Month: November 2022

Pryde, David C.; Middya, Sandip; Banerjee, Monali; Shrivastava, Ritesh; Basu, Sourav; Ghosh, Rajib; Yadav, Dharmendra B.; Surya, Arjun published the artcile< The discovery of potent small molecule activators of human STING>, Name: Ethyl 2-hydroxyacetate, the main research area is human STING activator preparation oxindole benzothiazine quinoline oxazine benzazepine; Cytokines; Immunotherapy; Interferon genes; STING.

The adaptor protein STING plays a major role in innate immune sensing of cytosolic nucleic acids, by triggering a robust interferon response. Despite the importance of this protein as a potential therapeutic target for serious unmet medical conditions including cancer and infectious disease there remains a paucity of STING ligands. Starting with a benzothiazinone series of weak STING activators (human EC50 ∼10μM) we identified several chemotypes with sub-micromolar STING activity across all the major protein polymorphs. An example compound I, based on an oxindole core structure, demonstrated robust on-target functional activation of STING (human EC50 185 nM) in immortalized and primary cells and a cytokine induction fingerprint consistent with STING activation. Our study has identified several related series of potent small mol. human STING activators with potential to be developed as immunomodulatory therapeutics.

European Journal of Medicinal Chemistry published new progress about Homo sapiens. 623-50-7 belongs to class esters-buliding-blocks, and the molecular formula is C4H8O3, Name: Ethyl 2-hydroxyacetate.

Referemce:
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

Qin, Lihong; Mao, Huiwen; Wang, Jianguo; Wang, Yuanyaun; Khan, Salman A.; Zhang, Ying; Qiu, Hong; Jiang, Longwei; He, Lingfeng; Zhang, Yan; Jia, Shaochang published the artcile< A novel polymerase β inhibitor from phage displayed peptide library augments the anti-tumour effects of temozolomide on colorectal cancer>, Category: esters-buliding-blocks, the main research area is temozolomide 10D anticancer polymerasebeta colorectal cancer phage display library; CRC; DNA repair; Inhibitor; Polβ; TMZ.

The therapeutic efficacy of TMZ, a common used drug for chemotherapy, is limited by the resistance from colorectal cancer cells. Base excision repair (BER) pathway has been identified as one of the reasons for drug resistance. By blocking Polβ-dependent BER (Base Excision Repair) pathway, the efficacy of TMZ treatment can be improved greatly. Several Polβ inhibitors that have been identified could not become approved drugs due to lack of potency or specificity. To find therapeutic candidates with exquisite specificity and high affinity to Polβ, phage display technol. was used in the current research. We screened out a candidate Polβ inhibitor, 10 D, that can inhibit the activity of Polβand SP-BER (Short-Patch Base excision Repair) pathway. Co-treatment with 10 D enhanced the sensitivity of colorectal cancer (CRC) cells to TMZ both in vitro and in vivo. Our data suggested that the novel Polβ inhibitor we identified can improve TMZ efficacy and optimize CRC chemotherapy.

Journal of Chemotherapy (Abingdon, United Kingdom) published new progress about Colorectal neoplasm. 112-63-0 belongs to class esters-buliding-blocks, and the molecular formula is C19H34O2, Category: esters-buliding-blocks.

Referemce:
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

Agarwal, Sameer; Sasane, Santosh; Shah, Hardik A.; Pethani, Jignesh P.; Deshmukh, Prashant; Vyas, Vismit; Iyer, Pravin; Bhavsar, Harsh; Viswanathan, Kasinath; Bandyopadhyay, Debdutta; Giri, Poonam; Mahapatra, Jogeswar; Chatterjee, Abhijit; Jain, Mukul R.; Sharma, Rajiv published the artcile< Discovery of N-Cyano-sulfoximineurea Derivatives as Potent and Orally Bioavailable NLRP3 Inflammasome Inhibitors>, Related Products of 112-63-0, the main research area is cyanosulfoximineurea synthesis pharmacokinetics NLRP3 inflammasome IL1beta inflammation.

NLRP3 inflammasome mediated release of interleukin-1β (IL-1β) has been implicated in various diseases. In this study, rationally designed mimics of sulfonylurea moiety were investigated as NLRP3 inhibitors. Our results culminated into discovery of series of unprecedented N-cyano sulfoximineurea derivatives as potent NLRP3 inflammasome inhibitors. Compound 15 (IC50 = 7 nM) and analogs were found to be highly potent and selective NLRP3 inflammasome inhibitor with good pharmacokinetic profile. These effects translate in vivo, as 15, 29, and 34 significantly inhibit NLRP3 dependent IL-1β secretion in mice.

