Tag: M.W=450-500

Christensen, Matthew D. published the artcileAn inhibitor screen identifies histone-modifying enzymes as mediators of polymer-mediated transgene expression from plasmid DNA, Formula: C25H34N4O2S, the publication is Journal of Controlled Release (2018), 210-223, database is CAplus and MEDLINE.

Effective transgene expression in mammalian cells relies on successful delivery, cytoplasmic trafficking, and nuclear translocation of the delivered vector, but delivery is impeded by several formidable physicochem. barriers on the surface of and within the target cell. Although methods to overcome cellular exclu. and endosomal entrap. have been studied extensively, strategies to overcome ineffi. nuclear entry and subseq. intranuclear barriers to effec. transient gene expre. have only been sparsely explored. In particular, the role of nuclear packaging of DNA with histone proteins. In this work, a parallel screen of small mol. inhibitors of chromatin-modifying enzy. resulted in the identifi. of class I/II HDACs, sirtuins, LSD1, HATs, and the methyltransferases EZH2 and MLL as targets whose inhibi. led to the enhanc. of transgene expre. following polymer-mediated delivery of plasmid DNA. Quant. PCR studies revealed that HDAC inhibi. enhances the amount of plasmid DNA delivered to the nucleus in UMUC3 human bladder cancer cells. N-ChIP-qPCR experiments in CHO-K1 cells indicated that plasmids indeed interact with intracellular core Histone H3, and inhibitors of HDAC and LSD1 proteins. Pair-wise treatments of effective inhibitors led to synergistic enhanc. of transgene expression to varying extents in both cell types. Our results demonstrate that the ability to modulate enzy. that play a role in epigenetic processes can enhance the efficacy of non-viral gene delivery.

Journal of Controlled Release published new progress about 1011557-82-6. 1011557-82-6 belongs to amides-buliding-blocks, auxiliary class Epigenetics,Sirtuin, name is 4-(tert-Butyl)-N-((4-(5-(dimethylamino)pentanamido)phenyl)carbamothioyl)benzamide, and the molecular formula is C25H34N4O2S, Formula: C25H34N4O2S.

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

Xu-Xu, Qing-Feng published the artcileSynthesis of Benzoisoselenazolones via Rh(III)-Catalyzed Direct Annulative Selenation by Using Elemental Selenium, Recommanded Product: (3R,4R,5S,6R)-6-(Acetoxymethyl)-3-benzamidotetrahydro-2H-pyran-2,4,5-triyl triacetate, the publication is Chemistry – A European Journal (2021), 27(71), 17952-17959, database is CAplus and MEDLINE.

In this manuscript, a rhodium-catalyzed direct selenium annulation by using stable and tractable elemental selenium was introduced. A series of benzamides as well as acrylamides RNHC(O)R¹ (R = Me, cyclohexyl, Bn, etc.; R¹ = prop-1-en-2-yl, Ph, thiophen-2-yl, etc.) were successfully coupled with selenium under mild reaction conditions, and the obtained isoselenazolones I (R² = H, Me, Ph, Cl; R³ = H, Me, OMe, Cl; R⁴ = H, OMe, Br, F; R⁵ = H, Me, OMe, Cl) and II (R⁶ = Me, Ph; R⁷ = H; R⁶R⁷ = -SCH=CH-) could be pivotal synthetic precursors for several organoselenium compounds e.g., III. Based on the designed control experiments and X-ray absorption spectroscopy measurements, an unprecedented selenation mechanism involving a highly electrophilic Se(IV) species as the reactive selenium donor was proposed. The reaction mechanism was further verified by a computational study.

Chemistry – A European Journal published new progress about 14086-92-1. 14086-92-1 belongs to amides-buliding-blocks, auxiliary class Sugar Units,Glu, name is (3R,4R,5S,6R)-6-(Acetoxymethyl)-3-benzamidotetrahydro-2H-pyran-2,4,5-triyl triacetate, and the molecular formula is C9H13NO2, Recommanded Product: (3R,4R,5S,6R)-6-(Acetoxymethyl)-3-benzamidotetrahydro-2H-pyran-2,4,5-triyl triacetate.

