418 Recent Advances in the Biomedical Applications of Texaphryins

Friday, November 6, 2009: 11:10 AM
Rio Grande (Camino Real Hotel)
Jonathan F. Arambula , Department of Chemistry and Biochemistry, University of Texas at Austin, Austin, TX
Jonathan L. Sessler , Department of Chemistry and Biochemistry, University of Texas at Austin, Austin, TX
Mark Fountain , Department of Chemistry and Biochemistry, University of Texas at Austin, Austin, TX
Wen-hao Wei , Department of Chemistry and Biochemistry, University of Texas at Austin, Austin, TX
Darren Magda , Pharmacyclics, Inc., 995 E. Arques Ave., Sunnyvale, CA 94085, Sunnyvale, CA
Zahid H. Siddik , Experimental Therapeutics, University of Texas M. D. Anderson Cancer Center, Houston, TX
Texaphyrins are members of the “expanded porphyrin” class of macrocycles. These pentaaza analogues of porphyrins allow for the coordination of larger metal cations and have led to the development of what appear to be several well-tolerated experimental therapeutic agents. One of these, motexafin gadolinium (MGd), a specific gadolinium(III) texaphyrin (Gd-Tex) complex, has been the subject of several clinical trials, in which tumor localization was demonstrated by MRI.

The FDA-approved Pt(II)-based drugs cisplatin, carboplatin, and oxaliplatin, are mainstays in modern cancer chemotherapy. However, resistance to these agents is generally seen after initial treatments. This resistance often becomes dose-limiting and, in the case of NSCLC treatment, is manifest in a ca. 5% five-year survival rate. One way this resistance could be reduced or overcome would be through targeting the Pt complexes to cancerous lesions. With such a vision in mind, we have created several Gd-Tex Pt conjugates with the goal of improving the delivery and reducing the toxicity issues observed with cisplatin and other Pt(II) based therapeutics.  This presentation will provide a summary of efforts along these lines.