy on pro-inflammatory neutrophils that likely contributes to this treatments antipsoriatic efficacy.

Journal of Investigative Dermatology 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 C15H14O3, SDS of cas: 624-49-7.

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

Dreyer-Alster, Sapir published the artcileCOVID-19 vaccination in patients with multiple sclerosis: Safety and humoral efficacy of the third booster dose, Related Products of esters-buliding-blocks, the publication is Journal of the Neurological Sciences (2022), 120155, database is CAplus and MEDLINE.

As immunity against SARS-COV-2 wanes following first and second doses of vaccination, a third dose is administered in several countries around the world. Similarly to the first doses, risks related to vaccination and humoral immune response in patients with multiple sclerosis (MS) need to be assessed. Characterize safety and humoral immune response following the third dose of COVID-19 vaccination in a large cohort of MS patients. We assessed the safety of the third dose of the BNT162b2-COVID-19 mRNA vaccination in adult MS patients and evaluated SARS-CoV-2 IgG response. Two hundred and eleven adult MS patients received a third dose of BNT162b2 COVID-19 vaccination. Median follow up time was 66 days from vaccine administration (IQR 54-84). The frequency of any adverse event was 54.5%, with the most common reported adverse events being fatigue, local pain at the injection site, fever and muscle or joint pain. Transient increase in MS symptoms was reported in 3.8% of patients, none of them requiring treatment. The rate of acute relapses treated with IV steroids was 3.3%. In a sub-group of 55 patients, 20 untreated and 35 treated with vaccination-safe disease-modifying treatments, SARS-CoV-2 IgG levels increased 21-fold (median ± SD 21.6 ± 53.05). The third dose of COVID-19-BNT162b2 vaccine proved safe for MS patients, with no increased risk of relapse activity. Untreated patients and patients treated with vaccination-safe disease-modifying treatments show significant increase in SARS-CoV-2 IgG levels following the third dose of vaccination.

Journal of the Neurological 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, Related Products of esters-buliding-blocks.

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

Borrelli, S. published the artcileDelayed and recurrent dimethyl fumarate induced-lymphopenia in patients with multiple sclerosis, HPLC of Formula: 624-49-7, the publication is Multiple Sclerosis and Related Disorders (2022), 103887, database is CAplus and MEDLINE.

Early lymphopenia is a known side effect of di-Me fumarate, a disease-modifying therapy for MS. However, the long-term effects on immune response and the impact on lymphocyte counts when another disease-modifying treatment is introduced, remain unknown. To better understand these specific aspects, we reviewed cases that develop prolonged grade 2 to 4 lymphopenia under di-Me fumarate in Lausanne MS clinic. Retrospective anal. of the 12 patients (10.1%) who discontinued di-Me fumarate because of prolonged lymphopenia amongst the 119 patients treated with di-Me fumarate. We reviewed their demographics, as well as their clin., biol. and MRI characteristics compared to the non-lymphopenic patients, during di-Me fumarate therapy, and within a timeframe of up to 18 mo after switching to another disease-modifying treatment. We also focused on lymphocyte subsets in a subgroup of patients. Compared to non-lymphopenic patients, lymphopenic patients were older at di-Me fumarate initiation (51.4 yo vs 39.7, p = 0.0003) and the majority were male (p = 0.037). Three of them (25%) developed delayed lymphopenia, more than one year after treatment onset. Despite persistent lymphopenia, three patients experienced disease activity. Amongst the nine patients (75%) who were switched to another therapy, five (55.6%) presented recurrent lymphopenia, predominantly with a CD8⁺ T cell decrease. Di-Me fumarate has a long-term impact on lymphocyte biol., even after its discontinuation, with a sustained reduction in CD8+ T cells that may increase opportunistic infection risk, and should be taken in consideration when switching therapies after di-Me fumarate.

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, HPLC of Formula: 624-49-7.

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

Tata, Alessandra published the artcileAmbient mass spectrometry for rapid authentication of milk from Alpine or lowland forage, Safety of Dimethyl fumarate, the publication is Scientific Reports (2022), 12(1), 7360, database is CAplus and MEDLINE.