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

Birdsall, Robert E. published the artcileA sensitive multidimensional method for the detection, characterization, and quantification of trace free drug species in antibody-drug conjugate samples using mass spectral detection, Recommanded Product: (S)-2-((S)-2-(6-(2,5-Dioxo-2,5-dihydro-1H-pyrrol-1-yl)hexanamido)-3-methylbutanamido)-5-ureidopentanoic acid, the publication is mAbs (2016), 8(2), 306-317, database is CAplus and MEDLINE.

Conjugation processes and stability studies associated with the production and shelf life of antibody-drug conjugates (ADCs) can result in free (non-conjugated) drug species. These free drug species can increase the risk to patients and reduce the efficacy of the ADC. Despite stringent purification steps, trace levels of free drug species may be present in formulated ADCs, reducing the therapeutic window. The reduction of sample preparation steps through the incorporation of multidimensional techniques has afforded analysts more efficient methods to assess trace drug species. Multidimensional methods coupling size-exclusion and reversed phase liquid chromatog. with ultra-violet detection (SEC-RPLC/UV) have been reported, but offer limited sensitivity and can limit method optimization. The current study addresses these challenges with a multidimensional method that is specific, sensitive, and enables method control in both dimensions via coupling of an online solid phase extraction column to RPLC with mass spectral detection (SPE-RPLC/MS). The proposed method was evaluated using an antibody-fluorophore conjugate (AFC) as an ADC surrogate to brentuximab vedotin and its associated parent maleimide-val-cit-DSEA payload and the derived N-acetylcysteine adduct formed during the conjugation process. Assay sensitivity was found to be 2 orders more sensitive using MS detection in comparison to UV-based detection with a nominal limit of quantitation of 0.30 ng/mL (1.5 pg on-column). Free-drug species were present in an unadulterated ADC surrogate sample at concentrations below 7 ng/mL, levels not detectable by UV alone. The proposed SPE-RPLC/MS method provides a high degree of specificity and sensitivity in the assessment of trace free drug species and offers improved control over each dimension, enabling straightforward integration into existing or novel workflows.

mAbs published new progress about 916746-27-5. 916746-27-5 belongs to amides-buliding-blocks, auxiliary class ADC Linker,Enzymatic Cleavage Linker, name is (S)-2-((S)-2-(6-(2,5-Dioxo-2,5-dihydro-1H-pyrrol-1-yl)hexanamido)-3-methylbutanamido)-5-ureidopentanoic acid, and the molecular formula is C21H33N5O7, Recommanded Product: (S)-2-((S)-2-(6-(2,5-Dioxo-2,5-dihydro-1H-pyrrol-1-yl)hexanamido)-3-methylbutanamido)-5-ureidopentanoic acid.

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

Pirrie, Lisa published the artcileDiscovery and validation of SIRT2 inhibitors based on tenovin-6: use of a ¹H-NMR method to assess deacetylase activity, Recommanded Product: 4-(tert-Butyl)-N-((4-(5-(dimethylamino)pentanamido)phenyl)carbamothioyl)benzamide, the publication is Molecules (2012), 12206-12224, database is CAplus and MEDLINE.

The search for potent and selective sirtuin inhibitors continues as chem. tools of this type are of use in helping to assign the function of this interesting class of deacetylases. Here we describe SAR studies starting from the unselective sirtuin inhibitor tenovin-6. These studies identify a sub-micromolar inhibitor that has increased selectivity for SIRT2 over SIRT1 compared to tenovin-6. In addition, a ¹H-NMR-based method is developed and used to validate further this class of sirtuin inhibitors. A thermal shift anal. of SIRT2 in the presence of tenovin-6, -43, a control tenovin and the known SIRT2 inhibitor AGK2 is also presented.

