# US 9,040,505 B2 · Benzoquinone derivative E3330 in combination with chemotherapeutic agents for the treatment of cancer and angiogenesis > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 9,040,505 B2 - Document ID: US9040505B2 - Status: Granted - Kind: B2 - Application number: 12/679,824 - Filed: 2008-09-22 - Published: 2010-11-11 - Granted: 2015-05-26 - Earliest claimed: 2007-09-26 - Assignees: Indiana University Research and Technology Corporation - Applicants: Mark R. Kelley - Inventors: Mark R. Kelley - Web page: https://patentgrep.com/patent/US9040505B2 ## CPC - A61K 31/201: having one or two double bonds, e.g. oleic, linoleic acids - A61K 31/122: having the oxygen directly attached to a ring, e.g. quinones, vitamin K1, anthralin - A61K 31/13: Amines {(A61K31/04 takes precedence)} - A61K 31/195: having an amino group - A61K 31/198: Alpha-amino acids, e.g. alanine or edetic acid [EDTA] (betaine A61K31/205; proline A61K31/401; tryptophan A61K31/405; histidine A61K31/4172; peptides not degraded to individual amino acids A61K38/00) - A61K 31/203: Retinoic acids {; Salts thereof} - A61K 31/282: Platinum compounds - A61K 31/454: containing a five-membered ring with nitrogen as a ring hetero atom, e.g. pimozide, domperidone - A61K 31/7068: having oxo groups directly attached to the pyrimidine ring, e.g. cytidine, cytidylic acid - A61K 33/243: Platinum; Compounds thereof - A61K 39/3955: {against proteinaceous materials, e.g. enzymes, hormones, lymphokines} - A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca - A61P 27/02: Ophthalmic agents - A61P 35/00: Antineoplastic agents - A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D) - A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS ## Abstract Disclosed are novel methods for the therapeutic treatment of cancer and angiogenesis. The enzyme Ape1/Ref-1, via its redox function, enhances the DNA binding activity of transcription factors that are associated with the progression of cancer. The present invention describes the use of agents to selectively inhibit the redox function of Ape1/Ref-1 and thereby reduce tumor cell growth, survival, migration and metastasis. In addition, Ape1/Ref-1 inhibitory activity is shown to augment the therapeutic effects of other therapeutics and protect normal cells against toxicity. Further, Ape1/Ref-1 inhibition is shown to decrease angiogenesis, for use in the treatment of cancer as well other pathologic conditions of which altered angiogenesis is a component. ## Claims ### Claim 1 A method for inhibiting a physiological disorder associated with altered angiogenesis, the method comprising administering to a subject in need thereof an effective amount of 3-[(5-(2,3-dimethoxy-6-methyl 1,4-benzoquinoyl)]-2-nonyl-2-propenoic acid; a pharmaceutically acceptable salt or a pharmaceutically acceptable solvate thereof which selectively inhibits the redox function of Ape1/Ref-1, wherein the physiological disorder associated with altered angiogenesis is selected from the group consisting of diabetic retinopathy, degenerative maculopathy, retrolental fibroplasias, advanced macular degeneration and retinal angiomatous proliferation. ### Claim 2 (depends on 1) The method of claim 1 wherein said disorder is advanced macular degeneration. ### Claim 3 (depends on 2) The method of claim 2 wherein said advanced macular degeneration is age-related macular degeneration (AMD). ### Claim 4 (depends on 1) The method of claim 1 wherein at least one additional therapeutic agent is administered to said subject. ### Claim 5 (depends on 4) The method of claim 4 wherein said additional therapeutic agent is retinoic acid. ### Claim 6 (depends on 4) The method of claim 4 wherein said additional therapeutic agent is bevacizumab. ### Claim 7 A method for inhibiting pancreatic cancer or adult or pediatric gliomas associated with altered angiogenesis comprising administering to a subject in need thereof an effective amount of 3-[(5-(2,3-dimethoxy-6-methyl 1,4-benzoquinoyl)]-2-nonyl-2-propenoic acid; a pharmaceutically acceptable salt or a pharmaceutically acceptable solvate thereof which selectively inhibits the redox function of Ape1/Ref-1. ### Claim 8 (depends on 7) The method of claim 7, wherein at least one additional therapeutic agent selected from the group consisting of melphalan, gemcitabine, cisplatin, thalidomide and its derivatives, and retinoic acid is administered to said subject. ### Claim 9 A method for inhibiting pancreatic cancer associated with altered angiogenesis comprising administering to a subject in need thereof an effective amount of 3-[(5-(2,3-dimethoxy-6-methyl 1,4-benzoquinoyl)]-2-nonyl-2-propenoic acid; a pharmaceutically acceptable salt or a pharmaceutically acceptable solvate thereof which selectively inhibits the redox function of Ape1/Ref-1. ### Claim 10 (depends on 9) The method of claim 9 wherein at least one additional therapeutic agent is administered to said subject. ### Claim 11 (depends on 9) The method of claim 9 wherein said additional therapeutic agent is selected from the group consisting of melphalan, gemcitabine, cisplatin, thalidomide and its derivatives, and retinoic acid. ### Claim 12 A method for inhibiting pancreatic cancer or adult or pediatric gliomas comprising administering to a subject in need thereof an effective amount of 3-[(5-(2,3-dimethoxy-6-methyl 1,4-benzoquinoyl)]-2-nonyl-2-propenoic acid; a pharmaceutically acceptable salt or a pharmaceutically acceptable solvate thereof which selectively inhibits the redox function of Ape1/Ref-1 and inhibits tumor cell growth.