Month: December 2022

Fang, Huafeng published the artcileCationic Shell-Cross-Linked Knedel-like (cSCK) Nanoparticles for Highly Efficient PNA Delivery, Product Details of C40H35N7O8, the publication is Molecular Pharmaceutics (2009), 6(2), 615-626, database is CAplus and MEDLINE.

Peptide nucleic acids have a number of features that make them an ideal platform for the development of in vitro biol. probes and tools. Unfortunately, their inability to pass through membranes has limited their in vivo application as diagnostic and therapeutic agents. Herein, we describe the development of cationic shell-crosslinked knedel-like (cSCK) nanoparticles as highly efficient vehicles for the delivery of PNAs into cells, either through electrostatic complexation with a PNA·ODN hybrid, or through a bioreductively cleavable disulfide linkage to a PNA. These delivery systems are better than the standard Lipofectamine/ODN-mediated method and much better than the Arg₉-mediated method for PNA delivery in HeLa cells, showing lower toxicity and higher bioactivity. The cSCKs were also found to facilitate both endocytosis and endosomal release of the PNAs, while themselves remaining trapped in the endosomes.

Molecular Pharmaceutics published new progress about 186046-83-3. 186046-83-3 belongs to amides-buliding-blocks, auxiliary class Purine,Carboxylic acid,Amine,Benzene,Amide,Others,PNA,, name is 2-(N-(2-((((9H-Fluoren-9-yl)methoxy)carbonyl)amino)ethyl)-2-(2-(((benzhydryloxy)carbonyl)amino)-6-oxo-5H-purin-9(6H)-yl)acetamido)acetic acid, and the molecular formula is C40H35N7O8, Product Details of C40H35N7O8.

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

Amirkhanov, Nariman V. published the artcileImaging Human Pancreatic Cancer Xenografts by Targeting Mutant KRAS2 mRNA with [111In]DOTAn-Poly(diamidopropanoyl)m-KRAS2 PNA-d(Cys-Ser-Lys-Cys) Nanoparticles, Recommanded Product: 2-(N-(2-((((9H-Fluoren-9-yl)methoxy)carbonyl)amino)ethyl)-2-(2-(((benzhydryloxy)carbonyl)amino)-6-oxo-5H-purin-9(6H)-yl)acetamido)acetic acid, the publication is Bioconjugate Chemistry (2010), 21(4), 731-740, database is CAplus and MEDLINE.

