Indiana University

Advanced Research & Technology Institute

Other

Apexian Pharmaceuticals, Inc.

Apex Therapeutics, Inc.

Purdue Research Foundation

Mark R Kelley

Melissa L Fishel

James Howard Wikel

David A Williams

John Eble

Richard F Borch

Timothy William Corson

Jill Fehrenbacher

Michael R Vasko

Angelo A Cardoso

Rodney L Nyland, Ii

John Duquid

Ronald P Mackwood

John M Broderick

John Duguid

Melissa Fishel

Rodney L Ii Nyland

Combination therapies including a Apurinic/Apyrimidinic Endonuclease/reduction-oxidation (redox) Factor-1 (APE1/Ref-1) inhibitor specific to inhibit the redox function of APE1/Ref-1 are disclosed herein. The Combination therapies can be used for treating various cancers, as well as other angiogenesis-mediated diseases (e.g., retinal diseases, cardiovascular diseases).

Use of APE1/Ref-1 inhibitors for treatment of retinal diseases

[[(2E)-2-[(3-methoxy-1,4-dioxo-1,4-dihydronaphthalen-2-yl)methylidene]-N,N-diethylpentanamide] (APX2009) and (2E)-2-[(3-methoxy-1,4-dioxo-1,4-dihydronapthalen-2-yl)methylidene]-N-methoxypentanamide] (APX2014) for inhibiting ocular diseases are disclosed herein.

Targeting ocular diseases with novel APE1/Ref-1 inhibitors

Methods of reducing neuronal sensitivity, thereby reducing inflammation and chronic pain, in subjects having diabetes are disclosed herein. Particularly disclosed are methods of administrating the apurinic/apyrimidinic endonuclease 1 redox factor 1 (APE 1/Ref-1) inhibitor, APX3330, to enhance the DNA base excision repair (BER) pathway, thereby reducing neuronal sensitivity to inflammatory mediators and alleviating inflammatory or chronic pain.

Prevention and reversal of inflammation induced DNA damage

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 disclosure 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.

Benzoquinone derivative E3330 in combination with chemotherapeutic agents for the treatment of bladder cancer

Compounds, compositions, and formulations, and accompanying methods useful for treating disorders arising from oxidative DNA damage, including oxidative DNA damage resulting from ionizing radiation or other therapy are described herein.

Compounds, compositions and methods for treating oxidative DNA damage disorders

Methods for targeting apurinic/apyrimidinic endonuclease1/redox effector factor 1 (APE1/Ref-1) are disclosed. More particularly, methods for inhibiting APE1/Ref-1 and hypoxia-mediated signaling for decreasing survival and invasion of tumor cells exposed to hypoxic conditions are disclosed.

Methods of targeting APE/Ref-1 to inhibit hypoxia signaling genes

The invention described herein pertains to compounds and compositions for treating Ape1 mediated diseases. In particular, the invention described herein pertains to quinone compounds and pharmaceutical compositions containing them for treating Ape1 mediated diseases.

Quinone compounds for treating APE1 mediated diseases

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.

Benzoquinone derivative E3330 in combination with chemotherapeutic agents for the treatment of cancer and angiogenesis

The invention described herein pertains to compounds and compositions for treating Ape1 mediated diseases. In particular, the invention described herein pertains to quinone compounds and pharmaceutical compositions containing them for treating mediated diseases.

Quinone compounds for treating Ape1 mediated diseases

Compounds, and methods and uses of compounds, and pharmaceutical compositions thereof, are described herein for treating leukemia. In particular, compounds, and methods and uses of compounds, and pharmaceutical compositions thereof, are described herein for treating acute lymphoblastic leukemia (ALL) in its various forms.

Compounds and methods for treating leukemia

This application describes quinone derivatives which target the redox site of Ape1/Ref1. Also included in the invention are pharmaceutical formulations containing the derivatives and therapeutic uses of the derivatives.

Quinone derivatives, pharmaceutical compositions, and uses thereof

Disclosed are methods and compositions for identifying, monitoring and treating premalignant and malignant conditions in a human subject. The present invention further discloses methods and compositions for determining cells undergoing apoptosis, and for increasing the efficacy of a cancer therapy. The methods involve the use of apurinic/apyrimidinic endonuclease (APE), independently, as a marker for (pre)malignant conditions and for apoptosis. Also described are polyclonal antibody preparations for use in methods for detecting APE and methods for modulating expression susceptibility of cells to apoptosis.

Growing community of inventors

Zionsville, IN, United States of America

Mark R Kelley