148930-30-7Relevant articles and documents
Synthesis and biological evaluation of a biotinylated paclitaxel with an extra-long chain spacer arm
Lis, Lev. G.,Smart, Mary A.,Luchniak, Anna,Gupta, Mohan L.,Gurvich, Vadim J.
, p. 745 - 748 (2012/11/13)
A biotinylated paclitaxel derivative with an extra-long chain (LC-LC-biotin) spacer arm was synthesized using an improved synthetic reaction sequence. The biotinylated paclitaxel analogue retained excellent microtubule stabilizing activity in vitro. Furth
Modulating paclitaxel bioavailability for targeting prostate cancer
Kumar, Srinivas K.,Williams, Simon A.,Isaacs, John T.,Denmeade, Samuel R.,Khan, Saeed R.
, p. 4973 - 4984 (2008/03/13)
Four novel water-soluble peptide-paclitaxel conjugates were designed and synthesized as prostate-specific antigen (PSA)-activated prodrugs for prostate cancer therapy. These prodrugs were composed of a peptide, HSSKLQ or SSKYQ, each of which is selectively cleavable by PSA; a self-immolative linker, either para-aminobenzyl alcohol (PABS) or ethylene diamine (EDA); and the parent drug, paclitaxel. Introduction of a PABA or EDA linker between the peptide and paclitaxel in prodrugs 2-5 resulted in products with an increased rate of hydrolysis by PSA. The stability of prodrugs 2 and 3, with the PABA linker, was poor in the serum-containing medium because of the weak carbonate bond between the PABA and paclitaxel; however, this disadvantage was overcome by introducing a carbamate bond using an EDA linker in prodrugs 4 and 5. Thus, the incorporation of an EDA linker increased both the stability and PSA-mediated activation of these prodrugs. The cytotoxicity of each prodrug, as compared to paclitaxel, was determined against a variety of cell lines, including the PSA-secreting CWR22Rv1 prostate cancer cell line. The EDA-derived prodrug of paclitaxel 5 was stable and capable of being efficiently converted to an active drug that killed cells specifically in the presence of PSA, suggesting that this prodrug and similarly designed PSA-cleavable prodrugs may have potential as prostate cancer-specific therapeutic agents.
Paclitaxel delivery systems: The use of amino acid linkers in the conjugation of paclitaxel with carboxymethyldextran to create prodrugs
Sugahara, Shu-Ichi,Kajiki, Masahiro,Kuriyama, Hiroshi,Kobayashi, To-Ru
, p. 632 - 641 (2007/10/03)
Paclitaxel was bound via its hydroxyl group to carboxymethyldextran (CMDex, 150 kDa) by means of an amino acid linker; the linker was introduced into the 2′- or 7-hydroxyl group of the paclitaxel through an ester bond. These conjugates - CMDex-2′-paclitax