95% Of patients with ductal pancreatic cancer carry 12th codon activating mutations in their KRAS2 oncogenes. Early whole body imaging of mutant KRAS2 mRNA activation in pancreatic cancer would contribute to disease management. Scintigraphic hybridization probes to visualize gene activity in vivo constitute a new paradigm in mol. imaging. We have previously imaged mutant KRAS2 mRNA activation in pancreatic cancer xenografts by positron emission tomog. (PET) based on a single radiometal, ⁶⁴Cu, chelated to a 1,4,7,10-tetra(carboxymethylaza)cyclododecane (DOTA) chelator, connected via a flexible, hydrophilic spacer, aminoethoxyethoxyacetate (AEEA), to the N-terminus of a mutant KRAS2 peptide nucleic acid (PNA) hybridization probe. A peptide analog of insulin-like growth factor 1 (IGF1), connected to a C-terminal AEEA, enabled receptor-mediated endocytosis. We hypothesized that a polydiamidopropanoyl (PDAP) dendrimer (generation m), with increasing numbers (n) of DOTA chelators, extended via an N-terminal AEEA from a mutant KRAS2 PNA with a C-terminal AEEA and IGF1 analog could enable more intense external imaging of pancreatic cancer xenografts that overexpress IGF1 receptor and mutant KRAS2 mRNA. ([¹¹¹In]DOTA-AEEA)_n-PDAP^m-AEEA₂-KRAS2 PNA-AEEA-IGF1 analogs were prepared and administered i.v. into immunocompromised mice bearing human AsPC1 (G12D) pancreatic cancer xenografts. CAPAN2 (G12 V) pancreatic cancer xenografts served as a cellular KRAS2 mismatch control. Scintigraphic tumor/muscle image intensity ratios for complementary [¹¹¹In]_n-PDAP^m-KRAS2 G12D probes increased from 3.1 ± 0.2 at n = 2, m = 1, to 4.1 ± 0.3 at n = 8, m = 3, to 6.2 ± 0.4 at n = 16, m = 4, in AsPC1 (G12D) xenografts. Single mismatch [¹¹¹In]_n-PDAP^m-KRAS2 G12 V control probes showed lower tumor/muscle ratios (3.0 ± 0.6 at n = 2, m = 1, 2.6 ± 0.9 at n = 8, m = 3, and 3.7 ± 0.3 at n = 16, m = 4). The mismatch results were comparable to the PNA-free [¹¹¹In]DOTA control results. Simultaneous administration of nonradioactive Gd_n-KRAS2 G12 V probes (n = 2 or 8) increased accumulation of [¹¹¹In]₈KRAS2 G12 V probes 3-6-fold in pancreatic cancer CAPAN2 xenografts and other tissues, except for a 2-fold decrease in the kidneys. As a result, tissue distribution tumor/muscle ratios of ¹¹¹In uptake increased from 3.1 ± 0.5 to 6.5 ± 1.0, and the kidney/tumor ratio of ¹¹¹In uptake decreased by more than 5-fold from 174.8 ± 17.5 to 30.8 ± 3.1. Thus, PDAP dendrimers with up to 16 DOTA chelators attached to PNA-IGF1 analogs, as well as simultaneous administration of the elevated dose of nonradioactive Gd_n-KRAS2 G12 V probes, enhanced tumor uptake of [¹¹¹In]_nKRAS2 PNA probes. These results also imply that Gd(III) dendrimeric hybridization probes might be suitable for magnetic resonance imaging of gene expression in tumors, because the higher generations of the dendrimers, including the NMR contrast Gd_n-KRAS2 G12 V probes, improved tumor accumulation of the probes and specificity of tumor imaging.

Bioconjugate Chemistry published new progress about 186046-83-3. 186046-83-3 belongs to amides-buliding-blocks, auxiliary class Purine,Carboxylic acid,Amine,Benzene,Amide,Others,PNA,, name is 2-(N-(2-((((9H-Fluoren-9-yl)methoxy)carbonyl)amino)ethyl)-2-(2-(((benzhydryloxy)carbonyl)amino)-6-oxo-5H-purin-9(6H)-yl)acetamido)acetic acid, and the molecular formula is C40H35N7O8, Recommanded Product: 2-(N-(2-((((9H-Fluoren-9-yl)methoxy)carbonyl)amino)ethyl)-2-(2-(((benzhydryloxy)carbonyl)amino)-6-oxo-5H-purin-9(6H)-yl)acetamido)acetic acid.

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

Zeng, Hongyun published the artcileMethod for synthesis of 2,5-diaryl substituted thiazoles, Recommanded Product: 3-Methoxybenzothioamide, the publication is Youji Huaxue (2020), 40(8), 2535-2542, database is CAplus.

Thiazole ring is an important five-membered aromatic heterocyclic ring, and its derivatives have various biol. activities and are widely used in medicine. The synthesis of 2,5-diarylthiazole derivatives by acylation, thiolation, cyclization and Heck reaction using inexpensive and readily available substituted benzoic acid as raw materials was developed. The key point was to optimize the Heck reaction conditions and explore the possible reaction mechanism. The method has mild reaction conditions, simple operation, and good substrate universality, which provides a new direction for the synthesis of 2,5-diaryl substituted thiazoles.

Youji Huaxue published new progress about 64559-06-4. 64559-06-4 belongs to amides-buliding-blocks, auxiliary class Amine,Benzene,Amide,Ether, name is 3-Methoxybenzothioamide, and the molecular formula is C6H12N2O, Recommanded Product: 3-Methoxybenzothioamide.

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

Wei, Jie published the artcileThe COX-2-PGE2 pathway promotes tumor evasion in colorectal adenomas, Quality Control of 169590-42-5, the publication is Cancer Prevention Research (2022), 15(5), 285-296, database is CAplus and MEDLINE.

