The present invention provides pharmaceutical compositions comprising derivatives of NDGA, including M4N (tetra-O-methyl nordihydroguaiaretic acid) and sorafenib and their use in the inhibition and treatment of neoplastic diseases, such as liver cancer, colon cancer, breast cancer, brain cancers and ovarian cancers, for example, in a subject. Compositions comprising derivatives of NDGA, including M4N, sorafenib and additional therapeutic agents are also provided.

THE JOHNS HOPKINS UNIVERSITY

The Johns Hopkins University

Compositions comprising NDGA derivatives and sorafenib and their use in treatment of cancer

Novel compounds which are derivatives of tetra-O-methyl nordihydroguaiaretic acid (NDGA), as well as pharmaceutically acceptable salts, solvates, and stereoisomers thereof are provided. These NDGA derivatives have a nitroimidazole moiety and these derivatives show preferential toxicity to hypoxic cells as hypoxic cytotoxins. Their cytotoxicity toward hypoxic cells is a result of abstraction of hydrogen from target molecules by free radicals formed in the reduction of the nitro group. This makes the disclosed compounds an effective anti cancer drug because hypoxic cells are generally considered to be more resistant to anti cancer drugs than normal cells. Pharmaceutical compositions comprising such compounds, as well as methods of use, and treatment for cancers, including hepatocellular carcinoma, breast cancer and prostate cancer, are also provided.

nordihydroguaiaretic acid/breast neoplasms

Compositions comprising NDGA derivatives and sorafenib and their use in treatment of cancer

Conjugates of nitroimidazoles and their use as chemotherapeutic agents

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