Molecules published new progress about 1011557-82-6. 1011557-82-6 belongs to amides-buliding-blocks, auxiliary class Epigenetics,Sirtuin, name is 4-(tert-Butyl)-N-((4-(5-(dimethylamino)pentanamido)phenyl)carbamothioyl)benzamide, and the molecular formula is C25H34N4O2S, Recommanded Product: 4-(tert-Butyl)-N-((4-(5-(dimethylamino)pentanamido)phenyl)carbamothioyl)benzamide.

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

Marshall, Glenn M. published the artcileSIRT1 promotes N-Myc oncogenesis through a positive feedback loop involving the effects of MKP3 and ERK on N-Myc protein stability, Safety of 4-(tert-Butyl)-N-((4-(5-(dimethylamino)pentanamido)phenyl)carbamothioyl)benzamide, the publication is PLoS Genetics (2011), 7(6), e1002135, database is CAplus and MEDLINE.

The N-Myc oncoprotein is a critical factor in neuroblastoma tumorigenesis which requires addnl. mechanisms converting a low-level to a high-level N-Myc expression. N-Myc protein is stabilized when phosphorylated at Serine 62 by phosphorylated ERK protein. Here we describe a novel pos. feedback loop whereby N-Myc directly induced the transcription of the class III histone deacetylase SIRT1, which in turn increased N-Myc protein stability. SIRT1 binds to Myc Box I domain of N-Myc protein to form a novel transcriptional repressor complex at gene promoter of mitogen-activated protein kinase phosphatase 3 (MKP3), leading to transcriptional repression of MKP3, ERK protein phosphorylation, N-Myc protein phosphorylation at Serine 62, and N-Myc protein stabilization. Importantly, SIRT1 was up-regulated, MKP3 down-regulated, in pre-cancerous cells, and preventative treatment with the SIRT1 inhibitor Cambinol reduced tumorigenesis in TH-MYCN transgenic mice. Our data demonstrate the important roles of SIRT1 in N-Myc oncogenesis and SIRT1 inhibitors in the prevention and therapy of N-Myc-induced neuroblastoma.

PLoS Genetics published new progress about 1011557-82-6. 1011557-82-6 belongs to amides-buliding-blocks, auxiliary class Epigenetics,Sirtuin, name is 4-(tert-Butyl)-N-((4-(5-(dimethylamino)pentanamido)phenyl)carbamothioyl)benzamide, and the molecular formula is C25H34N4O2S, Safety of 4-(tert-Butyl)-N-((4-(5-(dimethylamino)pentanamido)phenyl)carbamothioyl)benzamide.

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

Sun, Jiangtao published the artcileTargeting histone deacetylase SIRT1 selectively eradicates EGFR TKI-resistant cancer stem cells via regulation of mitochondrial oxidative phosphorylation in lung adenocarcinoma, SDS of cas: 1011557-82-6, the publication is Neoplasia (New York, NY, United States) (2020), 22(1), 33-46, database is CAplus and MEDLINE.

Lung adenocarcinoma (LAD) is a human malignancy successfully treated with the tyrosine kinase inhibitor (TKI) gefitinib; however, the enrichment of therapy resistant cancer stem cells (CSCs) in such patients is assumed to be a source of treatment failure. Evaluation of LAD cell populations treated with the TKI inhibitor gefitinib identified unique aspects of a subpopulation of tumor cells exhibiting stem-like properties and mitochondria-specific metabolic features along with their reliance on sirtuin 1 (SIRT1) for survival advantage. Accordingly, loss of the phenotype present in resistant CSC clones either by targeting the energy metabolism with tigecycline or tenovin-6 inhibited their dependency on mtOXPHOS and sensitized them for a more pronounced and long-lasting TKI therapeutic effect. The results specifically demonstrated that combined therapy with TV-6 and gefitinib resulted in tumor regression in xenograft mouse models, whereas administration of a single agent showed no such efficacy. Importantly, combined treatment with TV-6 also decreased the ED of gefitinib necessary for treatment response. Clin. anal. demonstrated that high-profile SIRT1 and mtOXPHOS proteins were associated with recurrence and poor prognosis in LAD patients. These observations support the CSC hypothesis for cancer relapse and advocate use of mitochondria-targeting inhibitors as part of combinatorial therapy in a variety of clin. settings, as well as for reducing TKI dosage in LAD patients.