Metabolomics approaches, such as direct anal. in real time-high resolution mass spectrometry (DART-HRMS), allow characterizing many polar and non-polar compounds useful as authentication biomarkers of dairy chains. By using both a partial least squares discriminant anal. (PLS-DA) and a linear discriminant anal. (LDA), this study aimed to assess the capability of DART-HRMS, coupled with a low-level data fusion, discriminate among milk samples from lowland (silages vs. hay) and Alpine (grazing; APS) systems and identify the most informative biomarkers associated with the main dietary forage. As confirmed also by the LDA performed against the test set, DART-HRMS anal. provided an accurate discrimination of Alpine samples; meanwhile, there was a limited capacity to correctly recognize silage- vs. hay-milks. Supervised multivariate statistics followed by metabolomics hierarchical cluster anal. allowed extrapolating the most significant metabolites. Lowland milk was characterised by a pool of energetic compounds, ketoacid derivates, amines and organic acids. Seven informative DART-HRMS mol. features, mainly monoacylglycerols, could strongly explain the metabolomic variation of Alpine grazing milk and contributed to its classification. The misclassification between the two lowland groups confirmed that the intensive dairy systems would be characterised by a small variation in milk composition

Scientific Reports 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 C40H35N7O8, Safety of Dimethyl fumarate.

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

Das, Sanjib Kumar published the artcileIdentification of phytocompounds from Houttuynia cordata Thunb. as potential inhibitors for SARS-CoV-2 replication proteins through GC-MS/LC-MS characterization, molecular docking and molecular dynamics simulation, Application In Synthesis of 624-49-7, the publication is Molecular Diversity (2022), 26(1), 365-388, database is CAplus and MEDLINE.

The COVID-19 pandemic caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a massive viral disease outbreak of international concerns. The present study is mainly intended to identify the bioactive phytocompounds from traditional antiviral herb Houttuynia cordata Thunb. as potential inhibitors for three main replication proteins of SARS-CoV-2, namely Main protease (Mpro), Papain-Like protease (PLpro) and ADP ribose phosphatase (ADRP) which control the replication process. A total of 177 phytocompounds were characterized from H. cordata using GC-MS/LC-MS and they were docked against three SARS-CoV-2 proteins (receptors), namely Mpro, PLpro and ADRP using Epic, LigPrep and Glide module of Schrodinger suite 2020-3. During docking studies, phytocompounds (ligand) 6-Hydroxyondansetron (A104) have demonstrated strong binding affinity toward receptors Mpro (PDB ID 6LU7) and PLpro (PDB ID 7JRN) with G-score of – 7.274 and – 5.672, resp., while Quercitrin (A166) also showed strong binding affinity toward ADRP (PDB ID 6W02) with G-score -6.788. Mol. Dynamics Simulation (MDS) performed using Desmond module of Schrodinger suite 2020-3 has demonstrated better stability in the ligand-receptor complexes A104-6LU7 and A166-6W02 within 100 ns than the A104-7JRN complex. The ADME-Tox study performed using SwissADMEserver for pharmacokinetics of the selected phytocompounds 6-Hydroxyondansetron (A104) and Quercitrin (A166) demonstrated that 6-Hydroxyondansetron passes all the required drug discovery rules which can potentially inhibit Mpro and PLpro of SARS-CoV-2 without causing toxicity while Quercitrin demonstrated less drug-like properties but also demonstrated as potential inhibitor for ADRP. Present findings confer opportunities for 6-Hydroxyondansetron and Quercitrin to be developed as new therapeutic drug against COVID-19.

Molecular Diversity 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, Application In Synthesis of 624-49-7.

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

Smith, Tyler E. published the artcileRisk of COVID-19 infection and severe disease in MS patients on different disease-modifying therapies, Formula: C6H8O4, the publication is Multiple Sclerosis and Related Disorders (2022), 103735, database is CAplus and MEDLINE.

