University of Louisville Research Foundation, Inc.

Advanced Cancer Therapeutics, LLC

Cornell University

University of Cape Town

Repairogen Corp.

Other

Antisoma Research Limited

John Olaf Trent

Paula J Bates

Donald Miller

Sucheta Telang

Jason Chesney

Pooran Chand

Gilles Hugues Tapolsky

Brian F Clem

Jason B Meier

Xiaohua Xu

Joseph A Burlison

Robert A Mitchell

Pengbo Zhou

Nagaraju Miriyala

Michael Henry Boice

Shin-je Ghim

A Bennett Jenson

Albert Cunningham

Virna Drucille Leaner

Pauline Janet Van Der Watt

Chenyi Yang

Frank Borchetta

Donald M Miller

Tongalp H Tezel

Henry J Kaplan

Chi Li

Geoffrey J Clark

Ben Frazier Taylor

Kelby B Napier

Daniel Callaghan

Jeffrey C Petruska

J Christopher States

Methods and pharmaceutical compositions are provided, which make use of compounds disclosed herein, including (I). The methods and compositions are useful for producing local or regional anesthesia or analgesia in nerve tissue of a subject.

Local and regional anesthesia and analgesia

Methods and pharmaceutical compositions for inhibiting 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 4 (PFKFB4) and the treatment of cancer are described.

Compounds for the treatment of cancer

Some embodiments of the invention include inventive compounds (e.g., compounds of Formula (I)). Other embodiments include compositions (e.g., pharmaceutical compositions) comprising the inventive compound. Still other embodiments of the invention include compositions (e.g., pharmaceutical compositions) for treating, for example, certain diseases using the inventive compounds. Some embodiments include methods of using the inventive compound (e.g., in compositions or in pharmaceutical compositions) for administering and treating (e.g., diseases such as cancer). Further embodiments include methods for making the inventive compounds. Additional embodiments of the invention are also discussed herein.

Compounds, compositions, methods for treating diseases, and methods for preparing compounds

Described are compositions containing quinones that show activity in enhance DNA repair and/or prevent damage to DNA and/or upregulate genes associated with wound healing. The quinones are thymoquinone, lapachol, myrtucommulone C, or mixtures thereof, and can be formulated into cosmetic compositions for topical administration to a subject in need thereof. The cosmetic compositions can also include sunscreens, surfactants, sunless tanning agents, desquamation agents, antiperspirants, colorants, preservatives and mixtures; and a cosmetically acceptable carrier. The compositions should find use in methods for treating the signs of ageing in mammals, dermatitis and wound healing via topical application to a site in need thereof, such as the skin or hair of the mammals or a wound site.

Cosmetic compositions containing quinones and their topical use on skin and hair

Some embodiments of the invention include inventive polypeptides (e.g., mutant VP2 proteins) and virus-like particles made from the inventive polypeptides. Other embodiments of the invention include compositions for treating (e.g., preventing) parvovirus (e.g., erythrovirus or parvovirus B19) infection and other diseases. Further embodiments include methods for administering compositions to an animal. Other embodiments include treating (e.g., preventing) parvovirus (e.g., erythrovirus or parvovirus B19) infection and other diseases. Still other embodiments include nucleic acid sequences that encode the inventive polypeptides. Additional embodiments of the invention are also discussed.

Compositions and methods for treating, including preventing, parvovirus infections and related diseases

Selective PFKFB4 inhibitors for the treatment of cancer

Some embodiments of this invention include methods for treating disease and methods for administering a compound of the invention. In some aspects of the invention, diseases can be treated by administration of compositions comprising a compound of the invention. Pharmaceutical compositions of some embodiments of the present invention comprise a compound of the invention.

Compounds for treating cancer, for administering, and for pharmaceutical compositions

Described are compositions containing quinones that show activity in enhance DNA repair and/or prevent damage to DNA. The quinones are thymoquinone, lapachol, myrtucommulone C, or mixtures thereof, and can be formulated into cosmetic compositions for topical administration to a subject in need thereof. The cosmetic compositions can also include sunscreens, surfactants, sunless tanning agents, desquamation agents, antiperspirants, colorants, preservatives and mixtures; and a cosmetically acceptable carrier. The compositions should find use in methods for treating the signs of ageing in mammals via topical application to the skin or hair of the mammals.