ACS Medicinal Chemistry Letters published new progress about Anti-inflammatory agents. 112-63-0 belongs to class esters-buliding-blocks, and the molecular formula is C19H34O2, Related Products of 112-63-0.

Referemce:
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

Nguyen, Duc Hanh; Perez-Torrente, Jesus J.; Lomba, Laura; Victoria Jimenez, M.; Lahoz, Fernando J.; Oro, Luis A. published the artcile< Unsaturated iridium pyridinedicarboxylate pincer complexes with catalytic activity in borylation of arenes>, Recommanded Product: (9Z,12Z)-Methyl octadeca-9,12-dienoate, the main research area is crystal structure cyclooctenyl iridium pyridinedicarboxylate pincer complex preparation; mol structure cyclooctenyl iridium pyridinedicarboxylate pincer complex; iridium pyridinedicarboxylate pincer complex preparation arene borylation catalyst; cyclooctenyl iridium pyridinedicarboxylate pincer complex preparation pyridine exchange kinetics.

Unsaturated σ,π-cyclooctenyl and hydrido Ir(III) complexes bearing an unusual tridentate dianionic ONO pincer-type ligand have been straightforwardly obtained from 2,6-pyridinedicarboxylic acid and standard Ir(I) starting materials. These complexes efficiently catalyzed the arene C-H borylation under thermal conditions.

Dalton Transactions published new progress about Activation enthalpy. 112-63-0 belongs to class esters-buliding-blocks, and the molecular formula is C19H34O2, Recommanded Product: (9Z,12Z)-Methyl octadeca-9,12-dienoate.

Referemce:
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

Chen, Hao; Li, Chunlin; Hu, Haiyang; Zhang, Bin published the artcile< Activated TRPA1 plays a therapeutic role in TMZ resistance in glioblastoma by altering mitochondrial dynamics>, Recommanded Product: (9Z,12Z)-Methyl octadeca-9,12-dienoate, the main research area is Glioblastoma; Mitochondrial dysfunction; Oxidative stress; TRPA1; Temozolomide.

Abstract: Background: Glioblastoma (GBM) represents nearly one-half of primary brain tumors, and the median survival of patients with GBM is only 14.6 mo. Surgery followed by radiation with concomitant temozolomide (TMZ) therapy is currently the standard of care. However, an increasing body of evidence suggests that GBM acquires resistance to TMZ, compromising the effect of the drug. Thus, further exploration into the mechanism underlying this resistance is urgently needed. Studies have demonstrated that TMZ resistance is associated with DNA damage, followed by altered reactive oxygen species (ROS) production in mitochondria. Studies have also showed that Ca2+-related transient receptor potential (TRP) channels participate in GBM cell proliferation and metastasis, but the detailed mechanism of their involvement remain to be studied. The present study demonstrates the role played by TRPA1 in TMZ resistance in GBM and elucidates the mechanism of resistance. Methods: U251 and SHG-44 cells were analyzed in vitro. A CCK-8 assay was performed to verify the effect of TMZ toxicity on GBM cells. Intracellular ROS levels were detected by DCFH-DA assay. A MitoSOX Red assay was performed to determine the mitochondrial ROS levels. Intracellular Ca2+ levels in the cells were determined with a Fluo-4 AM calcium assay kit. Intracellular GSH levels were determined with GSH and GSSG Assay Kit. MGMT protein, Mitochondrial fission- and fusion-, apoptosis- and motility-related protein expression was detected by western blot assay. A recombinant lentiviral vector was used to infect human U251 cells to overexpress shRNA and generate TRPA1+/+ and neg. control cells. All experiments were repeated. Results: In the U251 and SHG-44 cells, TMZ induced a small increase in the apoptosis rate and intracellular and mitochondrial ROS levels. The expression of antioxidant genes and antioxidants in these cells was also increased by TMZ. However, pretreatment with a TRPA1 agonist significantly decreased the level of antioxidant gene and antioxidants expression and enhanced intracellular and mitochondrial ROS levels. Also TMZ induced the level of MGMT protein increased, and pretreatment with a TRPA1 agonist decreased the MGMT expression. Moreover, Ca2+ influx, mitochondrial damage and cell apoptosis were promoted, and the balance between mitochondrial fission and fusion protein expression was disrupted in these GBM cells. Pretreatment with a TRPA1 inhibitor slightly enhanced the level of antioxidant gene expression and reduced the apoptosis rate. TRPA1 gene overexpression in the U251 cells was similar to that after inhibitor intervention, confirming the aforementioned exptl. results. Conclusion: The present study proved that activating TRPA1 in glioma cells, which leads to mitochondrial damage and dysfunction and ultimately to apoptosis, may decrease the TMZ resistance of GBM cells.

