Novel Compounds that Specifically Kill Multi-Drug Resistant Cancer Cells

One of the major hindrances to successful cancer chemotherapy is the development of multi-drug resistance (MDR) in cancer cells. MDR is frequently caused by the increased expression or activity of ABC transporter proteins in response to the toxic agents used in chemotherapy. Research has generally been directed to overcoming MDR by inhibiting the activity of ABC transporters. However, compounds that inhibit ABC transporter activity often elicit strong and undesirable side-effects, restricting their usefulness as therapeutics.

Investigators at the NIH previously identified that the compound NSC73306 had the ability to specifically kill cancer cells that overexpressed an ABC transporter responsible for MDR. Importantly, this "MDR-selective compound" is not an inhibitor of ABC transporters, reducing the likelihood of undesirable side-effects if used as a therapeutic.

Using NSC 73306 as a model, new MDR-selective compounds have been created with improved solubility and selectivity. These new MDR-selective compounds can also selectively kill MDR cancer cells, with their efficacy correlating directly with the level of ABC transporter expression. Recent evidence also shows that these new MDR-selective compounds have the ability to decrease the expression of ABC transporters, potentially re-sensitizing the cancer cells to chemotherapeutic agents. Thus, MDR-selective compounds represent a powerful strategy for treating multi-drug resistant cancers as a direct chemotherapeutic and as agents that can re-sensitize MDR cancer cells for treatment with additional chemotherapeutic agents.

Potential Commercial Applications: Competitive Advantages:
  • Treatment of cancers associated with multi-drug resistance, either alone or in combination with other therapeutics
  • Development of a pharmacophore for improved effectiveness in treating cancers associated with multi-drug resistance
  • Re-sensitization of multi-drug resistant cancer cells to chemotherapeutic agents
  • MDR-selective compounds capitalize on one of the most common drawbacks to cancer therapies (MDR) by using it as an advantage for treating cancer
  • The compositions do not inhibit the activity of ABC transporters, thereby reducing the chance of undesired side-effects during treatment
  • The effects of MDR-selective compounds correlate with the level of ABC transporter expression, allowing healthy cells which do not express high levels of ABC transporters to better survive treatments
  • Increased specificity allows the new MDR-selective compounds to be tailored to treating cancers associated with the overexpression and hyperactivity of particular ABC transporters
  • Increased solubility of the new MDR-selective compounds allows greater access to cancer cells, thereby increasing therapeutic effectiveness

Development Stage:
Preclinical stage of development


Matthew Hall (NCI)  ➽ more inventions...

Intellectual Property:
US Application No. 61/027,712
PCT Application No. PCT/US2009/000861
US Application No. 12/867,206

Collaboration Opportunity:

The National Cancer Institute, Laboratory of Cell Biology, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize the agents described here. Please contact John D. Hewes, Ph.D. at 301-435-3121 or for more information.

Licensing Contact:
David Lambertson, Ph.D.
Phone: 240-276-6467

OTT Reference No: E-017-2008/0
Updated: Jul 2, 2009