Category: 624-49-7

Rupp, Tristan published the artcileTherapeutic Potential of Fingolimod and Dimethyl Fumarate in Non-Small Cell Lung Cancer Preclinical Models., SDS of cas: 624-49-7, the publication is International journal of molecular sciences (2022), 23(15), database is MEDLINE.

New therapies are required for patients with non-small cell lung cancer (NSCLC) for which the current standards of care poorly affect the patient prognosis of this aggressive cancer subtype. In this preclinical study, we aim to investigate the efficacy of Fingolimod, a described inhibitor of sphingosine-1-phosphate (S1P)/S1P receptors axis, and Dimethyl Fumarate (DMF), a methyl ester of fumaric acid, both already approved as immunomodulators in auto-immune diseases with additional expected anti-cancer effects. The impact of both drugs was analyzed with in vitro cell survival analysis and in vivo graft models using mouse and human NSCLC cells implanted in immunocompetent or immunodeficient mice, respectively. We demonstrated that Fingolimod and DMF repressed tumor progression without apparent adverse effects in vivo in three preclinical mouse NSCLC models. In vitro, Fingolimod did not affect either the tumor proliferation or the cytotoxicity, although DMF reduced tumor cell proliferation. These results suggest that Fingolimod and DMF affected tumor progression through different cellular mechanisms within the tumor microenvironment. Fingolimod and DMF might uncover potential therapeutic opportunities in NSCLC.

International journal of molecular 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, SDS of cas: 624-49-7.

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

Calow, Adam D. J. published the artcileCarbonylative N-Heterocyclization via Nitrogen-Directed C-C Bond Activation of Nonactivated Cyclopropanes, Application of Dimethyl fumarate, the publication is Journal of the American Chemical Society (2022), 144(25), 11069-11074, database is CAplus and MEDLINE.

Under Rh-catalyzed conditions, secondary amines and anilines function as directing groups to facilitate regioselective C-C bond activation of nonactivated cyclopropanes. The resulting amino-stabilized rhodacycles underwent carbonylative C-N bond formation en route to challenging seven- and eight-membered lactams. The processes represented rare examples where C-C bond oxidative addition of nonactivated cyclopropanes is exploited in reaction design.

Journal of the American Chemical Society 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

Zhang, Wei published the artcileHighly Reactive Cyclic Carbonates with a Fused Ring toward Functionalizable and Recyclable Polycarbonates, Recommanded Product: Dimethyl fumarate, the publication is ACS Macro Letters (2022), 11(2), 173-178, database is CAplus and MEDLINE.

Monomer design plays an important role in the development of polymers with desired thermal properties and chem. recyclability. Here we prepared a class of seven-membered ring carbonates containing trans-cyclohexyl fused rings. These monomers showed excellent activity for ring-opening polymerization (ROP) with turnover frequency (TOF) up to 6 x 10⁵ h^-1 and catalyst loading down to 50 ppm, which yielded high-mol.-weight polycarbonates (M_n up to 673 kg/mol) with great thermostability (T_d > 300°C). Ultimately, the resulting polycarbonates can completely depolymerize into their corresponding cyclic dimers that can repolymerize to synthesize the starting polymers in moderate yields, demonstrating a potential route to achieve chem. recycling. Post-functionalization of the unsaturated polycarbonate was conducted through crosslinking reaction and “click” reaction under UV irradiation

ACS Macro Letters 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 C8H7ClO3, Recommanded Product: Dimethyl fumarate.

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

Sauerland, Max B. published the artcileElectrophile versus oxidant modification of cysteine residues: Kinetics as a key driver of protein modification, Application of Dimethyl fumarate, the publication is Archives of Biochemistry and Biophysics (2022), 109344, database is CAplus and MEDLINE.

A review. Humans have widespread exposure to both oxidants, and soft electrophilic compounds such as alpha,beta-unsaturated aldehydes and quinones. Electrophilic motifs are commonly found in a drugs, industrial chems., pollutants and are also generated via oxidant-mediated degradation of biomols. including lipids (e.g. formation of 4-hydroxynonenal, 4-hydroxyhexenal, prostaglandin J2). All of these classes of compounds react efficiently with Cys residues, and the particularly the thiolate anion, with this resulting in Cys modification via either oxidation or adduct formation. This can result in deleterious or beneficial effects, that are either reversible (e.g. in cell signalling) or irreversible (damaging). For example, acrolein is a well-established toxin, whereas dimethylfumarate is used in the treatment of multiple sclerosis and psoriasis. This short review discusses the targets of alpha,beta-unsaturated aldehydes, and particularly two prototypic cases, acrolein and dimethylfumarate, and the factors that control the selectivity and kinetics of reaction of these species. Comparison is made between the reactivity of oxidants vs. soft electrophiles. These rate constants indicate that electrophiles can be significant thiol modifying agents in some situations, as they have rate constants similar to or greater than species such as H2O2, can be present at higher concentrations, and are less efficiently removed by protective systems when compared to H2O2. They may also induce similar or higher levels of modification than highly reactive oxidants, due to the very low concentrations of oxidants formed in most in vivo situations.

Archives of Biochemistry and Biophysics 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

Kamma, Emily published the artcileCentral nervous system macrophages in progressive multiple sclerosis: relationship to neurodegeneration and therapeutics, Product Details of C6H8O4, the publication is Journal of Neuroinflammation (2022), 19(1), 45, database is CAplus and MEDLINE.

A review. There are over 15 disease-modifying drugs that have been approved over the last 20 years for the treatment of relapsing-remitting multiple sclerosis (MS), but there are limited treatment options available for progressive MS. The development of new drugs for the treatment of progressive MS remains challenging as the pathophysiol. of progressive MS is poorly understood. The progressive phase of MS is dominated by neurodegeneration and a heightened innate immune response with trapped immune cells behind a closed blood-brain barrier in the central nervous system. Here we review microglia and border-associated macrophages, which include perivascular, meningeal, and choroid plexus macrophages, during the progressive phase of MS. These cells are vital and are largely the basis to define lesion types in MS. We will review the evidence that reactive microglia and macrophages upregulate pro-inflammatory genes and downregulate homeostatic genes, that may promote neurodegeneration in progressive MS. We will also review the factors that regulate microglia and macrophage function during progressive MS, as well as potential toxic functions of these cells. Disease-modifying drugs that solely target microglia and macrophage in progressive MS are lacking. The recent treatment successes for progressive MS include include B-cell depletion therapies and sphingosine-1-phosphate receptor modulators. We will describe several therapies being evaluated as a potential treatment option for progressive MS, such as immunomodulatory therapies that can target myeloid cells or as a potential neuroprotective agent.

Journal of 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, Product Details of C6H8O4.

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

Schulte, Bianca published the artcileAndrographolide Derivatives Target the KEAP1/NRF2 Axis and Possess Potent Anti-SARS-CoV-2 Activity, SDS of cas: 624-49-7, the publication is ChemMedChem (2022), 17(5), e202100732, database is CAplus and MEDLINE.

Naturally occurring compounds represent a vast pool of pharmacol. active entities. One of such compounds is andrographolide, which is endowed with many beneficial properties, including the activity against SARS-CoV-2. To initiate a drug repurposing or hit optimization campaign, it is imperative to unravel the primary mechanism(s) of the antiviral action of andrographolide. We showed by means of a reporter gene assay that andrographolide exerts its anti-SARS-CoV-2 effects by inhibiting the interaction between Kelch-like ECH-associated protein 1 (KEAP1) and nuclear factor erythroid 2-related factor 2 (NRF2) causing NRF2 upregulation. Moreover, we demonstrated that subtle structural modifications of andrographolide could lead to derivatives with stronger on-target activities and improved physicochem. properties. Our results indicate that further optimization of this structural class is warranted to develop novel COVID-19 therapies.

ChemMedChem 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 C14H10O4, SDS of cas: 624-49-7.

