Johns Hopkins University

Erimos Pharmaceuticals, LLC

University System of Maryland

National Yang Ming Chiao Tung University

Academia Sinica

Ru Chih C Huang

Jonathan Daniel Heller

Jih Ru Hwu

Chih-Chuan Chang

John N Gnabre

David Mold

Ming-Hua Hsu

Kotohiko Kimura

Apostolos Gittis

Julie A Dohm

Ibrahim S Abd-Elazem

Evangelos Moudrianakis

Neil Frazer

Yu-Ling Lin

Hong Yu Chen

Kuang-Wen Liao

Rocio Alejandra Lopez

Melissa Rhodes

Yu-Chuan Liang

Paul Edward Giza

Jong Ho Chun

Chien-Hsien Lai

Richard Dalby

Niharika Khanna

Richard Park

Elaine Lin

Ming Hua Hsu

Ibrahim Shawky Abd Elazem

Ko Yung King

Szu Chun Wu

Ke Yung King

Tiffany Jackson

Kunag-Wen Liao

Jonathan D Heller

The present invention provides novel pharmaceutical formulations comprising derivatives of NDGA, including MN (tetra-0-methyl nordihydroguaiaretic acid) and temozolomide and their use in the inhibition and treatment of neoplastic diseases, including glioblastoma multiforme, lung and other cancers.

Formulations of terameprocol and temozolomide and their use in stimulation of humoral immunity in tumors

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 provides expression vectors useful for high-throughput screening of gene libraries. In a specific embodiment, an expression vector comprising (a) the Rop gene operatively linked to the trp promoter-operator; (b) a purification tag sequence and a protease cleavage site downstream of the Rop gene; and (d) a multiple cloning site downstream of the protease cleavage site, wherein the insertion of a heterologous gene of interest into the multiple cloning site and subsequent expression thereof in a host cell produces a high yield of a fusion protein comprising the Rop protein and the protein encoded by the heterologous gene of interest without the need of chemical inducers, temperature shifts, or growth medium alterations to initiate protein synthesis, and wherein the fusion protein controls plasmid replication at temperatures below about 30&#xb0; C. but exhibits runaway plasmid replication when cultured at about 37&#xb0; C.

Bacterial expression plasmid

Compounds, compositions and methods for the treatment of HIV/HSP/HPV, in particular, compositions and methods for a 3 part combination therapy for HIV/HSV/HPV, comprising a viral attachment inhibitor, a viral sequence integration inhibitor, and a proviral transcription inhibitor. The therapy is advantageous for the treatment of HIV infection, and is also effective for HSV and HPV infection. Also disclosed are novel viral attachment inhibitors and methods of use.

Synergistic antiviral compositions comprising a viral attachment inhibitor, an integration inhibitor, and a proviral transcription inhibitor, and their use

Disclosed is a composition comprising a derivative of NDGA and 7-hydroxystaurosporine. The composition can be in a unit dose form or kit. 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 7-hydroxystaurosporine

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.

Conjugates of nitroimidazoles and their use as chemotherapeutic agents

Synergistic antiviral compositions comprising a viral attachment inhibitor, integration inhibitor, and proviral transcription inhibitor

The present invention provides for compositions, kits and methods for treatment of intraepithelial neoplasia, where the compositions include catecholic butanes, which include NDGA derivatives.

Methods and compositions for treatment of intraepithelial neoplasia

Reaction of nordihydroguaiaretic acid with various alkyl chlorides, 1-piperidinecarbonyl chloride, methyl chloroformate, or 1,1'-carbonyldiimidazole under alkaline conditions produced the corresponding phenol ethers, carbamates and carbonates, respectively, in 67-83% yields (Scheme 1 and Scheme 2). Among these derivatives, the nitrogen-containing compounds were converted to the corresponding hydrochloride salts. Having good solubility, these NDGA derivatives were found to be stable in aqueous solution. These new compounds exerted potent activities against HIV Tat-regulated transactivation in cos-7 cells. The most active transcription inhibitor compound of this series 5b (PN, Tetrapiperidino NDGA, meso-2,3-dimethyl-1,4-bis(3,4-[2-(piperidino)ethoxypehnyl])butane tetrakishydrochloride salt) has an ICof 0.88 &#x3bc;

Heterocyclic and carbonate derivatives of NDGA and their use as new anti-HIV and anti-cancer agents

Use of nordihydroguaiaretic derivatives to suppress CDC-2 and survivin, stimulate apoptosis, and treat tumors.

Method for treatment of tumors using nordihydroguaiaretic acid derivatives

Reaction of nordihydroguaiaretic acid with various alkyl chlorides, 1-piperidinecarbonyl chloride, methyl chloroformate, or 1,1'-carbonyldiimidazole under alkaline conditions produced the corresponding phenol ethers, carbamates and carbonates, respectively, in 67-83% yields (Scheme 1 and Scheme 2). Among these derivatives, the nitrogen-containing compounds were converted to the corresponding hydrochloride salts. Having good solubility, these NDGA derivatives were found to be stable in aqueous solution. These new compounds exerted potent activities against HIV Tat-regulated transactivation in cos-7 cells. The most active transcription inhibitor compound of this series 5b (PN, Tetrapiperidino NDGA, meso-2,3-dimethyl-1,4-bis(3,4-[2-(piperidino)ethoxyphenyl])butane tetrakishydrochloride salt) has an ICof 0.88 &#x3bc;

The present invention provides kits, methods and compositions for the treatment of tumor and other proliferative diseases such as tumors. The compositions herein contain a substantially pure preparation of at least one catecholic butane, including, for example, NDGA compounds in a pharmaceutically acceptable carrier or excipient. The catecholic butane such as NDGA or its derivatives are administered to one or more subjects in need of treatment by a route other than direct injection into the affected tissues or topical application on affected tissues.

Methods for delivery of catecholic butanes for treatment of tumors

A method for suppressing undesired viral growth in a host which comprises administering to the host an effective amount of a compound of the formula:wherein R, R, Rand Rare independently selected from the group consisting of HO&#x2014;, CHO&#x2014; and CH(C&#x2550;O) O&#x2014;. The method is exemplified by inhibiting Tat transactivation of a lentivirus and in suppressing Herpes simplex virus.

Method for the suppression of viral growth

Purified antiviral compounds, pharmaceutical formulations containing the compounds, and methods of use of the compounds are provided. The compositions of the invention are isolated antiviral components from plant extracts derived from, for example,, that find use in the treatment of viral infections, such as by inhibiting the activity of viral integrase. Methods for isolation and purification of the antiviral compounds are additionally provided.

Antiviral compositions and methods of use

Nordihydroguaiaretic acid derivatives and methods of use thereof for the treatment of tumors.

Growing community of inventors

Baltimore, MD, United States of America

Ru Chih C Huang