Arqule, Inc.

Boston Biomedical, Inc.

Zhoushan Haizhongzhou Xinsheng Pharmaceuticals Co., Ltd.

Sumitomo Dainippon Pharma Oncology, Inc.

Cyclis Pharmaceuticals, Inc.

Zhiwei Jiang

Chiang Jia Li

Wei Li

David Leggett

Youzhi Li

Harry Rogoff

Jifeng Liu

Xian Li

Aijin Wang

Dasharatha G Reddy

Hongwei Hu

Jiali Xu

Yuesong Hu

Yan Ye

Mark Anthony Ashwell

Jean-Marc Lapierre

Manish Tandon

Yanbin Liu

Jie Wang

Qinglong Li

Qingrong Li

Jane Hogeland

The present invention relates to a novel naphtho class of compounds as Stat3 pathway inhibitors and as cancer stem cell inhibitors; to methods of using such compounds to treat cancer; to methods of using such compounds to treat disorders in a mammal related to aberrent Stat3 pathway activity; to pharmaceutical compositions containing such compounds.

Stat3 pathway inhibitors and cancer stem cell inhibitors

The present invention discloses esters of 4,9-dihydroxy-naphtho[2,3-b]furans and methods of making and using the same. The present invention also discloses conversion of the esters into therapeutically active 4,9-dihydroxy-naphtho[2,3-b]furans in vivo. The present invention furthermore discloses pharmaceutical compositions comprising the esters of 4,9-dihydroxy-naphtho[2,3-b]furans for the treatment of various indications including proliferative diseases.

Esters of 4, 9-dihydroxy-naphtho [2, 3-b] furans for disease therapies

The present invention relates to a novel naphtho class of compounds as Stat3 pathway inhibitors and as cancer stem cell inhibitors; to methods of using such compounds to treat cancer; to methods of using such compounds to treat disorders in a mammal related to aberrant Stat3 pathway activity; to pharmaceutical compositions containing such compounds.

The present invention discloses novel naphtho[2,3-b]furan-4,9-diones and naphtho[2,3-b]thiophene-4,9-diones and methods of making and using the same. The present invention also discloses pharmaceutical compositions comprising novel naphtho[2,3-b]furan-4,9-dione or naphtho[2,3-b]thiophene-4,9-diones for the treatment of various indications including proliferative diseases.

Naphthoquinones for disease therapies

The present invention relates to polymer-modified quinone-containing and carbonyl-containing therapeutic agents, including polymer-modified &#x3b2;-lapachone compounds, and methods of treating cancer by administering the polymer-modified therapeutic agents to a subject. Polymer-modification of therapeutic agents, such as &#x3b2;-lapachone compounds, provides effective transport of polymer-modified therapeutic agents to tumor cells or tumor tissues by exploiting the EPR effect in tumor tissues.

Pharmaceutical compositions of &#x3b2;-lapachone and &#x3b2;-lapachone analogs with improved tumor targeting potential

Beta-lapachone, which is poorly soluble in most pharmaceutically acceptable solvents, has demonstrated significant antineoplastic activity against human cancer lines. The present invention overcomes this significant limitation by teaching novel pharmaceutical compositions comprising a therapeutically effective amount of Beta-lapachone, or a derivative or analog thereof, and a pharmaceutically acceptable solubilizing carrier molecule, which may be at water-solubilizing carrier molecule such as hydroxypropyl-&#x3b2;-cyclodextrin, or an oil-based solubilizing carrier molecule, for enhancing the solubility of Beta-lapachone in aqueous solution. The therapeutically effective amount of Beta-lapachone, or a derivative or analog thereof, may be complexed with the pharmaceutically acceptable solubilizing carrier molecule in aqueous solution. The novel pharmaceutical compositions may be administered with a second anticancer agent or in combination with radiation therapy. A formulation of Beta-lapachone or a derivative or analog thereof, complexed with a pharmaceutically acceptable solubilizing carrier molecule, wherein the complex can be freeze-dried and when subsequently reconstituted in aqueous solution is substantially soluble is also disclosed. Emulsions of Beta-Lapachone in a pharmaceutically acceptable fat emulsion vehicle are also provided. Also disclosed are methods for treating cancer by administering to a patient the novel pharmaceutical compositions and formulations. Pharmaceutical kits are also provided.

Pharmaceutical compositions containing beta-lapachone, or derivatives or analogs thereof, and methods of using same

A novel process for synthesizing &bgr;-lapachone (beta-lapachone), an agent that has demonstrated significant antineoplastic activity against human cancer lines. The process comprises the conversion of starting material, 2-hydroxy-1,4-naphothoquinone into &bgr;-lapachone intermediate, lapachol. The lapachol is then converted to &bgr;-lapachone by treatment with sulfuric acid and purified by recrystallization from ethanol. This novel process is extremely simple and provides &bgr;-lapachone in excellent quality and high yield.

Synthesis of &bgr;-lapachone and its intermediates

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Stow, MA, United States of America

Zhiwei Jiang