title: Design and regioselective synthesis of a new generation of targeted chemotherapeutics. Part 1: EC145, a folic acid conjugate of desacetylvinblastine monohydrazide.
abstract: An efficient synthesis of the folate receptor (FR) targeting conjugate EC145 is described. EC145 is a water soluble derivative of the vitamin folic acid and the potent cytotoxic agent, desacetylvinblastine monohydrazide. Both molecules are connected in regioselective manner via a hydrophilic peptide spacer and a reductively labile disulfide linker.
authors.affiliation: Endocyte Inc., 3000 Kent Ave, Suite A1-100, West Lafayette, IN 47906, USA. ivlahov@endocyte.com
authors.forename: Iontcho R
authors.initials: IR
authors.lastname: Vlahov
authors.forename: Hari Krishna R
authors.initials: HK
authors.lastname: Santhapuram
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Kleindl
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Howard
authors.forename: Katheryn M
authors.initials: KM
authors.lastname: Stanford
authors.forename: Christopher P
authors.initials: CP
authors.lastname: Leamon
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000633:toxicity; D004220:Disulfides / Q000737:chemistry; D016503:Drug Delivery Systems; D015195:Drug Design; D005492:Folic Acid / Q000138:chemical synthesis* / Q000494:pharmacology; D012995:Solubility; D013329:Structure-Activity Relationship; D014747:Vinblastine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D004220:Disulfides; C055170:4-desacetylvinblastine hydrazide; D014747:Vinblastine; D005492:Folic Acid