Category: 10378-06-0

Kuruvilla, Sibu P. published the artcileEffect of N-acetylgalactosamine ligand valency on targeting dendrimers to hepatic cancer cells, COA of Formula: C14H19NO8, the publication is International Journal of Pharmaceutics (Amsterdam, Netherlands) (2018), 545(1-2), 27-36, database is CAplus and MEDLINE.

The display of N-acetylgalactosamine (NAcGal) ligands has shown great potential in improving the targeting of various therapeutic mols. to hepatocellular carcinoma (HCC), a severe disease whose clin. treatment is severely hindered by limitations in delivery of therapeutic cargo. We previously used the display of NAcGal on generation 5 (G5) polyamidoamine (PAMAM) dendrimers connected through a poly(ethylene glycol) (PEG) brush (i.e. G5-cPEG-NAcGal; monoGal) to effectively target hepatic cancer cells and deliver a loaded therapeutic cargo. In this study, we were interested to see if tri-valent NAcGal ligands (i.e. NAcGal₃) displayed on G5 dendrimers (i.e. G5-cPEG-NAcGal₃; triGal) could improve their ability to target hepatic cancer cells compared to their monoGal counterparts. We therefore synthesized a library of triGal particles, with either 2, 4, 6, 8, 11, or 14 targeting branches (i.e. cPEG-NAcGal₃) attached. Conventional flow cytometry studies showed that all particle formulations can label hepatic cancer cells in a concentration-dependent manner, reaching 90-100% of cells labeled at either 285 or 570 nM G5, but interestingly, monoGal labeled more cells at lower concentrations To elucidate the difference in internalization of monoGal vs. triGal conjugates, we turned to multi-spectral imaging flow cytometry and quantified the amount of internalized (I) vs. surface-bound (I⁰) conjugates to determine the ratio of internalization (I/I⁰) in all treatment groups. Results show that regardless of NAcGal valency, or the d. of targeting branches, all particles achieve full internalization and diffuse localization throughout the cell (I/I⁰ âˆ?3.0 for all particle compositions). This indicates that while tri-valent NAcGal is a promising technique for targeting nanoparticles to hepatic cancer cells, mono-valent NAcGal is more efficient, contrary to what is observed with small mols.

International Journal of Pharmaceutics (Amsterdam, Netherlands) published new progress about 10378-06-0. 10378-06-0 belongs to esters-buliding-blocks, auxiliary class Other Aliphatic Heterocyclic,Chiral,Ester,Inhibitor,Inhibitor, name is (3aR,5R,6R,7R,7aR)-5-(Acetoxymethyl)-2-methyl-5,6,7,7a-tetrahydro-3aH-pyrano[3,2-d]oxazole-6,7-diyl diacetate, and the molecular formula is C14H19NO8, COA of Formula: C14H19NO8.

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

Kuruvilla, Sibu P. published the artcileN-Acetylgalactosamine-Targeted Delivery of Dendrimer-Doxorubicin Conjugates Influences Doxorubicin Cytotoxicity and Metabolic Profile in Hepatic Cancer Cells, HPLC of Formula: 10378-06-0, the publication is Advanced Healthcare Materials (2017), 6(5), n/a, database is CAplus and MEDLINE.

This study describes the development of targeted, doxorubicin (DOX)-loaded generation 5 (G5) polyamidoamine dendrimers able to achieve cell-specific DOX delivery and release into the cytoplasm of hepatic cancer cells. G5 is functionalized with poly(ethylene glycol) (PEG) brushes displaying N-acetylgalactosamine (NAcGal) ligands to target hepatic cancer cells. DOX is attached to G5 through one of two aromatic azo-linkages, L3 or L4, achieving either P1 ((NAcGal_β-PEGc)_16.6-G5-(L3-DOX)_11.6) or P2 ((NAcGal_β-PEGc)_16.6-G5-(L4-DOX)_13.4) conjugates. After confirming the conjugatesâ€?biocompatibility, flow cytometry studies show P1/P2 achieve 100% uptake into hepatic cancer cells at 30-60 × 10^-9 M particle concentration This internalization correlates with cytotoxicity against HepG2 cells with 50% inhibitory concentration (IC₅₀) values of 24.8, 1414.0, and 237.8 × 10^-9 M for free DOX, P1, and P2, resp. Differences in cytotoxicity prompted metabolomics anal. to identify the intracellular release behavior of DOX. Results show that P1/P2 release alternative DOX metabolites than free DOX. Stable isotope tracer studies show that the different metabolites induce different effects on metabolic cycles. Namely, free DOX reduces glycolysis and increases fatty acid oxidation, while P1/P2 increase glycolysis, likely as a response to high oxidative stress. Overall, P1/P2 conjugates offer a platform drug delivery technol. for improving hepatic cancer therapy.