The mechanisms underlying the regulation of a checkpoint receptor, PD-1, in tumor-infiltrating immune cells during the development of colorectal cancer are not fully understood. Here we demonstrate that COX-2-derived PGE2, an inflammatory mediator and tumor promoter, induces PD-1 expression by enhancing NFκB’s binding to the PD-1 promoter via an EP4-PI3K-Akt signaling pathway in both CD8+ T cells and macrophages. Moreover, PGE2 suppresses CD8+ T-cell proliferation and cytotoxicity against tumor cells and impairs macrophage phagocytosis of cancer cells via an EP4-PI3K-Akt-NFκB-PD-1 signaling pathway. In contrast, inhibiting the COX-2-PGE2-EP4 pathway increases intestinal CD8+ T-cell activation and proliferation and enhances intestinal macrophage phagocytosis of carcinoma cells accompanied by reduction of PD-1 expression in intestinal CD8+ T cells and macrophages in ApcMin/+ mice. PD-1 expression correlates well with COX-2 levels in human colorectal cancer specimens. Both elevated PD-1 and COX-2 are associated with poorer overall survival in patients with colorectal cancer. Our results uncover a novel role of PGE2 in tumor immune evasion. They may provide the rationale for developing new therapeutic approaches to subvert this process by targeting immune checkpoint pathways using EP4 antagonists. In addition, our findings reveal a novel mechanism explaining how NSAIDs reduce colorectal cancer risk by suppressing tumor immune evasion.

Cancer Prevention Research published new progress about 169590-42-5. 169590-42-5 belongs to amides-buliding-blocks, auxiliary class Sulfamide,Immunology/Inflammation,COX, name is 4-(5-(p-Tolyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)benzenesulfonamide, and the molecular formula is C28H29NO4, Quality Control of 169590-42-5.

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

Liu, Zhendong published the artcileThe regulating effect of Tibet Opuntia ficus-indica (Linn.) Mill. polysaccharides on the intestinal flora of cyclophosphamide-induced immunocompromised mice, Product Details of C17H14F3N3O2S, the publication is International Journal of Biological Macromolecules (2022), 570-579, database is CAplus and MEDLINE.

The stem of Opuntia species, a traditional medicinal plant, is widely used as food and functional raw material because of its rich polysaccharide content. There have been many studies on the immune function of polysaccharides from Opuntia stem, but only few have examined this function with respect to intestinal microbes. In this study, the effects of different concentrations of Opuntia stem polysaccharides on the immunity and intestinal microflora of cyclophosphamide (CTX)-induced immunocompromised mice were explored. The results showed that Tibet Opuntia ficus-indica (Linn.) Mill. polysaccharides (ODPs) could effectively increase the white blood cells (WBC) count index of mice and improve their thymus and spleen indexes, while effectively promoting the secretion of IL-4, IL-1β, TNF-α and IFN-γ, with these effects being dependent on the concentration of crude polysaccharides. The intake of ODPs significantly regulated the relative abundance of Lactobacillus, Bacteroides and Akkermansia, and the new dominant intestinal bacterial species were Deferribacteres, Actinomycetes, Firmicutes, Tenericutes, Actinomycetes and Pasteurella. In addition, the ODPs could effectively enhance the metabolic level of lysine synthesis and decomposition, regulate the gene expression level after immune disorders, and enhance the overall health of the immunodeficient mice.

International Journal of Biological Macromolecules published new progress about 169590-42-5. 169590-42-5 belongs to amides-buliding-blocks, auxiliary class Sulfamide,Immunology/Inflammation,COX, name is 4-(5-(p-Tolyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)benzenesulfonamide, and the molecular formula is C17H14F3N3O2S, Product Details of C17H14F3N3O2S.

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

Jin, Guohua published the artcileCelecoxib Reverse Invasion and Metastasis of Gastric Cancer through Lnc_AC006548.28-miR-223-LAMC2 Pathway., Quality Control of 169590-42-5, the publication is Computational intelligence and neuroscience (2022), 6140727, database is MEDLINE.