Neoplasia (New York, NY, United States) published new progress about 1011557-82-6. 1011557-82-6 belongs to amides-buliding-blocks, auxiliary class Epigenetics,Sirtuin, name is 4-(tert-Butyl)-N-((4-(5-(dimethylamino)pentanamido)phenyl)carbamothioyl)benzamide, and the molecular formula is C5H9IO2, SDS of cas: 1011557-82-6.

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

Sproviero, Jorge F. published the artcileAmmonolysis of acylated 2-amino-2-deoxy-D-glucoses, Name: (3R,4R,5S,6R)-6-(Acetoxymethyl)-3-benzamidotetrahydro-2H-pyran-2,4,5-triyl triacetate, the publication is Anales de la Asociacion Quimica Argentina (1965), 53(3-4), 261-7, database is CAplus.

MeOH-NH3 or MeONa treatment of tetra-O-acetyl-N-acetyl-D-glucosamine nitrile gave no pentose derivatives N-Acetyl-and N-benzoyl-D-glucosamines were stable to MeOH-NH3, but acetylated and benzoylated derivatives gave low recoveries and appreciable quantities of chromogens [including 2-(1,2-dihydroxyethyl)-4-acetamidofuran] and reducing substances, identified on paper chromatog.

Anales de la Asociacion Quimica Argentina published new progress about 14086-92-1. 14086-92-1 belongs to amides-buliding-blocks, auxiliary class Sugar Units,Glu, name is (3R,4R,5S,6R)-6-(Acetoxymethyl)-3-benzamidotetrahydro-2H-pyran-2,4,5-triyl triacetate, and the molecular formula is C4H10O2, Name: (3R,4R,5S,6R)-6-(Acetoxymethyl)-3-benzamidotetrahydro-2H-pyran-2,4,5-triyl triacetate.

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

Wu, Huaiguo published the artcilemiR-34a in extracellular vesicles from bone marrow mesenchymal stem cells reduces rheumatoid arthritis inflammation via the cyclin I/ATM/ATR/p53 axis, Name: 4-(tert-Butyl)-N-((4-(5-(dimethylamino)pentanamido)phenyl)carbamothioyl)benzamide, the publication is Journal of Cellular and Molecular Medicine (2021), 25(4), 1896-1910, database is CAplus and MEDLINE.

Extracellular vesicles (Evs) participate in the development of rheumatoid arthritis (RA), but the mechanisms remain unclear. This study aimed to determine the mechanism by which microRNA-34a (miR-34a) contained in bone marrow mesenchymal stem cell (BM-MSC)-derived Evs functions in RA fibroblast-like synoviocytes (RA-FLSs). BM-MSC-derived Evs and an Evs inhibitor were extracted A rat model of RA was established. miR-34a gain- and loss-of-function experiments were performed, and the inflammation in rat synovial fluid and tissues was detected. The role of miR-34a in RA-FLSs was also measured in vitro. The target gene of miR-34a was predicted using the online software TargetScan and identified using a dual-luciferase reporter gene assay, and the activation of the ATM/ATR/p53 signalling pathway was assessed. BM-MSC-derived Evs mainly elevated miR-34a expression, which reduced RA inflammation in vivo and inhibited RA-FLS proliferation and resistance to apoptosis in vitro, while inhibited miR-34a expression enhanced RA development. In addition, miR-34a could target cyclin I to activate the ATM/ATR/p53 signalling pathway, thus inhibiting abnormal RA-FLS growth and RA inflammation. Our study showed that miR-34a contained in BM-MSC-derived Evs could reduce RA inflammation by inhibiting the cyclin I/ATM/ATR/p53 signalling pathway.

