Unique Platinum-based Chemotherapeutics to

Treat Drug Resistant Tumor Cells

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 Inventor: Ulrich Bierbach

TECHNOLOGY DESCRIPTION:

Researchers in the Department of Chemistry at Wake Forest University have developed a new class of platinum-acridine chemotherapeutics. Because of their novel drug–DNA interaction, these compounds exhibit a potent cytotoxic response in a tumor cell line previously shown to be difficult to kill by standard therapies (including platinum-based drugs). In addition, these compounds significantly slowed the progression of this aggressive form of cancer in vivo.

Unique Mechanism of Action

• novel platinum-based antineoplastics both bind to DNA at the platinum site as well as intercalate via the acridine moiety
• exhibits a unique pharmaceutical activity by rapidly binding and disrupting DNA in regions not targeted by cisplatin 
• these compounds do not induce cross-links (as seen in other platinumbased chemotherapeutics) and do not require hydrolytic activation prior to binding to their pharmacological target
• adducts may evade nucleotide excision repair process

High Efficacy

• novel platinum-based drugs were 10-fold more cytotoxic than cisplatin in H460 cell proliferation assays with IC50 values in the nanomolar range
• the new analogue significantly reduces H460 tumor growth in a xenograft model at doses an order of magnitude lower than those typically administered for cisplatin

ADDITIONAL INFORMATION:

J Med Chem. 2008, 51, 7574–7580

SciBX Cover Story “Expanding Platinum’s Potential”

Licensing Contact:

Stephen J. Susalka, Ph.D.

Assistant Director

Email: ssusalka@wfubmc.edu

Phone: (336) 716-3729