Celecoxib, a specific cyclooxygenase-2 (COX-2) inhibitor, is a traditional nonsteroidal antipyretic analgesic and anti-inflammatory drug commonly used in clinic, which has inhibitory effect on colorectal cancer, gastric cancer, and other malignant tumors. This study showed that Celecoxib could significantly reverse the invasion and metastasis of gastric cancer and improved the pathological changes due to GC. We collected the clinical specimens to analyze the correlation between the expression of Lnc_AC006548.28, miR-223, and LAMC2. In the mouse model, Celecoxib can slowdown the growth of GC tumor and the occurrence of this effect may depend on Lnc_AC006548.28-miR-223-LAMC2 pathway, in vitro transfection, RT-PCR, western blot, CCK8, small chamber assay, flow cytometry, and immunohistochemistry to retest the protective effect of celecoxib. Our results showed that Celecoxib could reverse invasion and metastasis of gastric cancer through Lnc_AC006548.28-miR-223-LAMC2 pathway.

Computational intelligence and neuroscience published new progress about 169590-42-5. 169590-42-5 belongs to amides-buliding-blocks, auxiliary class Sulfamide,Immunology/Inflammation,COX, name is 4-(5-(p-Tolyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)benzenesulfonamide, and the molecular formula is C17H14F3N3O2S, Quality Control of 169590-42-5.

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

Bonaga, Llorente V. R. published the artcileCobalt-mediated cyclotrimerization of bis-alkynes and cyanamides, Application of N,N-Dibenzylcyanamide, the publication is Chemical Communications (Cambridge, United Kingdom) (2004), 2394-2395, database is CAplus and MEDLINE.

CpCo(CO)₂-mediated cyclotrimerization of bis-alkynes and cyanamides provides multi-substituted (amino)pyridines, including macrocyclic products, in 50% yield. For example, the dicarbonyl(η⁵-cyclopentadienyl)cobaltate(1-)-catalyzed cyclotrimerization of di(2-propynyl)propanedioic acid di-Me ester (I) with 1-pyrrolidinecarbonitrile (II) gave (pyrrolidinyl)cyclopenta[c]pyridine-6,6-dicarboxylic acid (III).

Chemical Communications (Cambridge, United Kingdom) published new progress about 2451-91-4. 2451-91-4 belongs to amides-buliding-blocks, auxiliary class Nitrile,Amine,Benzene, name is N,N-Dibenzylcyanamide, and the molecular formula is C15H14N2, Application of N,N-Dibenzylcyanamide.

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

Wu, Yueming published the artcileLithium hexamethyldisilazide initiated superfast ring opening polymerization of alpha-amino acid N-carboxyanhydrides, Application of H-Lys(Boc)-OH, the publication is Nature Communications (2018), 9(1), 5297, database is CAplus and MEDLINE.

Polypeptides have broad applications and can be prepared via ring-opening polymerization of α-amino acid N-carboxyanhydrides (NCAs). Conventional initiators, such as primary amines, give slow NCA polymerization, which requires multiple days to reach completion and can result in substantial side reactions, especially for very reactive NCAs. Moreover, current NCA polymerizations are very sensitive to moisture and must typically be conducted in a glove box. Here we show that lithium hexamethyldisilazide (LiHMDS) initiates an extremely rapid NCA polymerization process that is completed within minutes or hours and can be conducted in an open vessel. Polypeptides with variable chain length (DP = 20-1294) and narrow mol. weight distribution (Mw/Mn = 1.08-1.28) were readily prepared with this approach. Mechanistic studies support an anionic ring opening polymerization mechanism. This living NCA polymerization method allowed rapid synthesis of polypeptide libraries for high-throughput functional screening.

Nature Communications published new progress about 2418-95-3. 2418-95-3 belongs to amides-buliding-blocks, auxiliary class Chiral,Carboxylic acid,Amine,Aliphatic hydrocarbon chain,Ester,Amino acide derivatives, name is H-Lys(Boc)-OH, and the molecular formula is C10H18O, Application of H-Lys(Boc)-OH.

