Virginia Commonwealth University

Center for Innovative Technology

Allos Therapeutics, Inc.

Other

Xechem International, Inc.

The Center of Innovative Technology

Donald J Abraham

Ramnarayan Randad

Gajanan S Joshi

Richmond E Danso-Danquah

Martin K Safo

Ahmed Mehanna

Michael J Gerber

Stephen J Hoffman

Mona Mahran

Jayashree Panikker

James C Burnett

Telih Boyiri

Melissa Grella

Amal Yousseff

Sanjeev Kulkarni

Louis Selig Harris

Claude Poyart

Hsiang-Ru Lin

Changquing Wang

Jim Christian Burnett

Paul S Swerdlow

B J Meade

Samuel Nokuri

Graham A Patrick

Albert E Munson

Faik N Musayev

Changging Wang

Compounds for the treatment of estrogen-receptor related maladies are provided. Compounds with anti-androgenic properties also are provided. In particular, the invention provides compounds that are tetrahydroquinoline phenylamide derivatives and are useful for the treatment of breast and prostate cancer, and osteoporosis.

Compounds having antiestrogenic and tissue selective estrogenic properties, and compounds with anti-androgenic properties for treatment of prostate cancer and androgen receptor dependent diseases

The provides compounds for the treatment of sickle-cell disease. In particular, the invention provides 5-membered heterocyclic anti-sickling agents that are highly effective and non-toxic, and methods for their use. The compounds include analogues and derivatives of naturally occurring occurring 5-hydroxymethyl-2-furfuraldehyde, 5-Ethyl-2-furfuraldehyde, 5-Methyl-2-furfuraldehyde, and 2-furfuraldehyde, and prodrug forms of the compound.

Anti-sickling agents

Compounds for the treatment of sickle-cell disease, and methods for their use are provided. The compounds have a dual mode of action. First, binding of the compounds to hemoglobin increases the oxygen affinity of both normal and sickle hemoglobin. Secondly, binding of these compounds to the N-terminal amino acid of sickle hemoglobin results in destabilization of potential contacts between sickle hemoglobin molecules, preventing polymerization and the formation of fibrous precipitates of the sickle hemoglobin. The compounds are also useful for inducing hypoxia, e.g. to augment cancer treatments.

A family of substituted chiral allosteric effectors of hemoglobin is useful for delivering more oxygen to hypoxic and ischemic tissues by reducing the oxygen affinity of hemoglobin in whole blood.

Substituted chiral allosteric hemoglobin modifiers

Chemical structures have been identified which allosterically modify pyrvate kinase and inhibit enzymatic activity. These compounds can be used as pharmaceuticals in the treatment of a wide variety of diseases and disorders where influencing metabolic processes is beneficial, such as the glycolytic pathway, all pathways which use ATP as an energy source, and all pathways which involve 2,3-diphosphoglycerate related to the delivery of oxygen by modifying hemoglobin's oxygen affinity, treatments of tumor and cancer and Alzheimer's disease (AD).

Allosteric inhibitors of pyruvate kinase

Chemical structures have been identified which allosterically modify pyrvate kinase and either inhibit or activate enzymatic activity. These compounds can be used as pharmaceuticals in the treatment of a wide variety of diseases and disorders where influencing metabolic processes is beneficial, such as the glycolytic pathway, all pathways which use ATP as an energy source, and all pathways which involve 2,3-diphosphoglycerate.

A family of compounds has been found to be useful for right-shifting hemoglobin towards a low oxygen affinity state. The effect has particular application in a wide variety of treatments including hypoxia, hypothermia, ischemia, stroke, ARDS, COPD, surgical blood loss, acute nonvolemic hemodilutions, wounds, diabetic ulcers, chronic leg ulcers, pressure sores, tissue transplants, and sepsis. The compounds are capable of acting on hemoglobin in whole blood.

Allosteric modifiers of hemoglobin

A family of compounds has been found to be useful for right-shifting hemoglobin towards a low oxygen affinity state. The compounds are capable of acting on hemoglobin in whole blood. In addition, the compounds can maintain the oxygen affinity in blood during storage and can restore the oxygen affinity of outdated blood.

A method of using allosteric hemoglobin modifier compounds which promote the release of oxygen to improve delivery of oxygen from the mother to the fetus and the release of oxygen to tissues from fetal hemoglobin in treatment of maternal and fetal related syndromes.

Perinatal treatment of a fetus to avoid oxygen deprivation

Allosteric modifiers of hemoglobin useful for decreasing oxygen affinity

A family of compounds has been found to be useful for right-shifting hemoglobin towards a low oxygen affinity state. The effect has particular application in radiation oncology applications. The compounds are capable of acting on hemoglobin in whole blood.

Use of allosteric hemoglobin modifiers in combination with radiation

Medical uses of allosteric hemoglobin modifier compounds in patient care

Various hydroxy benzaldehyde derivatives including Vanillin, a natural product derived from the vanilla bean that is commonly used as a flavoring agent, is administered by injection (i.v., i.m., s.c., and the like) or intravenous infusion in an effective dose amount to a patient in need of calming or sedation.

Method of calming or sedating an animal with a hydroxy benzaldehyde

Drug compounds are used as allosteric modifiers of hemoglobin present in red blood cells. The compounds bind to only a single pair of symmetry related sites in the central water cavity of hemoglobin at the Lys 99.alpha., Arg 141.alpha., and Asn 108 .beta. residues. When one of the drug compounds is bound to hemoglobin, it will join three separate sub-units of the hemoglobin molecule and stabilize the hemoglobin in a lower oxygen affinity state. Because the compounds used in this method are either not bound by serum albumin or only interact to small degrees with serum albumin, the compounds are active in whole blood and in vivo. The process of allosterically modifying hemoglobin towards a low oxygen affinity state in whole blood and in vivo could be used in a wide variety of applications including in treatments for ischemia, heart disease, wound healing, Alzheimer's, depression, schizophrenia, adult respiratory distress syndrome (ARDS), etc., in extending the shelf-life of blood or restoring the oxygen carrying capacity of out-dated blood, and as sensitizers for x-ray irradiation in cancer therapy, as well as in many other applications.

Growing community of inventors

Midlothian, VA, United States of America

Donald J Abraham