Advanced Healthcare Materials published new progress about 10378-06-0. 10378-06-0 belongs to esters-buliding-blocks, auxiliary class Other Aliphatic Heterocyclic,Chiral,Ester,Inhibitor,Inhibitor, name is (3aR,5R,6R,7R,7aR)-5-(Acetoxymethyl)-2-methyl-5,6,7,7a-tetrahydro-3aH-pyrano[3,2-d]oxazole-6,7-diyl diacetate, and the molecular formula is C14H19NO8, HPLC of Formula: 10378-06-0.

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

Szlag, Victoria M. published the artcileSERS Detection of Ricin B-Chain via N-Acetyl-Galactosamine Glycopolymers, Product Details of C14H19NO8, the publication is ACS Sensors (2016), 1(7), 842-846, database is CAplus.

A novel sensing scheme is exemplified through the detection of ricin B-chain (RBC) in water and liquid food matrixes: surface-enhanced Raman spectroscopy (SERS) coupled with an N-acetyl-galactosamine glycopolymer capture layer. The sensing scheme’s detection limit was well below that of the predicted oral exposure limit. Theor. predictions of the normal Raman spectrum of the glycomonomer give insight into polymer-RBC intermol. interactions.

ACS Sensors published new progress about 10378-06-0. 10378-06-0 belongs to esters-buliding-blocks, auxiliary class Other Aliphatic Heterocyclic,Chiral,Ester,Inhibitor,Inhibitor, name is (3aR,5R,6R,7R,7aR)-5-(Acetoxymethyl)-2-methyl-5,6,7,7a-tetrahydro-3aH-pyrano[3,2-d]oxazole-6,7-diyl diacetate, and the molecular formula is C7H6O3, Product Details of C14H19NO8.

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

Su, Timothy A. published the artcileA Modular Ionophore Platform for Liver-Directed Copper Supplementation in Cells and Animals, Name: (3aR,5R,6R,7R,7aR)-5-(Acetoxymethyl)-2-methyl-5,6,7,7a-tetrahydro-3aH-pyrano[3,2-d]oxazole-6,7-diyl diacetate, the publication is Journal of the American Chemical Society (2018), 140(42), 13764-13774, database is CAplus and MEDLINE.

Copper deficiency is implicated in a variety of genetic, neurol., cardiovascular, and metabolic diseases. Current approaches for addressing copper deficiency rely on generic copper supplementation, which can potentially lead to detrimental off-target metal accumulation in unwanted tissues and subsequently trigger oxidative stress and damage cascades. Here we present a new modular platform for delivering metal ions in a tissue-specific manner and demonstrate liver-targeted copper supplementation as a proof of concept of this strategy. Specifically, we designed and synthesized an N-acetylgalactosamine-functionalized ionophore, Gal-Cu(gtsm), to serve as a copper-carrying “Trojan Horse” that targets liver-localized asialoglycoprotein receptors (ASGPRs) and releases copper only after being taken up by cells, where the reducing intracellular environment triggers copper release from the ionophore. We utilized a combination of bioluminescence imaging and inductively coupled plasma mass spectrometry assays to establish ASGPR-dependent copper accumulation with this reagent in both liver cell culture and mouse models with minimal toxicity. The modular nature of our synthetic approach presages that this platform can be expanded to deliver a broader range of metals to specific cells, tissues, and organs in a more directed manner to treat metal deficiency in disease.