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

Fellah, Noalle published the artcileHighly Polymorphous Nicotinamide and Isonicotinamide: Solution versus Melt Crystallization, Name: Isonicotinamide, the publication is Crystal Growth & Design (2021), 21(8), 4713-4724, database is CAplus.

The crystallization of nicotinamide (NA) and its constitutional isomer, isonicotinamide (INA), is compared. NA formed eight polymorphs from the melt and two from solution, whereas INA formed two polymorphs from the melt and six from solution This anal. was provoked by the observation that NA is highly polymorphic from the melt, while the closely related INA is highly polymorphous from solution A combination of hot stage polarized light microscopy, powder X-ray diffraction, and Raman spectroscopy revealed that the polymorph selectivities are not related to supramol. self-association in the growth media. The larger estimated free energy gap separating NA polymorphs, compared with that of the INA polymorphs, is consistent with the smaller number of NA polymorphs generated from solution Phenomenol. analyses of crystallization kinetics suggest that cross nucleation is the most likely reason more polymorphs of NA than INA crystallize from the melt.

Crystal Growth & Design published new progress about 1453-82-3. 1453-82-3 belongs to amides-buliding-blocks, auxiliary class Pyridine,Amine,Amide, name is Isonicotinamide, and the molecular formula is C6H6N2O, Name: Isonicotinamide.

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

Liu, Qianqian published the artcileSH2 Domain-Containing Phosphatase 2 Inhibition Attenuates Osteoarthritis by Maintaining Homeostasis of Cartilage Metabolism via the Docking Protein 1/Uridine Phosphorylase 1/Uridine Cascade, Product Details of C17H14F3N3O2S, the publication is Arthritis & Rheumatology (2022), 74(3), 462-474, database is CAplus and MEDLINE.

Protein tyrosine kinases regulate osteoarthritis (OA) progression by activating a series of signal transduction pathways. However, the roles of protein tyrosine phosphatases (PTPs) in OA remain obscure. This study was undertaken to identify specific PTPs involved in OA and investigate their underlying mechanisms. The expression of 107 PTP genes in human OA cartilage was analyzed based on a single-cell sequencing data set. The enzyme activity of the PTP SH2 domain-containing phosphatase 2 (SHP-2) was detected in primary chondrocytes after interleukin-1β (IL-1β) treatment and in human OA cartilage. Mice subjected to destabilization of the medial meniscus (DMM) and IL-1β-stimulated mouse primary chondrocytes were treated with an SHP-2 inhibitor or celecoxib (a drug used for the clin. treatment of OA). The function of SHP-2 in OA pathogenesis was further verified in Aggrecan-CreERT;SHP2flox/flox mice. The downstream protein expression profile and dephosphorylated substrate of SHP-2 were examined by tandem mass tag labeling-based global proteomic anal. and stable isotope labeling with amino acids in cell culture-labeled tyrosine phosphoproteomic anal., resp. SHP-2 enzyme activity significantly increased in human OA samples with serious articular cartilage injury and in IL-1β-stimulated mouse chondrocytes. Pharmacol. inhibition or genetic deletion of SHP-2 ameliorated OA progression. SHP-2 inhibitors dramatically reduced the expression of cartilage degradation-related genes and simultaneously promoted the expression of cartilage synthesis-related genes. Mechanistically, SHP-2 inhibition suppressed the dephosphorylation of docking protein 1 and subsequently reduced the expression of uridine phosphorylase 1 and increased the uridine level, thereby contributing to the homeostasis of cartilage metabolism Conclusion : SHP-2 is a novel accelerator of the imbalance in cartilage homeostasis. Specific inhibition of SHP-2 may ameliorate OA by maintaining the anabolic-catabolic balance.

Arthritis & Rheumatology published new progress about 169590-42-5. 169590-42-5 belongs to amides-buliding-blocks, auxiliary class Sulfamide,Immunology/Inflammation,COX, name is 4-(5-(p-Tolyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)benzenesulfonamide, and the molecular formula is C17H14F3N3O2S, Product Details of C17H14F3N3O2S.

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