title: Camptothecins in tumor homing via an RGD sequence mimetic.
abstract: A RGD peptide mimetic was conjugated to four camptothecins, with the purpose to improve their therapeutic index. The conjugate derivatives were evaluated against two tumor cell lines, one overexpressing integrins (human ovarian carcinoma, A2780) and a second one with a low integrin expression (human prostate cancer, PC3). The in vitro screening was completed with the adhesion behavior to vitronectin. Compound 8 (ST7456CL1) was selected for the in vivo investigation after stability tests over 24h, in PBS solution and in rat plasma, and compared to irinotecan. The former showed a prolonged half-life.
authors.affiliation: Corporate R&D, sigma-tau Industrie Farmaceutiche Riunite SpA, Pomezia, Italy.
authors.forename: Domenico
authors.initials: D
authors.lastname: Alloatti
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Giannini
authors.forename: Loredana
authors.initials: L
authors.lastname: Vesci
authors.forename: Massimo
authors.initials: M
authors.lastname: Castorina
authors.forename: Claudio
authors.initials: C
authors.lastname: Pisano
authors.forename: Elena
authors.initials: E
authors.lastname: Badaloni
authors.forename: Walter
authors.initials: W
authors.lastname: Cabri
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000494:pharmacology; D002166:Camptothecin / Q000008:administration & dosage* / Q000494:pharmacology; D045744:Cell Line, Tumor; D016503:Drug Delivery Systems; D005260:Female; D006801:Humans; D016023:Integrins / Q000276:immunology*; D008297:Male; D009842:Oligopeptides / Q000737:chemistry* / Q000276:immunology; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000276:immunology; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000276:immunology; D051381:Rats
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D016023:Integrins; D009842:Oligopeptides; C047981:arginyl-glycyl-aspartic acid; D002166:Camptothecin