Journal of Cellular and Molecular Medicine published new progress about 1011557-82-6. 1011557-82-6 belongs to amides-buliding-blocks, auxiliary class Epigenetics,Sirtuin, name is 4-(tert-Butyl)-N-((4-(5-(dimethylamino)pentanamido)phenyl)carbamothioyl)benzamide, and the molecular formula is C19H24BNO2, Name: 4-(tert-Butyl)-N-((4-(5-(dimethylamino)pentanamido)phenyl)carbamothioyl)benzamide.

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

Dai, Wei published the artcileClass III-specific HDAC inhibitor Tenovin-6 induces apoptosis, suppresses migration and eliminates cancer stem cells in uveal melanoma, Application In Synthesis of 1011557-82-6, the publication is Scientific Reports (2016), 22622, database is CAplus and MEDLINE.

Uveal melanoma (UM) is the most common intraocular malignancy in adults. Despite improvements in surgical, radiation and chemotherapy treatments, the overall survival of UM and prognosis remain poor. In the present study, we hypothesized that Sirtuin 1 and 2 (SIRT1/2), class III histone deacetylases (HDACs), were critical in controlling the destiny of bulk tumor cells and cancer stem cells (CSCs) of UM. We testified this hypothesis in four lines of UM cells (92.1, Mel 270, Omm 1 and Omm 2.3). Our results showed that inhibition of SIRT1/2 by Tenovin-6 induced apoptosis in UM cells by activating the expression of tumor suppressor genes such as p53 and elevating reactive oxygen species (ROS). Tenovin-6 inhibited the growth of UM cells. Tenovin-6 and vinblastine was synergistic in inducing apoptosis of UM cell line 92.1 and Mel 270. Furthermore, Tenovin-6 eliminated cancer stem cells in 92.1 and Mel 270 cells. In conclusion, our findings suggest that Tenovin-6 may be a promising agent to kill UM bulk tumor cells and CSCs.

Scientific Reports published new progress about 1011557-82-6. 1011557-82-6 belongs to amides-buliding-blocks, auxiliary class Epigenetics,Sirtuin, name is 4-(tert-Butyl)-N-((4-(5-(dimethylamino)pentanamido)phenyl)carbamothioyl)benzamide, and the molecular formula is C25H34N4O2S, Application In Synthesis of 1011557-82-6.

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

Pan, Li-Qiang published the artcileHetero-modification of TRAIL trimer for improved drug delivery and in vivo antitumor activities, HPLC of Formula: 916746-27-5, the publication is Scientific Reports (2015), 14872, database is CAplus and MEDLINE.

Poor pharmacokinetics and resistance within some tumor cell lines have been the major obstacles during the preclin. or clin. application of TRAIL (tumor-necrosis-factor (TNF)-related apoptosis-inducing ligand). The half-life of TRAIL_114-281 (114 to 281 amino acids) was revealed to be no more than 30 min across species. Therefore maleimido activated PEG (polyethylene glycol) and MMAE (Monomethyl Auristatin E) were applied to site-specifically conjugate with the mutated cysteines from different monomers of TRAIL successively, taking advantage of steric effects involved within TRAIL mutant conjugations. As a result, TRAIL trimer was hetero-modified for different purposes. And the resulting PEG-TRAIL-vcMMAE conjugate exhibited dramatically improved half-life (11.54 h), favorable in vivo targeting capability and antitumor activities while no sign of toxicity in xenograft models, suggesting it’s a viable therapeutic and drug delivery strategy.

Scientific Reports published new progress about 916746-27-5. 916746-27-5 belongs to amides-buliding-blocks, auxiliary class ADC Linker,Enzymatic Cleavage Linker, name is (S)-2-((S)-2-(6-(2,5-Dioxo-2,5-dihydro-1H-pyrrol-1-yl)hexanamido)-3-methylbutanamido)-5-ureidopentanoic acid, and the molecular formula is C21H33N5O7, HPLC of Formula: 916746-27-5.

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