The Johns Hopkins University

Fasgen, Inc.

Francis P Kuhajda

Gary R Pasternack

Craig Arthur Townsend

James D Dick

Nicole M Parrish

Jagan N Thurpari

Leslie E Landree

Neelakandha S Mani

Jill M McFadden

Susan M Medghalchi

Jagan Thupari

Gabrielle Ronnett

Craig A Townsend

A pharmaceutical composition comprising a pharmaceutical diluent and a compound of formula IV wherein R=H, C-Calkyl, cycloalkyl, alkenyl, aryl, arylalkyl, or alkylaryl, &#x2014;CHOR, &#x2014;C(O)R, &#x2014;CO(O)R, &#x2014;C(O)NRR, &#x2014;CHC(O)R, or &#x2014;CHC(O)NHR, where Rand Rare each independently H, C-Calkyl, cycloalkyl, alkenyl, aryl, arylalkyl, or alkylaryl, optionally containing one or more halogen atoms. R=&#x2014;OH, &#x2014;OR, &#x2014;OCHC(O)R, &#x2014;OCHC(O)NHR, &#x2014;OC(O)R, &#x2014;OC(O)OR, &#x2014;OC(O)NHNH&#x2014;R, or &#x2014;OC(O)NRR, where Rand Rare each independently H, C-Calkyl, cycloalkyl, alkenyl, aryl, arylalkyl, or alkylaryl, and where Rand Rcan each optionally contain halogen atoms; Rand R, the same or different from each other, are C-Calkyl, cycloalkyl, alkenyl, aryl, arylalkyl, or alkylaryl. Methods of using such formulations for the treatment of cancer, to effect weight loss, to treat microbially-based infections, to inhibit neuropeptide-Y and/or fatty acid synthase, and to stimulate CPT-1. 

Compounds, pharmaceutical compositions containing same, and methods of use for same

This invention provides methods and compositions for inducing weight loss and maintaining optimum weight comprising administering an agent that stimulates carnitine palmitoyl transferase-1 (CPT-1) activity to the patient in need, including human patients. These methods do not require inhibition of fatty acid synthesis. In particular, this invention provides methods for development of therapeutics that selectively enhance fatty acid oxidation, increase energy production, and reduce adiposity while preserving lean mass, through the pharmacological stimulation of CPT-1 activity. In a preferred mode, the agent is administered in an amount sufficient to increase fatty acid oxidation. In another preferred mode, the agent is administered in an amount sufficient to antagonize malonyl CoA inhibition of CPT-1. In yet another preferred mode, the agent is administered in an amount sufficient to increase malonyl CoA level.

Stimulation of CPT-1 as a means to reduce weight

This invention provides compounds and methods for treating, with said compound, a mycobacterial infection by administering to an animal a pharmaceutical composition containing a compound having the formula R&#x2014;SO-Z-CO&#x2014;Y, where R is an alkyl groups having 6-20 carbon atoms, unsaturated hydrocarbon groups having 6-20 carbon atoms, or alkyl groups having 6-20 carbon atoms interrupted by at least one aromatic ring; Z is &#x2014;CH&#x2014;, &#x2014;CHCH&#x2014;, &#x2014;NH&#x2014;NH&#x2014;, &#x2014;O&#x2014;, &#x2014;&#x2014;NH&#x2014;, &#x2014;O&#x2014;NH&#x2014;, &#x2014;CH&#x2014;NH&#x2014;, &#x2014;CH&#x2014;O&#x2014;, &#x2014;NH&#x2014;O&#x2014;, &#x2014;NH&#x2014;CH&#x2014;, &#x2014;O&#x2014;CH&#x2014;, and &#x2014;CH&#x2550;CH&#x2014;; Y is &#x2014;NH, &#x2014;O&#x2014;CH&#x2014;CH, &#x2014;CO&#x2014;CO&#x2014;O&#x2014;CH, and &#x2014;O&#x2014;CH; and n is 1 or 2. It has been discovered that these compounds treat microbially-based infections caused by corynebacteria, nocardiae, rhodococcus, and mycobacteria. These compounds may be used to treat mycobacterial cells, such as, drug resistant, and pathogenicsp.

Antimicrobial compounds

This invention provides methods for treating a mycobacterial infection by administering to an animal a pharmaceutical composition containing a compound having the formula R&mdash;SO &mdash;Z&mdash;CO&mdash;Y, where R is an alkyl group having 6-20 carbons; Z is a radical selected from &mdash;CH &mdash;, &mdash;O&mdash;, and &mdash;NH&mdash;, two of these radicals coupled together, or &mdash;CH &boxH;CH &mdash;; Y is &mdash;NH , O&mdash;CH &mdash;C H , &mdash;CO&mdash;CO&mdash;O&mdash;CH , or O&mdash;CH ; and n is 1 or 2. It has been discovered that these compounds inhibit growth of microbial cells which synthesize &agr;-substitued, &bgr;-hydroxy fatty acids, particularly corynemycolic acid, nocardic acid, and mycolic acid. These compounds may be used to inhibit growth of mycobacterial cells, such as drug-resistant and

Inhibition of fatty acid synthase as a means to reduce adipocyte mass

A method of determining the prognosis of a solid tumor is provided, in which a sample from a patient bearing a tumor is assayed for the presence of a protein which is immunologically cross-reactive with the hpr gene product, but not with haptoglobin 1 or haptoglobin 2. Also provided is a method for preparing antibodies specific for this diagnostic marker which correlates with early relapse and metastasis of breast and other cancers. The marker can be detected using immunological methods employing antibodies specific for Hpr protein and not cross-reactive with haptoglobins 1 or 2.

Antibodies which specifically bind a cancer related antigen

Cancer related antigen

A method of determining the prognosis of a solid tumor is provided, in which a sample from a patient bearing a tumor is assayed for the presence of a protein which is immunologically cross-reactive with the hr gene product, but not with haptoglobin 1 or haptoglobin 2. Also provided is a method for preparing antibodies specific for this diagnostic marker which correlates with early relapse and metastasis of breast and other cancers. The marker can be detected using immunological methods employing antibodies specific for Hpr protein and not cross-reactive with haptoglobins 1 or 2.

Fatty acid synthase (FAS) is overexpressed in carcinomas with poor prognosis, but little FAS expression is identified in normal tissues Inhibition of fatty acid synthesis is selectively toxic to carcinoma cells, while normal cells with low FAS activity are resistant. This invention provides a method of treating cancer patients where fatty acid synthesis by cells of the patient's tumor is inhibited with resultant interruption of the disease process.

Chemotherapy for cancer by inhibiting the fatty acid biosynthetic pathway

Fatty acid synthase (FAS) is overexpressed by certain infectious organisms that are resistant to most currently available antibiotics. Contrarywise, little FAS expression is identified in patient tissues. Inhibition of fatty acid synthesis is thus selectively toxic to invasive cells, while patient cells with low FAS activity are resistant. This invention provides a method of treating septic patients where fatty acid synthesis by invading cells is inhibited with resultant interruption of the disease process.

Growing community of inventors

Lutherville, MD, United States of America

Francis P Kuhajda