Gaugaz, Fabienne Zdenka; Chicca, Andrea; Redondo-Horcajo, Mariano; Barasoain, Isabel; Fernando Diaz, J.; Altmann, Karl-Heinz published the artcile< Synthesis, microtubule-binding affinity, and antiproliferative activity of new epothilone analogs and of an EGFR-targeted epothilone-peptide conjugate>, Application In Synthesis of 2127-03-9, the main research area is colorectal adenocarcinoma EGFR microtubule binding affinity antiproliferative; cancer; drug discovery; epothilone; medicinal chemistry; microtubule-stabilizing agents; prodrug; total synthesis; tumor-targeting.
A new simplified, epoxide-free epothilone analog was prepared incorporating an N-(2-hydroxyethyl)-benzimidazole side chain, which binds to microtubules with high affinity and inhibits cancer cell growth in vitro with nM potency. Building on this scaffold, a disulfide-linked conjugate with the purported EGFR-binding (EGFR, epidermal growth factor receptor) peptide GE11 was then prepared The conjugate retained significant microtubule-binding affinity, in spite of the size of the peptide attached to the benzimidazole side chain. The antiproliferative activity of the conjugate was significantly lower than for the parent scaffold and, surprisingly, was independent of the EGFR expression status of cells. Our data indicate that the disulfide-based conjugation with the GE11 peptide is not a viable approach for effective tumor-targeting of highly potent epothilones and probably not for other cytotoxics.
International Journal of Molecular Sciences published new progress about Affinity (binding). 2127-03-9 belongs to class pyridine-derivatives, and the molecular formula is C10H8N2S2, Application In Synthesis of 2127-03-9.