BMC Molecular and Cell Biology published new progress about 112-63-0. 112-63-0 belongs to class esters-buliding-blocks, and the molecular formula is C19H34O2, Recommanded Product: (9Z,12Z)-Methyl octadeca-9,12-dienoate.

Referemce:
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

Li, Xiaoning; Li, Yehui; Wang, Xiang; Wang, Haijun published the artcile< Zirconium-Gallic Acid Coordination Polymer: Catalytic Transfer Hydrogenation of Levulinic Acid and Its Esters into γ-Valerolactone>, Reference of 112-63-0, the main research area is zirconium catalyst preparation surface structure ethyl levulinate hydrogenation.

The conversion of Et levulinate (EL) to produce γ-valerolactone (GVL) through catalytic transfer hydrogenation (CTH) reaction plays a crucial role in the field of biomass catalytic conversion. In this work, a novel Zr-base catalyst with phenate group, phenolic hydroxyl and carboxyl in its structure was prepared by the co-precipitation of natural sources gallic acid and ZrCl4. It was found that Zr-GA has an excellent catalytic performance for this reaction and satisfactory GVL yield could be achieved. Besides, Zr-GA could be easily separated from the reaction system and reused at least six times without a significantly decrease in activity. Meanwhile, various characterizations had proved that Zr-GA is a porous material with acid-base bifunctional sites. The main reason for the high catalytic activity of the Zr-GA was that the synergetic effects of Lewis acid/base sites and Bronsted acid sites and appropriate textural properties. In addition, a possible reaction mechanism was proposed in conjunction with the poisoning experiment and previous reports. The heterogeneous catalyst Zr-GA prepared with gallic acid as a raw material has low cost and recyclability, and has great potential in green chem.

Catalysis Letters published new progress about Crystallinity. 112-63-0 belongs to class esters-buliding-blocks, and the molecular formula is C19H34O2, Reference of 112-63-0.

Referemce:
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

Huertas-Perez, Jose Fernando; Arroyo-Manzanares, Natalia; Hitzler, Dominik; Castro-Guerrero, Francisco German; Gamiz-Gracia, Laura; Garcia-Campana, Ana M. published the artcile< Simple determination of aflatoxins in rice by ultra-high performance liquid chromatography coupled to chemical post-column derivatization and fluorescence detection>, SDS of cas: 112-63-0, the main research area is aflatoxin contamination rice derivatization UHPLC fluorescence; Aflatoxins; Fluorescence detection; Liquid chromatography; Post-column derivatization; Rice.

A fast and simple anal. method was developed and characterized for the determination of aflatoxins (B1, B2, G1 and G2) in rice. The procedure is based on a simple solid-liquid extraction without further clean-up, and anal. by ultra-high performance liquid chromatog. coupled with fluorescence detection. Fluorescence emission of aflatoxins B1 and G1 was enhanced by post-column chem. derivatization using pyridinium bromide perbromide. The anal. method was satisfactorily characterized in white and brown rice. Under optimum conditions, external calibration in solvent could be used for quantification purposes and limits of quantification were below the maximum contents established by the European Union regulation for these contaminants/commodity group combination (0.07-0.14 μg/kg for white rice and 0.20-0.28 μg/kg for brown rice). Recovery studies carried out at three different concentration levels (0.5, 2 and 5 μg/kg) showed values in the range of 84.5-105.3%, and RSDs≤5%.

Food Chemistry published new progress about Extraction. 112-63-0 belongs to class esters-buliding-blocks, and the molecular formula is C19H34O2, SDS of cas: 112-63-0.

Referemce:
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

Kloeckner, Benjamin; Niederer, Kerstin; Fokina, Ana; Frey, Holger; Zentel, Rudolf published the artcile< Conducting Polymer with Orthogonal Catechol and Disulfide Anchor Groups for the Assembly of Inorganic Nanostructures>, Related Products of 71195-85-2, the main research area is conducting orthogonal catechol disulfide anchor assembly inorganic nanostructure; polyoxyalkylene block graft polyvinylcarbazole coating quantum dot cadmium selenide.