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

Bossart, Jonas published the artcileReal-world disease-modifying therapy usage in persons with relapsing-remitting multiple sclerosis: Cross-sectional data from the Swiss Multiple Sclerosis Registry, Quality Control of 624-49-7, the publication is Multiple Sclerosis and Related Disorders (2022), 103706, database is CAplus and MEDLINE.

Several disease-modifying therapies (DMTs), covering a broad spectrum of mechanisms of action, have been approved by regulatory agencies for the treatment of relapsing-remitting multiple sclerosis (RRMS). However, only little is known about the current real-world treatment situation in Switzerland. Based on data from a diverse population of 668 persons with RRMS from the Swiss Multiple Sclerosis Registry (SMSR), the present study aims to fill this gap with a descriptive, cross-sectional approach. Data originated from the SMSR baseline questionnaire and follow-up surveys. Data on current health status and life situation in the last 6 mo were extracted from the survey distributed throughout 2020 and 2021, while data on disease-modifying therapy (DMT) histories were included from preceding surveys. Initially, data was stratified into three DMT groups according to the current DMT status (NO (No DMT), CONTINUED (DMT started more than 6 mo ago), and NEW (DMT started less than 6 mo ago)). In a subsequent anal., the sample was stratified into groups corresponding to the five most frequently prescribed DMTs. Self-reported outcomes including therapy discontinuation or interruption, relapses and side-effects in the last 6 mo were analyzed per group. Life and health situation parameters were also determined and analyzed. The study population consisted of 445 (66.6%) individuals belonging to the CONTINUED, 84 (12.6%) to the NEW, and 139 (20.8%) to the NO group. Within the NO group, 24 (17.3%) reported relapses. Furthermore, self-reported relapses (28 (33.3%)), side-effects (39 (46.4%)), and treatment discontinuations or interruptions (30 (35.7%)) occurred more frequently in the NEW compared to the CONTINUED group (37 (8.3%), 125 (28.1%), 8 (1.8%), resp.). The three groups also differed with respect to age, time since diagnosis, number of symptoms, DMT history, and health-related quality of life. The five most frequently prescribed DMTs included fingolimod (33.4%), di-Me fumarate (25.0%), ocrelizumab (23.6%), natalizumab (10.6%) and teriflunomide (7.5%). The frequency of self-reported relapses ranged from 9.7% to 13.6%. Notable differences were found in the number of self-reported side-effects, ranging from 9.1% with natalizumab to 56.7% with di-Me fumarate. This cross-sectional anal. suggested that the majority of individuals with RRMS in Switzerland continuously receive tolerable DMT. However, groups not receiving DMT or struggling with side-effects or continued disease worsening while on DMT still persist. It is conceivable that the number of self-reported symptoms indicates the need for more detailed clarification of the DMT characteristics and expectations of treatment outcomes. Injectable DMTs no longer play a major role in the treatment of RRMS in Switzerland and a trend toward an early use of potent drugs is emerging.

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, Quality Control of 624-49-7.

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

Bock, H. published the artcileHumoral and cellular immune responses to SARS CoV-2 vaccination in People with Multiple Sclerosis and NMOSD patients receiving immunomodulatory treatments, Application In Synthesis of 624-49-7, the publication is Multiple Sclerosis and Related Disorders (2022), 103554, database is CAplus and MEDLINE.

Vaccination against SARS CoV-2 results in excellent personal protection against a severe course of COVID-19. In People with Multiple Sclerosis (PwMS) vaccination efficacy may be reduced by immunomodulatory medications. To assess the vaccination induced cellular and humoral immune response in PwMS receiving disease modifying therapies. In a monocentric observational study on PwMS and patients with Neuromyelitis optica we quantified the cellular and humoral immune responses to SARS CoV-2. PwMS receiving glatiramer acetate, Interferon-ss, Dimethylfumarate, Cladribine or Natalizumab had intact humoral and cellular immune responses following vaccination against SARS CoV-2. B-cell depleting therapies reduced B-cell responses but did not affect T cell responses. Sphingosin-1-Phospate (S1P) inhibitors strongly reduced humoral and cellular immune responses. There was a good agreement between the Interferon gamma release assay and the T-SPOT assay used to measure viral antigen induced T-cell responses. This study demonstrates that S1P inhibitors impair the cellular and humoral immune response in SARS CoV-2 vaccination, whereas patients receiving B-cell depleting therapies mount an intact cellular immune response. These data can support clinicians in counselling their PwMS and NMOSD patients during the COVID 19 pandemic.

