Abstract: A novel compound, (E)-1-(pyridyn-4-yl)-3-(7-(trifluoromethyl)quinolin-2-yl)-prop-2-en-1-one, is provided herein. (E)-1-(pyridyn-4-yl)-3-(7-(trifluoromethyl)quinolin-2-yl)-prop-2-en-1-one is an inhibitor of 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3) with surprisingly superior efficacy and pharmacodynamic properties in vitro and in vivo. Also provided are pharmaceutical compositions including the compound and methods of use of the compound in treating cancer and tumors in vivo, as well as inhibiting glycolytic flux and PFKFB3 enzymatic activity in cells.
Abstract: Oligonucleotides according to the following Formula I are provided herein: 5?-Xa-Q-Yb-3? wherein X and Y are each independently selected from the group consisting of a lipid and a polyethylene glycol; Q is a quadruplex-forming guanine-rich promoter gene oligonucleotide (GPGO); a is 0 or 1; and b is 0 or 1, wherein the sum of a+b=1 or 2. Also provided are compositions including Formula I oligonucleotides and methods of their use in inhibiting cell growth, treating cancer, and treating tumors.
Abstract: 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.
Type:
Grant
Filed:
February 22, 2011
Date of Patent:
August 2, 2016
Assignees:
Advanced Cancer Therapeutics, LLC, University of Louisville Research Foundation, Inc.
Inventors:
Pooran Chand, Jason A. Chesney, Brian F. Clem, Gilles H. Tapolsky, Sucheta Telang, John O. Trent
Abstract: Compounds useful for the inhibition of macrophage migration inhibitory factor (MIF) are provided herein, having the Formula I: wherein A is selected from the group consisting of aromatic or non-aromatic rings, bicyclic rings, polycyclic rings, alkenes or alkynes; B is H, OH, OR, SR, NH2, NHR, or alkyl; R is H or alkyl, and X and Y are independently N or CH, but one of X and Y must be N. Also provided are pharmaceutical compositions that contain a Formula I compound and methods for the treatment of MIF-implicated diseases or conditions that include administering a safe and effective amount of a Formula I compound.
Type:
Application
Filed:
July 20, 2015
Publication date:
December 24, 2015
Applicants:
ADVANCED CANCER THERAPEUTICS, LLC, UNIVERSITY OF LOUISVILLE RESEARCH FOUNDATION, INC.
Inventors:
Robert A. Mitchell, John O. Trent, Pooran Chand, Gilles Hugues Tapolsky
Abstract: Compounds useful for the inhibition of macrophage migration inhibitory factor (MIF) are provided herein, having the Formula (I): wherein A is selected from the group consisting of aromatic or non-aromatic rings, bicyclic rings, polycyclic rings, alkenes or alkynes; B is H, OH, OR, SR, NH2, NHR, or alkyl; R is H or alkyl, and X and Y are independently N or CH, but one of X and Y must be N. Also provided are pharmaceutical compositions comprising a Formula I compound and methods for the treatment of MIF-implicated diseases or conditions, comprising administering a safe and effective amount of a Formula I compound.
Type:
Grant
Filed:
September 24, 2010
Date of Patent:
October 20, 2015
Assignees:
University of Louisville Research Foundation, Inc., Advanced Cancer Therapeutics, LLC
Inventors:
Robert A. Mitchell, John O. Trent, Pooran Chand, Gilles Hugues Tapolsky
Abstract: The present invention provides a method for inhibiting the proliferation of malignant and/or hyperplastic cells in a subject by administering to the subject a therapeutically effective amount of a guanosine rich oligonucleotide. The present invention also provides oligonucleotides which are capable of being specifically bound to a specific cellular protein which is nucleolin and/or nucleolin in nature, which is implicated in the proliferation of cells, specifically malignant and/or hyperplastic cells, and a method for their selection.
Type:
Grant
Filed:
October 29, 2004
Date of Patent:
February 11, 2014
Assignee:
Advanced Cancer Therapeutics, LLC
Inventors:
Donald M. Miller, Paula J. Bates, John O. Trent
Abstract: A methods and compounds for inhibiting 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3) are described. Also described are methods of inhibiting cell proliferation, treating cancer, and screening compounds to determine their ability to inhibit PFKFB3.
Type:
Grant
Filed:
November 30, 2011
Date of Patent:
October 15, 2013
Assignees:
Advanced Cancer Therapeutics, LLC, University of Louisville Research Foundation, Inc.
Inventors:
Gilles Tapolsky, Pooran Chand, John O. Trent, Sucheta Telang, Brian F. Clem, Jason A. Chesney
Abstract: 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.
Type:
Application
Filed:
February 22, 2011
Publication date:
March 7, 2013
Applicants:
UNIVERSITY OF LOUISVILLE RESEARCH FOUNDATION, INC., ADVANCED CANCER THERAPEUTICS, LLC
Inventors:
Pooran Chand, Jason A. Chesney, Brian F. Clem, Gilles H. Tapolsky, Sucheta Telang, John O. Trent
Abstract: A methods and compounds for inhibiting 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3) are described. Also described are methods of inhibiting cell proliferation, treating cancer, and screening compounds to determine their ability to inhibit PFKFB3.
Type:
Application
Filed:
November 30, 2011
Publication date:
July 12, 2012
Applicants:
UNIVERSITY OF LOUISVILLE RESEARCH FOUNDATION, INC., ADVANCED CANCER THERAPEUTICS, LLC
Inventors:
Gilles Tapolsky, Pooran Chand, John O. Trent, Sucheta Telang, Brian F. Clem, Jason A. Chesney
Abstract: Compositions and methods for modulating tumor proliferation in an individual are provided. The methods employ nucleolin-binding agents, such as aptamers. The aptamers of the present invention can be used to modulate the proliferation of malignant, dysplastic, hyperproliferative, and/or metastatic cells through interference with molecular interactions and functions of nucleolin in the tumor cell.
Type:
Grant
Filed:
October 31, 2007
Date of Patent:
February 14, 2012
Assignee:
Advanced Cancer Therapeutics, LLC
Inventors:
John O. Trent, Paula J. Bates, Donald J. Miller
Abstract: Small molecule choline kinase inhibitors having the following formula: are provided herein. Also provided herein are pharmaceutical compositions containing Formula I compounds, together with methods of treating cancer, methods of inhibiting choline kinase enzymatic activity, and methods of treating tumors by administering an effective amount of a Formula I compound.
Type:
Application
Filed:
December 22, 2010
Publication date:
October 20, 2011
Applicants:
ADVANCED CANCER THERAPEUTICS, LLC, UNIVERSITY OF LOUISVILLE RESEARCH FOUNDATION, INC.
Inventors:
Pooran Chand, Jason A. Chesney, Brian F. Clem, Gilles H. Tapolsky, Sucheta Telang, John O. Trent
Abstract: Compositions and methods for modulating tumor proliferation in an individual are provided. The methods employ nucleolin-binding agents, such as aptamers. The aptamers of the present invention can be used to modulate the proliferation of malignant, dysplastic, hyperproliferative, and/or metastatic cells through interference with molecular interactions and functions of nucleolin in the tumor cell.
Type:
Grant
Filed:
October 31, 2007
Date of Patent:
June 14, 2011
Assignee:
Advanced Cancer Therapeutics, LLC
Inventors:
John O. Trent, Paula J. Bates, Donald M. Miller