Johns Hopkins University

Ru Chih Huang

Kotohiko Kimura

John N Gnabre

David Mold

Paul Edward Giza

Yu-Chuan Liang

Jong Ho Chun

Christopher Ruland

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.

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

Provided herein are methods for prevention and treatment of ischemia-reperfusion (IR) injury in the cardiac myocytes of a subject, by administration to the subject, a compound of formula I, or a salt, solvate, or stereoisomer thereof, in a sufficient amount either prior to, or during and/or after an ischemic event to mitigate or prevent IR injury to the cardiac tissue. Pharmaceutical compositions including the compound of formula I, or a salt, solvate, or stereoisomer thereof, and/or at least one additional therapeutic agent, are also provided.

Methods for inhibition of BNIP3 and prevention and treatment of ischemia reperfusion injury by tetra-O-methyl nordihydroguaiaretic acid

Disclosed is a composition comprising a derivative of NDGA and at least one metabolic modulator. The composition can be in a unit dose form or kit. The composition can comprise at least two metabolic modulators. Also disclosed are methods for achieving cytotoxicity, particularly of rapidly dividing cells such as cancer, by administering a composition of the invention. In various embodiments of the invention subjects with cancer achieve prolonged survival and/or diminution in the size of their malignancies and cancer metastasis.

Suppression of cancer growth and metastasis using nordihydroguaiaretic acid derivatives with metabolic modulators

The present invention reveals the isolation, purification and characterization from the creosote bush Larrea tridentata of compounds of the structural formula: ##STR1## where R.sub.1, R.sub.2, R.sub.3 and R.sub.4 are each selected from the group consisting of HO--, CH.sub.3 O-- and CH.sub.3 (C.dbd.O)O--, provided that R.sub.1, R.sub.2, R.sub.3 and R.sub.4 are not each HO-- simultaneously. Each compound is a derivative of 1,4-bis-(3,4-dihydroxyphenyl)-2,3-dimethylbutane (nordihydroquaiaretic acid, NDGA). In addition, NDGA and each derivative can be used in a method to suppress Tat transactivation of a lentivirus, including the HIV virus, in a cell by administering NDGA or a derivative of NDGA to the cell.

Compounds for the suppression of HIV Tat transactivation

Discoveries are disclosed that show that certain mutations in different parts of the mechanism for regulation of independently replicating element replication can be combined in one expression independently replicating element to produce a runaway-replication phenotype that is suppressible by a diffusible factor from another independently replicating element co-resident in the host cell. According to the present invention, an expression independently replicating element combining known inducible promoters with this runaway-replication phenotype is used in combination with a independently replicating element that suppresses this runaway phenotype to establish a gene expression system that provides both controllable gene amplification and controllable induction of gene expression without the use of chemical inducers or temperature shifts. This expression system produces high yields of proteins in readily isolatable forms.

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Baltimore, MD, United States of America

Ru Chih Huang