Some embodiments of the invention include inventive compounds. Other embodiments include compositions (e.g., pharmaceutical compositions) comprising the inventive compound. Still other embodiments of the invention include compositions (e.g., pharmaceutical compositions) for treating, for example, certain diseases using the compounds. Some embodiments include methods of using the inventive compound (e.g., in compositions or in pharmaceutical compositions) for administering and treating (e.g., diseases such as cancer). Further embodiments include methods for making the inventive compounds. Other embodiments include PFKFB4 inhibitors and methods of using the same that can target neoplastic cells, including, such as, mechanisms within those cells that relate to the use of the glycolytic pathway. In other embodiments, small molecule PFKFB4 inhibitors are used to disrupt the kinase domain of PFKFB4 and, in some instances, decrease the glucose metabolism and growth of human cancers. Additional embodiments of the invention are also discussed herein.

Inhibitors for the treatment of cancer and related methods

Implementations of the present invention include a compound and methods for inhibiting karyopherin beta 1 activity by administering to a patient in need thereof a therapeutically effective amount of a substituted benzoxazepine. The compound of Formula II, 9-[(1-methylpiperidin-3-yl)methoxy]-4-[(6-methylpyridin-2-yl)methyl]-7-(5-methylthiophen-2-yl)-3,5-dihydro-2H-1,4-benzoxazepine or one of its salts, inhibits the import of protein and transcription factors, such as NFAT and P65/NFKB into the nucleus of a cell, and thus has anti-cancer effects enabling the compound to be used for cancer treatment. 

Substituted benzoxazepine for cancer therapy

Compounds, including quinoxaline derivatives of formula I, for use in the treatment of cancer are described. In general, the compounds inhibit the import of proteins and transcription factors such as Kpn&#x3b1;, AP-1, P65, NFAT into the nucleus of a cell by inhibiting the nuclear import protein, Kpn&#x3b2;1. Cancer cells have elevated levels of Kpn&#x3b2;1 and the inhibition of their nuclear import activity induces cell apoptosis. The administration of an effective amount of any one of the compounds results in cell apoptosis in cancer cells, while non-cancer cells are substantially unaffected by the inhibition of Kpn&#x3b2;1's nuclear import activity. 

Substituted pyrrolo[2,3-b]quinoxalines for cancer therapy

The pro-apoptotic Bcl-2 protein Bax initiates apoptosis in almost all apoptotic paradigms. Agents facilitating disruptive Bax insertion into mitochondrial membranes have potential as cancer therapeutics. Small molecule compounds associating with the hydrophobic groove of the pro-apoptotic Bcl-2 protein Bax have been identified and found to promote Bax-dependent, but not Bak-dependent, apoptosis. The compounds alter Bax protein stability in vitro and promote Bax insertion into mitochondria, leading to Bax-dependent mitochondrial outer membrane permeabilization and apoptosis. The compounds activating the pro-apoptotic Bcl-2 protein Bax inhibit the growth of tumors by inducing apoptosis. Pharmaceutical compositions comprising the compounds that activate Bax and induce Bax-dependent apoptosis are useful as anti-cancer therapeutic agents alone or with other anti-cancer agents. Methods for inducing apoptosis and for treating cancer involve administering the compounds to a patient in need thereof.

BAX-activating cancer therapeutics

Small molecule inhibitors of 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3) having the following formula: Formula (1) are provided herein. Also provided herein are pharmaceutical compositions containing Formula I compounds, together with methods of treating cancer, methods of inhibiting PFK.FB3 enzymatic activity, methods of inhibiting glycolytic flux, and methods of treating tumors by administering an effective amount of a Formula I compound. 

Small molecule inhibitors of PFKFB3 and glycolytic flux and their methods of use as anti-cancer therapeutics

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Louisville, KY, United States of America

John Olaf Trent