Journal of the American Chemical Society published new progress about 10378-06-0. 10378-06-0 belongs to esters-buliding-blocks, auxiliary class Other Aliphatic Heterocyclic,Chiral,Ester,Inhibitor,Inhibitor, name is (3aR,5R,6R,7R,7aR)-5-(Acetoxymethyl)-2-methyl-5,6,7,7a-tetrahydro-3aH-pyrano[3,2-d]oxazole-6,7-diyl diacetate, and the molecular formula is C19H24BNO2, Name: (3aR,5R,6R,7R,7aR)-5-(Acetoxymethyl)-2-methyl-5,6,7,7a-tetrahydro-3aH-pyrano[3,2-d]oxazole-6,7-diyl diacetate.

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

Yamamoto, Tsuyoshi published the artcileSerial incorporation of a monovalent GalNAc phosphoramidite unit into hepatocyte-targeting antisense oligonucleotides, SDS of cas: 10378-06-0, the publication is Bioorganic & Medicinal Chemistry (2016), 24(1), 26-32, database is CAplus and MEDLINE.

The targeting of abundant hepatic asialoglycoprotein receptors (ASGPR) with trivalent N-acetylgalactosamine (GalNAc) is a reliable strategy for efficiently delivering antisense oligonucleotides (ASOs) to the liver. The authors here exptl. demonstrate the high systemic potential of the synthetically-accessible, phosphodiester-linked monovalent GalNAc unit when tethered to the 5′-terminus of well-characterized 2′,4′-bridged nucleic acid (also known as locked nucleic acid)-modified apolipoprotein B-targeting ASO via a bio-labile linker. Quant. anal. of the hepatic disposition of the ASOs revealed that phosphodiester is preferable to phosphorothioate as an interunit linkage in terms of ASGPR binding of the GalNAc moiety, as well as the subcellular behavior of the ASO. The flexibility of this monomeric unit was demonstrated by attaching up to 5 GalNAc units in a serial manner and showing that knockdown activity improves as the number of GalNAc units increases. The authors’ study suggests the structural requirements for efficient hepatocellular targeting using monovalent GalNAc and could contribute to a new mol. design for suitably modifying ASO.

Bioorganic & Medicinal Chemistry published new progress about 10378-06-0. 10378-06-0 belongs to esters-buliding-blocks, auxiliary class Other Aliphatic Heterocyclic,Chiral,Ester,Inhibitor,Inhibitor, name is (3aR,5R,6R,7R,7aR)-5-(Acetoxymethyl)-2-methyl-5,6,7,7a-tetrahydro-3aH-pyrano[3,2-d]oxazole-6,7-diyl diacetate, and the molecular formula is C7H5Cl2NO, SDS of cas: 10378-06-0.

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

Reina, Jose J. published the artcileGlycosyl Aldehydes: New Scaffolds for the Synthesis of Neoglycoconjugates via Bioorthogonal Oxime Bond Formation, Formula: C14H19NO8, the publication is Synthesis (2018), 50(4), 831-845, database is CAplus.

The straightforward preparation of glycosyl neoconjugates by oxime (or hydrazone) bond formation represents a key bioorthogonal tool in chem. biol. However, when this strategy is employed by reacting the reducing end of the glycan moiety, the configuration and the stereochem. information is lost due to partial (or complete) opening of the glycan cyclic hemiacetal and the formation of the corresponding opened tautomers. We have completed the synthesis of a library of glycosyl aldehydes to be used as scaffold for the synthesis of neoglycoconjugates via oxime bond formation. These glycosyl aldehydes constitute a simple and accessible alternative to avoid loss of chiral information when conjugating, by oxime (or hydrazone) bonds, the aldehyde functionality present at the reducing end of natural carbohydrates.

Synthesis published new progress about 10378-06-0. 10378-06-0 belongs to esters-buliding-blocks, auxiliary class Other Aliphatic Heterocyclic,Chiral,Ester,Inhibitor,Inhibitor, name is (3aR,5R,6R,7R,7aR)-5-(Acetoxymethyl)-2-methyl-5,6,7,7a-tetrahydro-3aH-pyrano[3,2-d]oxazole-6,7-diyl diacetate, and the molecular formula is C14H19NO8, Formula: C14H19NO8.

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

Ivanenkov, Yan A. published the artcileSynthesis and biological evaluation of novel doxorubicin-containing ASGP-R-targeted drug-conjugates, HPLC of Formula: 10378-06-0, the publication is Bioorganic & Medicinal Chemistry Letters (2018), 28(3), 503-508, database is CAplus and MEDLINE.

Asialoglycoprotein receptor (ASGP-R) belongs to a wide family of C-type lectins and it is currently regarded as an attractive protein in the field of targeted drug delivery (TDD). It is abundantly expressed in hepatocytes and can be found predominantly on the sinusoidal surface especially of HepG2 cells. Therefore, ASGP-R can be used for the TDD of anticancer therapeutics against HCC and mol. diagnostic tools. To date, a variety of mono- and multivalent selective ASGP-R ligands have been discovered. Although many of these compounds have demonstrated a relatively high binding affinity towards the target, the reported synthetic schemes are not handled, complicated and include many non-trivial steps. In the current study, we describe a convenient and versatile synthetic approach to novel monovalent drug-conjugates containing N-acetyl-2-deoxy-2-aminogalactopyranose fragment as an ASGP-R-recognition “core-head” and well-known nonselective cytostatic – Doxorubicin (Dox). This is the first example of the direct conjugation of a drug mol. to the ASGP-targeted warhead by a really convenient manner via a simple linker sequence. The performed MTS-based biol. evaluation in HepG2 cells revealed the novel conjugates as having anticancer activity. Confocal microscopy showed that the mols. readily penetrated HepG2 membrane and were mainly localized within the cytoplasm instead of the nucleus. Per contra, Dox under the same conditions demonstrated good anticancer activity and was predominantly concentrated in the nucleus. Therefore, we speculate that the amide “trigger” that we have used in this study for linker attachment is a sufficiently stable inside the cells to be enzymically or spontaneously degraded. As a consequence, we did not observe the release of the drug. Ligands containing triggers that are more liable towards endogenous hydrolysis within the tissue of targeting are strongly required.

Bioorganic & Medicinal Chemistry Letters published new progress about 10378-06-0. 10378-06-0 belongs to esters-buliding-blocks, auxiliary class Other Aliphatic Heterocyclic,Chiral,Ester,Inhibitor,Inhibitor, name is (3aR,5R,6R,7R,7aR)-5-(Acetoxymethyl)-2-methyl-5,6,7,7a-tetrahydro-3aH-pyrano[3,2-d]oxazole-6,7-diyl diacetate, and the molecular formula is C14H19NO8, HPLC of Formula: 10378-06-0.

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

Petrov, Rostislav A. published the artcileSynthesis and biological evaluation of novel mono- and bivalent ASGP-R-targeted drug-conjugates, Safety of (3aR,5R,6R,7R,7aR)-5-(Acetoxymethyl)-2-methyl-5,6,7,7a-tetrahydro-3aH-pyrano[3,2-d]oxazole-6,7-diyl diacetate, the publication is Bioorganic & Medicinal Chemistry Letters (2018), 28(3), 382-387, database is CAplus and MEDLINE.

Asialoglycoprotein receptor (ASGP-R) is a promising biol. target for drug delivery into hepatoma cells. Nevertheless, there are only few examples of small-mol. conjugates of ASGP-R selective ligand equipped by a therapeutic agent for the treatment of hepatocellular carcinoma (HCC). In the present work, we describe a convenient and versatile synthetic approach to novel mono- and multivalent drug-conjugates containing N-acetyl-2-deoxy-2-aminogalactopyranose and anticancer drug – paclitaxel (PTX). Several mols. have demonstrated high affinity towards ASGP-R and good stability under physiol. conditions, significant in vitro anticancer activity comparable to PTX, as well as good internalization via ASGP-R-mediated endocytosis. Therefore, the conjugates with the highest potency can be regarded as a promising therapeutic option against HCC.

Bioorganic & Medicinal Chemistry Letters published new progress about 10378-06-0. 10378-06-0 belongs to esters-buliding-blocks, auxiliary class Other Aliphatic Heterocyclic,Chiral,Ester,Inhibitor,Inhibitor, name is (3aR,5R,6R,7R,7aR)-5-(Acetoxymethyl)-2-methyl-5,6,7,7a-tetrahydro-3aH-pyrano[3,2-d]oxazole-6,7-diyl diacetate, and the molecular formula is C14H19NO8, Safety of (3aR,5R,6R,7R,7aR)-5-(Acetoxymethyl)-2-methyl-5,6,7,7a-tetrahydro-3aH-pyrano[3,2-d]oxazole-6,7-diyl diacetate.

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

Agramunt, Jordi published the artcileInverse Electron-Demand Diels-Alder Bioconjugation Reactions Using 7-Oxanorbornenes as Dienophiles, Application of (3aR,5R,6R,7R,7aR)-5-(Acetoxymethyl)-2-methyl-5,6,7,7a-tetrahydro-3aH-pyrano[3,2-d]oxazole-6,7-diyl diacetate, the publication is Journal of Organic Chemistry (2020), 85(10), 6593-6604, database is CAplus and MEDLINE.

Oligonucleotides, peptides, and peptide nucleic acids incorporating 7-oxanorbornene as a dienophile were reacted with tetrazines linked to either a peptide, D-biotin, BODIPY, or N-acetyl-D-galactosamine. The inverse electron-demand Diels-Alder (IEDDA) cycloaddition, which was performed overnight at 37°C, in all cases furnished the target conjugate in good yields. IEDDA reactions with 7-oxanorbornenes produce a lower number of stereoisomers than that of IEDDA cycloadditions with other dienophiles.

Journal of Organic Chemistry published new progress about 10378-06-0. 10378-06-0 belongs to esters-buliding-blocks, auxiliary class Other Aliphatic Heterocyclic,Chiral,Ester,Inhibitor,Inhibitor, name is (3aR,5R,6R,7R,7aR)-5-(Acetoxymethyl)-2-methyl-5,6,7,7a-tetrahydro-3aH-pyrano[3,2-d]oxazole-6,7-diyl diacetate, and the molecular formula is C14H19NO8, Application of (3aR,5R,6R,7R,7aR)-5-(Acetoxymethyl)-2-methyl-5,6,7,7a-tetrahydro-3aH-pyrano[3,2-d]oxazole-6,7-diyl diacetate.

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

Wipf, Peter published the artcileSynthesis of anti-inflammatory α- and β-linked acetamido pyranosides as inhibitors of toll-like receptor 4 (TLR4), Formula: C14H19NO8, the publication is Tetrahedron Letters (2015), 56(23), 3097-3100, database is CAplus and MEDLINE.

The low-mol.-weight iso-Pr 2-acetamido-α-glucoside I (R = AcO, R¹ = H; (C34)) inhibits toll-like receptor 4 (TLR4) in enterocytes and macrophages in vitro, and reduces systemic inflammation in mouse models of endotoxemia and necrotizing enterocolitis. The authors used a Cu(II)-mediated solvolysis of anomeric oxazolines and an acid-mediated conversion of β-glucosamine- and β-galactosamine pentaacetates to generate analogs of C34 at the anomeric C and at C(4) of the pyranose ring. These compounds were evaluated for their effect on TLR4-mediated inflammatory signaling in cultured enterocytes and monocytes. Their efficacy was confirmed using a NF-κB-luciferase reporter mouse, thus establishing a structure-activity relationship (SAR) study in this series and identifying the more efficacious iso-Pr 2-acetamido-α-galactoside I (R = H, R¹ = AcO).

Tetrahedron Letters published new progress about 10378-06-0. 10378-06-0 belongs to esters-buliding-blocks, auxiliary class Other Aliphatic Heterocyclic,Chiral,Ester,Inhibitor,Inhibitor, name is (3aR,5R,6R,7R,7aR)-5-(Acetoxymethyl)-2-methyl-5,6,7,7a-tetrahydro-3aH-pyrano[3,2-d]oxazole-6,7-diyl diacetate, and the molecular formula is C4Br2N2O4S, Formula: C14H19NO8.

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