The risk of SARS-CoV-2 infection and severity with disease modifying therapies (DMTs) in multiple sclerosis (MS) remains unclear, with some studies demonstrating increased risks of infection with B-cell-depleting (anti-CD20) therapies and severity, while others fail to observe an association Most existing studies are limited by a reliance on ′numerator′ data (i.e., COVID-19 cases) only. To assess the risks of COVID-19 by DMT, this study aimed to assess both ′numerator′ (patients with SARS-CoV-2 infection) and ′denominator′ data (all patients treated with DMTs of interest) to determine if any DMTs impart an increased risk of SARS-CoV-2 infection or disease severity. We systematically reviewed charts and queried patients during clinic encounters in the NYU MS Comprehensive Care Center (MSCCC) for evidence of COVID-19 in all patients who were on the most commonly used DMTs in our clinic (sphingosine-1-phosphate receptor (S1P) modulators (fingolimod/siponimod), rituximab, ocrelizumab, fumarates (di-Me fumarate/diroximel fumarate), and natalizumab). COVID-19 status was determined by clin. symptoms (CDC case definition) and laboratory testing where available (SARS-CoV-2 PCR, SARS-CoV-2 IgG). Multivariable analyses were conducted to determine predictors of infection and severe disease (hospitalization or death) using SARS-CoV-2 infected individuals per DMT group and all individuals on a given DMT as denominator. We identified 1,439 MS patients on DMTs of interest, of which 230 had lab-confirmed (n = 173; 75.2%) or suspected (n = 57; 24.8%) COVID-19. Infection was most frequent in those on rituximab (35/138; 25.4%), followed by fumarates (39/217; 18.0%), S1P modulators (43/250; 17.2%), natalizumab (36/245; 14.7%), and ocrelizumab (77/589; 13.1%). There were 14 hospitalizations and 2 deaths. No DMT was found to be significantly associated with increased risk of SARS-CoV-2 infection. Rituximab was a predictor of severe SARS-CoV-2 infection among patients with SARS-CoV-2 infection (OR 6.7; 95% CI 1.1-41.7) but did not reach statistical significance when the entire patient population on DMT was used (OR 2.8; 95% CI 0.6-12.2). No other DMT was associated with an increased risk of severe COVID-19. Anal. of COVID-19 risk among all patients on the commonly used DMTs did not demonstrate increased risk of infection with any DMT. Rituximab was associated with increased risk for severe disease.

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 C11H22N2O4, Formula: C6H8O4.

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

Iaffaldano, Pietro published the artcileRisk of Getting COVID-19 in People With Multiple Sclerosis: A Case-Control Study., Category: esters-buliding-blocks, the publication is Neurology(R) neuroimmunology & neuroinflammation (2022), 9(2), database is MEDLINE.

BACKGROUND AND OBJECTIVES: Several studies have assessed risk factors associated with the severity of COVID-19 outcomes in people with multiple sclerosis (PwMS). The potential role of disease-modifying therapies (DMTs) and demographic and clinical factors on the risk of acquiring SARS-CoV-2 infection has not been evaluated so far. The objective of this study was to assess risk factors of contracting SARS-CoV-2 infection in PwMS by using data collected in the Italian MS Register (IMSR). METHODS: A case-control (1:2) study was set up. Cases included PwMS with a confirmed diagnosis of COVID-19, and controls included PwMS without a confirmed diagnosis of COVID-19. Both groups were propensity score-matched by the date of COVID-19 diagnosis, the date of last visit, and the region of residence. No healthy controls were included in this study. COVID-19 risk was estimated by multivariable logistic regression models including demographic and clinical covariates. The impact of DMTs was assessed in 3 independent logistic regression models including one of the following covariates: last administered DMT, previous DMT sequences, or the place where the last treatment was administered. RESULTS: A total of 779 PwMS with confirmed COVID-19 (cases) were matched to 1,558 PwMS without COVID-19 (controls). In all 3 models, comorbidities, female sex, and a younger age were significantly associated (p < 0.02) with a higher risk of contracting COVID-19. Patients receiving natalizumab as last DMT (OR [95% CI]: 2.38 [1.66-3.42], p < 0.0001) and those who underwent an escalation treatment strategy (1.57 [1.16-2.13], p = 0.003) were at significantly higher COVID-19 risk. Moreover, PwMS receiving their last DMT requiring hospital access (1.65 [1.34-2.04], p < 0.0001) showed a significant higher risk than those taking self-administered DMTs at home. DISCUSSION: This case-control study embedded in the IMSR showed that PwMS at higher COVID-19 risk are younger, more frequently female individuals, and with comorbidities. Long-lasting escalation approach and last therapies that expose patients to the hospital environment seem to significantly increase the risk of SARS-CoV2 infection in PwMS. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that among patients with MS, younger age, being female individuals, having more comorbidities, receiving natalizumab, undergoing an escalating treatment strategy, or receiving treatment at a hospital were associated with being infected with COVID-19. Among patients with MS who were infected with COVID-19, a severe course was associated with increasing age and having a progressive form of MS, whereas not being on treatment or receiving an interferon beta agent was protective.

