title: SDZ 280-125: a cyclopeptolide endowed with an in vitro cyclosporin A-like profile of activity for the reversion of the P-glycoprotein-mediated multidrug resistance of tumor cells.
abstract: Tumor cells whose multidrug resistance is caused by the P-glycoprotein (Pgp) mediated anti-cancer drug (ACD) efflux can be chemosensitized by cyclosporins, whose derivatives were found to display a whole range of resistance-modulating activities. Similarly, derivatives of the non-immunosuppressive natural fungus cyclic peptolide SDZ 90-215 were recently shown to display a broad range of chemosensitizing activities. With highly resistant cells expressing high levels of Pgp, one such compound (SDZ 280-125) was shown here to restore both a normal sensitivity to the growth-inhibitory effects of ACD and a normal retention of an anthracycline antibiotic. With both read-outs, SDZ 280-125 activity was about 3-fold that of cyclosporin A (CsA). SDZ 280-125 also displayed the same profile of chemosensitization as CsA for different ACD classes.
authors.affiliation: Sandoz Pharma Ltd., Basel, Switzerland.
authors.forename: B
authors.initials: B
authors.lastname: Jachez
authors.forename: D
authors.initials: D
authors.lastname: Boesch
authors.forename: G
authors.initials: G
authors.lastname: Emmer
authors.forename: F
authors.initials: F
authors.lastname: Loor
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000502:physiology*; D000595:Amino Acid Sequence; D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D016572:Cyclosporine / Q000494:pharmacology; D003630:Daunorubicin / Q000493:pharmacokinetics / Q000494:pharmacology; D004347:Drug Interactions; D004351:Drug Resistance; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D007624:KB Cells; D007941:Leukemia P388 / Q000188:drug therapy / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D009374:Neoplasms, Experimental / Q000188:drug therapy* / Q000378:metabolism*; D010456:Peptides, Cyclic / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000187:drug effects
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D010456:Peptides, Cyclic; C089531:SDZ 280-125; D016572:Cyclosporine; D003630:Daunorubicin