National Institutes of Health, a Component of the US Dept. of Health & Human Services

Robert W Robey

Susan Elaine Bates

Michael C Dean

James Brislin McMahon

Curtis J Henrich

Heidi R Bokesch

Suneet Shukla

Suresh V Ambudkar

Kirk R Gustafson

Richard W Fuller

Kentaro Takada

Laura K Cartner

Disclosed are methods of enhancing the chemotherapeutic treatment of tumor cells, reducing resistance of a cancer cell to a chemotherapeutic agent, a method of inhibiting ABCG2 or MRP1 in a mammal afflicted with cancer, and a method of increasing the bioavailability of an ABCG2 substrate drug in a mammal. The methods comprise administering peliomycin and other compounds described herein.

Method of inhibiting ABCG2 and related treatments

Disclosed are methods of enhancing the chemotherapeutic treatment of tumor cells, reducing resistance of a cancer cell to a chemotherapeutic agent, a method of inhibiting ABCG2, Pgp, or MRP1 in a mammal afflicted with cancer, and a method of increasing the bioavailability of an ABCG2 substrate drug in a mammal. The methods comprise administering effective amounts of certain compounds to the mammal, for example, a compound of the formula (I): wherein R, R, R, X, X, X, a, and b are as described herein. Uses of these compounds in the preparation of a medicament are also disclosed. Also disclosed are compounds of formula (II), pharmaceutical compositions comprising such compounds and uses thereof.

Method of inhibiting ABCG2 and other treatment methods

Disclosed are methods of enhancing the chemotherapeutic treatment of tumor cells, reducing resistance of a cancer cell to a chemotherapeutic agent, a method of inhibiting ABCG2, Pgp, or MRP1 in a mammal afflicted with cancer, and a method of increasing the bioavailability of an ABCG2 substrate drug in a mammal. The methods comprise administering effective amounts of certain compounds to the mammal, for example, a compound of the formula (I): Formula (I), wherein R, R, R, X, X, X, a, and b are as described herein. Uses of these compounds in the preparation of a medicament are also disclosed. Also disclosed are compounds of formula (II), pharmaceutical compositions comprising such compounds and uses thereof. 

Botryllamides and method of inhibiting PGP in a mammal afflicted with cancer

This invention provides methods that are useful for inhibiting a MXR transporter in a cell overexpressing a MXR gene but not overexpressing a Pgp gene by contacting the cell with an acridine derivative. The invention also provides for a method of treating a mammal suffering from a cancer, which overexpressing a MXR gene but not overexpress a Pgp gene, by the co-administration of a chemotherapeutic and an acridine derivative.

Inhibition of MXR transport by acridine derivatives

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Laurel, MD, United States of America

Robert W Robey