Neurology(R) neuroimmunology & neuroinflammation 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, Category: esters-buliding-blocks.

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

de Souza, Alana Gomes published the artcileNeuroprotective effects of dimethyl fumarate against depression-like behaviors via astrocytes and microglia modulation in mice: possible involvement of the HCAR2/Nrf2 signaling pathway, Application of Dimethyl fumarate, the publication is Naunyn-Schmiedeberg’s Archives of Pharmacology, database is CAplus and MEDLINE.

We postulated that di-Me fumarate (DMF) exerts neuroprotective effects against depression-like behaviors through astrocytes and microglia modulation. To ascertain our hypothesis and define the mechanistic pathways involved in effect of DMF on neuroinflammation, we used the depression model induced by chronic unpredictable mild stress (CUMS), in which, the mice were exposed to stressful events for 28 days and from the 14th day they received DMF in the doses of 50 and 100 mg/kg or fluoxetine 10 mg/kg or saline. On the 29th day, the animals were subjected to behavioral tests. Microglia (Iba1) and astrocyte (GFAP) marker expressions were evaluated by immunofluorescence analyzes and the cytokines TNF-α and IL-Iβ by immunoenzymic assay. In addition, computational target prediction, 3D protein structure prediction, and docking calculations were performed with monomethyl fumarate (DMF active metabolite) and the Keap1 and HCAR2 proteins, which suggested that these could be the probable targets related protective effects. CUMS induced anxiety- and depressive-like behaviors, cognitive deficit, decreased GFAP, and increased Iba1, TNF-α, and IL-Iβ expression in the hippocampus. These alterations were reversed by DMF. Thus, it is suggested that one of the mechanisms involved in the antidepressant effect of DMF is neuroinflammatory suppression, through the signaling pathway HCAR2/Nrf2. However, more studies must be performed to better understand the mol. mechanisms of this drug.

Naunyn-Schmiedeberg’s Archives of Pharmacology 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, Application of Dimethyl fumarate.

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

Sun, Zikai published the artcileImmunosuppressive effects of dimethyl fumarate on dendritic cell maturation and migration: a potent protector for coronary heart disease, Recommanded Product: Dimethyl fumarate, the publication is Immunopharmacology and Immunotoxicology (2022), 44(2), 178-185, database is CAplus and MEDLINE.

Dendritic cells (DCs), as a bridge between innate and adaptive immunity, play key roles in atherogenesis, particularly in plaque rupture, the underlying pathophysiol. cause of myocardial infarction. Targeting DC functions, including maturation and migration to atherosclerotic plaques, may be a novel therapeutic approach to atherosclerotic disease. Di-Me fumarate (DMF), an agent consisting of a combination of fumaric acid esters, in current study were found to be able to suppress DC maturation by reducing the expression of costimulatory mols. and MHC class II and by blocking cytokine secretion. In addition, DMF efficiently inhibited the migration of activated DCs in vitro and in vivo by reducing the expression of chemokine receptor 7 (CCR7). Addnl., DMF efficiently inhibited the expression of the costimulatory mol. CD86, as well as the chemokine receptor CCR7 and the C-XC motif chemokine receptor 4 (CXCR4), in healthy donor-derived purified DCs that had been stimulated by ST-segment elevation myocardial infarction (STEMI) patient serum. This study points to the potent therapeutic value of DMF for protecting against cardiovascular disease by suppressing DC functions.

Immunopharmacology and Immunotoxicology 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 C25H29N9O3, Recommanded Product: Dimethyl fumarate.

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