To combine several inorganic components with organic material in a controlled special and permanent manner still remains a difficult issue. Two specifically functionalized block copolymers were synthesized sep. and combined in a second step. A heterofunctional poly(ethylene glycol) (PEG) block copolymer bearing a single amino unit, a short PEG spacer, and multiple catechol functionalities was obtained via anionic ring-opening polymerization (AROP). Using the reversible addition-fragmentation chain transfer (RAFT) radical polymerization technique, a semiconducting block copolymer with carbazole side groups was obtained. The second polyacrylate block contained reactive ester groups and was polymerized onto this hole conducting block. By substitution of the reactive esters with the amino functional PEG-catechol block copolymer and cysteamine Me disulfide, a hole conducting polymer material with two orthogonal anchor groups for the coating of CdSe QDs, and also for TiO2, was obtained. TEM images show that upon coating of both materials we were able to obtain QDs homogeneously distributed at the surface of TiO2 nanoparticles. This spatial assembly is a consequence of the special directing features of the copolymer, possessing two orthogonal anchor groups combined in one material.

Macromolecules (Washington, DC, United States) published new progress about Aggregates. 71195-85-2 belongs to class esters-buliding-blocks, and the molecular formula is C9H3F5O2, Related Products of 71195-85-2.

Referemce:
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

Khan, Masarrat Majid; Sangshetti, Jaiprakash; Khan, Zeeshan; Shaikh, Asra Mumtaaz published the artcile< Application of QbD in method development of stavudine>, Application In Synthesis of 112-63-0, the main research area is stavudine antiviral agent high performance liquid chromatog.

The HPLC method for Stavudine has been developed using a quality by design concept. In the recent times due to regulatory requirement QbD (Quality by Design) has gained more importance. Chromatog. study has been achieved on a C18 column (3.9 x 300, 10μ particle size). The mobile phase consists of buffer (mono potassium phosphate): methanol (70:30). The factors like flow rate, injection volume and wavelength was found to be critical to maintain in method development of HPLC. Hence Box-Behnken optimization model was applied for the main, interaction and quadratic effects of these three factors has been studied on the selected response. Effects of these parameters were also studied on tailing factor (resolution). Results were analyzed using surface diagram. The Verification of the software generated result has been carried by using six replicates of the run. Lastly validation of the developed method was carried out by applying guidelines and parameters give by ICH (ICH Guidelines).

World Journal of Pharmaceutical Research published new progress about Antiviral agents. 112-63-0 belongs to class esters-buliding-blocks, and the molecular formula is C19H34O2, Application In Synthesis of 112-63-0.

Referemce:
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

Manjunatha, Ujjini H.; Vinayak, Sumiti; Zambriski, Jennifer A.; Chao, Alexander T.; Sy, Tracy; Noble, Christian G.; Bonamy, Ghislain M. C.; Kondreddi, Ravinder R.; Zou, Bin; Gedeck, Peter; Brooks, Carrie F.; Herbert, Gillian T.; Sateriale, Adam; Tandel, Jayesh; Noh, Susan; Lakshminarayana, Suresh B.; Lim, Siau H.; Goodman, Laura B.; Bodenreider, Christophe; Feng, Gu; Zhang, Lijun; Blasco, Francesca; Wagner, Juergen; Leong, F. Joel; Striepen, Boris; Diagana, Thierry T. published the artcile< A Cryptosporidium PI(4)K inhibitor is a drug candidate for cryptosporidiosis>, Safety of (9Z,12Z)-Methyl octadeca-9,12-dienoate, the main research area is Cryptosporidium phosphatidylinositol kinase inhibitor preparation cryptosporidiosis diarrhea.

Diarrhoeal disease is responsible for 8.6% of global child mortality. Recent epidemiol. studies found the protozoan parasite Cryptosporidium to be a leading cause of paediatric diarrhoea, with particularly grave impact on infants and immunocompromised individuals. There is neither a vaccine nor an effective treatment. Here we establish a drug discovery process built on scalable phenotypic assays and mouse models that take advantage of transgenic parasites. Screening a library of compounds with anti-parasitic activity, we identify pyrazolopyridines as inhibitors of Cryptosporidium parvum and Cryptosporidium hominis. Oral treatment with the pyrazolopyridine KDU731 results in a potent reduction in intestinal infection of immunocompromised mice. Treatment also leads to rapid resolution of diarrhoea and dehydration in neonatal calves, a clin. model of cryptosporidiosis that closely resembles human infection. Our results suggest that the Cryptosporidium lipid kinase PI(4)K (phosphatidylinositol-4-OH kinase) is a target for pyrazolopyridines and that KDU731 warrants further preclin. evaluation as a drug candidate for the treatment of cryptosporidiosis.

Nature (London, United Kingdom) published new progress about Antidiarrheals. 112-63-0 belongs to class esters-buliding-blocks, and the molecular formula is C19H34O2, Safety of (9Z,12Z)-Methyl octadeca-9,12-dienoate.

Referemce:
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics