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.
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