Thiabaud, Gregory; He, Guangan; Sen, Sajal; Shelton, Kathryn A.; Baze, Wallace B.; Segura, Luke; Alaniz, Julie; Macias, Ruben Munoz; Lyness, Greg; Watts, Alan B.; Kim, Hyun Min; Lee, Hyunseung; Cho, Mi Young; Hong, Kwan Soo; Finch, Rick; Siddik, Zahid H.; Arambula, Jonathan F.; Sessler, Jonathan L. published the artcile< Oxaliplatin Pt(IV) prodrugs conjugated to gadolinium-texaphyrin as potential antitumor agents>, Computed Properties of 128-09-6, the main research area is preparation oxaliplatin prodrug conjugate gadolinium texaphyrin antitumor drug resistance; cancer; drug development; drug resistance; platinum prodrug; texaphyrins.
Described here is the development of gadolinium(III) texaphyrin-platinum(IV) conjugates capable of overcoming platinum resistance by 1) localizing to solid tumors, 2) promoting enhanced cancer cell uptake, and 3) reactivating p53 in platinum-resistant models. Side by side comparative studies of these Pt(IV) conjugates to clin. approved platinum(II) agents and previously reported platinum(II)-texaphyrin conjugates demonstrate that the present Pt(IV) conjugates are more stable against hydrolysis and nucleophilic attack. Moreover, they display high potent antiproliferative activity in vitro against human and mouse cell cancer lines. Relative to the current platinum clin. standard of care (SOC), a lead Gd(III) texaphyrin-Pt(IV) prodrug conjugate emerging from this development effort was found to be more efficacious in s.c. mouse models involving both cell-derived xenografts and platinum-resistant patient-derived xenografts. Comparative pathol. studies in mice treated with equimolar doses of the lead Gd texaphyrin-Pt(IV) conjugate or the US Food and Drug Administration (FDA)-approved agent oxaliplatin revealed that the conjugate was better tolerated. Specifically, the lead could be dosed at more than three times (i.e., 70 mg/kg per dose) the tolerable dose of oxaliplatin (i.e., 4 to 6 mg/kg per dose depending on the animal model) with little to no observable adverse effects. A combination of tumor localization, redox cycling, and reversible protein binding is invoked to explain the relatively increased tolerability and enhanced anticancer activity seen in vivo. On the basis of the present studies, we conclude that metallotexaphyrin-Pt conjugates may have substantial clin. potential as antitumor agents.
Proceedings of the National Academy of Sciences of the United States of America published new progress about Antitumor agent resistance (to platinum). 128-09-6 belongs to class chlorides-buliding-blocks, and the molecular formula is C4H4ClNO2, Computed Properties of 128-09-6.
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