Abstract: The present invention provides novel pharmaceutical formulations comprising derivatives of NDGA, including M4N (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.

Abstract: In accordance with the present invention, the immunoregulatory activity of low doses of P4N was investigated. Unlike previously described antitumor drugs, low dose P4N, in doses of about 1 to 10 mg/kg, or at concentrations of about 10 to 100 nM, was surprisingly found to contribute to humoral immunity by raising the titers and activities of autoantibodies against GRP78 and F1F0 ATP synthase on the surface of CT26 cells, and inducing B cell proliferation and differentiation of plasma cells. Methods for inducing B cell proliferation, inducing BAFF stimulated B cell proliferation, and suppressing or inhibition growth of a neoplasia are provided.

Abstract: In accordance with the present invention, the immunoregulatory activity of low doses of P4N was investigated. Unlike previously described antitumor drugs, low dose P4N, in doses of about 1 to 10 mg/kg, or at concentrations of about 10 to 100 nM, was surprisingly found to contribute to humoral immunity by raising the titers and activities of autoantibodies against GRP78 and F1F0 ATP synthase on the surface of CT26 cells, and inducing B cell proliferation and differentiation of plasma cells. Methods for inducing endogenous antitumor autoantibodies (EAA) in a subject having a neoplasia comprising administering to the subject an effective amount of the nordihydroguaiaretic acid (NDGA) derivative P4N, or salts, solvates and stereoisomers thereof, as well as methods for inducing B cell proliferation, inducing BAFF stimulated B cell proliferation, and suppressing or inhibition growth of a neoplasia are also provided.

Abstract: 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° C. but exhibits runaway plasmid replication when cultured at about 37° C.

Abstract: 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.

Abstract: 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.

Abstract: 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.

Abstract: 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.

Abstract: 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.

Abstract: 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.

Abstract: 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° C. but exhibits runaway plasmid replication when cultured at about 37° C.

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

Abstract: 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 (P4N, Tetrapiperidino NDGA, meso-2,3-dimethyl-1,4-bis(3,4-[2-(piperidino)ethoxypehnyl])butane tetrakishydrochloride salt) has an IC50 of 0.88 ?M.

Abstract: 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.

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

Abstract: The present invention provides kits, methods and compositions for the treatment of diseases such as cancers. 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.

Abstract: 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.

Abstract: 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 (P4N, Tetrapiperidino NDGA, meso-2,3-dimethyl-1,4-bis(3,4-[2-(piperidino)ethoxyphenyl])butane tetrakishydrochloride salt) has an IC50 of 0.88 ?M.

Abstract: 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.

Abstract: 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.