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, Application In Synthesis of 624-49-7.

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

Dwivedi, Durgesh Kumar published the artcileSimultaneous Modulation of NLRP3 Inflammasome and Nrf2/ARE Pathway Rescues Thioacetamide-Induced Hepatic Damage in Mice: Role of Oxidative Stress and Inflammation, COA of Formula: C6H8O4, the publication is Inflammation (2022), 45(2), 610-626, database is CAplus and MEDLINE.

Chronic tissue injury resulting in fibrosis of multiple organs, responsible for one-third of the death globally. Liver fibrosis is a common pathway/condition involved in all chronic liver diseases. Thioacetamide (TAA), a hepatotoxicant, was used to induce hepatic fibrosis. Anti-diabetic drug glibenclamide (GLB) possesses anti-inflammatory properties and inhibits NACHT, LRR, and PYD domains-containing protein 3 (NLRP3) inflammasome activation. Di-Me fumarate (DMF), a multiple sclerosis drug, activates the nuclear factor erythroid 2-related factor 2 (Nrf2)/antioxidant response element (ARE) pathway and maintains the antioxidant status in the cell. The present study was designed to investigate (i) role of NLRP3 inflammasome and Nrf2/ARE pathway in TAA-induced hepatotoxicity and liver fibrosis, (ii) mechanism involved in GLB and DMF mediated hepatoprotection against TAA-induced hepatotoxicity, and (iii) addnl./synergistic hepatoprotective effect of combination treatment with NLRP3 inhibition + Nrf2 activation or GLB + DMF or MCC950 + 4OI to reverse/ameliorate the exptl. liver fibrosis completely. TAA was administered i.p. to mice for seven consecutive weeks, and treatments of GLB, DMF, GLB + DMF, MCC950, 4OI, and MCC950 + 4OI were provided for the last three consecutive weeks. The intervention with GLB, DMF, GLB + DMF, MCC950, 4OI, and MCC950 + 4OI significantly protected TAA-induced oxidative stress and inflammatory conditions by improving biochem., histol., and immunoexpression changes in mice. The GLB, DMF, and GLB + DMF intervention exhibited a better protective effect compared with MCC950, 4OI, and MCC950 + 4OI, which revealed that this specific inhibitor/activator possesses only NLRP3 inflammasome inhibitory/Nrf2 activatory properties. In contrast, the clin. drug GLB and DMF have several other beneficial effects, which are independent of NLRP3 inhibition and Nrf2 activation.

Inflammation 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

Umemoto, Nao published the artcileDevelopment of regioselective [2 + 3] cycloaddition reactions of nitrile oxides with alkenes using intramolecular reactions through oxime groups [1], Recommanded Product: Dimethyl fumarate, the publication is Tetrahedron (2022), 132833, database is CAplus.

Nitrile oxides afford 2-isoxazoline heterocycles through [2 + 3] cycloaddition reactions with alkenes. These heterocycles can be converted to useful intermediates, such as β-hydroxy ketones and γ-amino alcs., leading to pharmaceutical and agrochem. compounds However, nitrile oxides directly connected to a carbonyl group show low reactivity owing to the decrease in energy of the dipole HOMO. Furthermore, when dissym. internal alkenes are used, regioselective control is difficult. Herein, authors have designed nitrile oxides bound to alkenes through the oxime group and demonstrated their intramol. [2 + 3] cycloaddition reactions. The desired cycloadducts were obtained in high yields and as single regioisomers. Furthermore, face-selective cycloaddition reactions were achieved by introducing a stereocenter into the linker moiety, affording the desired cycloadducts with good diastereoselectivity.

Tetrahedron 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 C12H23N3S, Recommanded Product: Dimethyl fumarate.

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