The United States of America, As Represented by the Secretary, Department of Health and Human Services

University of California

Medtronic Vascular, Inc.

The University of Arizona

The United States of America

Leidos Biomedical Research, Inc.

Joseph Saavedra

Larry K Keefer

Anna E Maciag

Marc Hendriks

Peiwen Cheng

Robert L Cafferata

Eugene Tedeschi

Anthony L Fitzhugh

Vandana Kumari

Adam Renslo

David A Wink

Xinhua Ji

Peter P Roller

Frank McCormick

Katrina M Miranda

Miki Akamatsu

David J Waterhouse

David Turner

Debashree Basudhar

Marcin Dyba

Debra J Salmon

Daniela Andrei

Xia Xu

Regina G Ziegler

Elizabeth D Vo

Michel I P M Verhoeven

Lucy M Anderson

Michel L P M Verhoeven

Harinath Chakrapani

Provided herein are the K-Ras inhibitors of the formulae: Also provided are compositions comprising thereof for treating cancer.

K-Ras modulators

Disclosed is a method of treating cancer in a patient comprising administering to the patient an effective amount of a diazeniumdiolated (NO-containing) compound or a pharmaceutically acceptable salt thereof, wherein the cancer cell has an elevated level of reactive oxygen species (ROS) and/or a decreased level of one or more of PRX1, PRX6, and OGG1, compared to a normal cell of the same tissue or tissue type. An example of a diazeniumdiolated compound is Formula (I), wherein X and Q are defined herein. Also disclosed are diazeniumdiolated compounds, pharmaceutical compositions, and methods of use including enhancing the chemotherapeutic treatment of chemotherapeutic agents and high energy radiation. 

Diazeniumdiolated compounds, pharmaceutical compositions, and method of treating cancer

Disclosed are hybrid compounds that release both nitric oxide and a moiety that inhibits poly (ADP-ribose) polymerase (PARP), e.g., a compound or a pharmaceutically acceptable salt thereof of formula (I), wherein Rand m-p are as described herein. Also disclosed are pharmaceutical compositions and methods of use including treating cancer and enhancing the chemotherapeutic treatment of chemotherapeutic agents and high energy radiation. 

Hybrid diazeniumdiolated compounds, pharmaceutical compositions, and method of treating cancer

Disclosed is a compound of the formula (I) or a pharmaceutically acceptable salt thereof: (I) in which R, R, R, and Rare defined herein and pharmaceutical compositions thereof. Further provided is a method of treating various disorders, such as a disorder selected from the group consisting of a cardiovascular disorder, cancer, chronic pain, alcohol dependence, and inflammation in a patient comprising administering an effective amount of a compound or pharmaceutically acceptable salt of formula (I). 

Nitroxyl (HNO) releasing compounds and uses thereof in treating diseases

Methods for enhancing detection by mass spectroscopy (MS) and/or chromatographic separability of carbonyl-containing compounds such as steroids are disclosed. Reaction of a carbonyl compound with a sulfonhydrazide compound provides a sulfonhydrazone with enhanced ionization efficiency during the electrospray ionization process. In a particularly disclosed embodiment, derivatization of catechol estrogens with p-toluenesulfonhydrazide enhances both detection by atmospheric pressure ionization-MS (API-MS), such as electron spray ionization-MS (ESI-MS) and separation by liquid chromatography (such as HPLC) under reverse phase conditions. In yet other embodiments, the sulfonhydrazone is further reacted with a sulfonyl halide under alkaline conditions to derivatize hydroxyl groups in the compound. Prior formation of the sulfonhydrazide derivative protects the carbonyl bond of the compound during subsequent alkaline reaction with the sulfonyl halide.

Methods for separation and detection of ketosteroids and other carbonyl-containing compounds

Biocompatible metallic medical devices having silanized surfaces coupled to nucleophile residues that release sustained, therapeutic amounts of nitric oxide to specific sites within a mammalian body are provided. Additionally, the biocompatible metallic medical devices can also be provided with anti-thrombogenic, lubricious coatings that release sustained, therapeutic amounts of nitric oxide. Moreover, the silanized metallic devices are surprisingly durable when exposed to harsh chemical methods often needed to bind nitric oxide-releasing functional groups to nucleophile residues. Furthermore, methods are provided for producing stable, silanized, sustained nitric oxide-releasing metallic medical devices.

Nitric oxide-releasing metallic medical devices

A polymeric composition capable of releasing nitric oxide under physiological conditions which includes a biopolymer, such as a peptide, polypeptide, protein, oligonucleotide or nucleic acid, to which is bound a nitric oxide-releasing N O functional group; pharmaceutical compositions comprising the polymeric composition; and methods of treating biological disorders in which dosage with nitric oxide is therapeutic.

Nitric oxide-releasing 1-&lsqb;(2-carboxylato)pyrrolidin-1-yl&rsqb; diazen-1-ium-1,2-diolates and composition comprising same

Growing community of inventors

Thurmont, MD, United States of America

Joseph Saavedra