Cancer chemotherapy often provides temporary clinical improvement. However, tumor cells that survive the initial treatment often develop into cancers with multiple drug resistance (MDR). This is most often mediated by increased levels of the transport protein P-glycoprotein (PgP). A related family… More

Current treatment protocols for AIDS involve combinations of nucleoside analogs and HIV protease inhibitors, but are not successful in curing the disease. The drug transport protein, P-glycoprotein (Pgp) effluxes a wide variety of drugs, including all FDA-approved protease inhibitors. A growing… More

The goal of this project is to identify and characterize novel inhibitors of human N-myristoyltransferase (NMT) that are effective as cancer therapeutic agents. Studies have shown that NMT catalyzes critical steps in the processing of several oncoproteins, and that genetic inhibition of this process… More

DESCRIPTION (provided by applicant): The long-term goal of this program is to identify and evaluate novel inhibitors of human sphingosine kinase (SK) as anticancer therapeutic agents. We have focused on SK as a innovative molecular target for cancer therapy because of its critical role in… More

DESCRIPTION (provided by applicant): The goal of this program is to develop novel inhibitors of human palmitoyl acyltransferases (PATs) that are effective as cancer therapeutic agents. PATs represent new targets for anticancer drug development because of their pivotal roles in regulating the… More

DESCRIPTION (provided by applicant): The long-term goal of this program is to identify and develop novel inhibitors of human sphingosine kinase (SK) that are effective as therapeutic agents. Because of its critical role in sphingolipid metabolism and angiogenesis, we have focused on SK as an… More

DESCRIPTION (provided by applicant): The long-term goal of this program is to develop novel inhibitors of human sphingosine kinase (SK) that are effective as therapeutic agents. Because of its critical role in sphingolipid metabolism, we have focused on SK as an innovative molecular target for the… More

DESCRIPTION (provided by applicant): The long-term goal of this program is to develop novel inhibitors of human sphingosine kinase (SK) that are effective for the treatment of arthritis. Sphingolipids are being increasingly recognized as key mediators of apoptosis, stress responses, cell… More

DESCRIPTION (provided by applicant): The goal of this program is to develop novel inhibitors of human sphingosine kinase (SK) that are effective as therapeutic agents. Because of its critical role in sphingolipid metabolism, we have focused on SK as an innovative molecular target for the development… More

DESCRIPTION (provided by applicant): Principal Investigator/Program Director: French, Kevin J. Abstract: The long-term goal of this program is to develop inhibitors of human sphingosine kinase (SK) that are effective as therapeutic agents. Because of its critical role in sphingolipid metabolism, we… More

DESCRIPTION (provided by applicant): The goal of this program is to develop novel inhibitors of human sphingosine kinase (SK) that are effective as therapeutic agents for retinal and choroidal vascular diseases. Because of its critical role in sphingolipid metabolism, we have focused on SK as an… More

DESCRIPTION (provided by applicant): Sphingolipids are being increasingly recognized as key mediators of inflammatory cascades of critical importance in multiple diseases, including rheumatoid arthritis and osteoarthritis. Most importantly, sphingosine 1-phosphate produced by sphingosine kinase… More

DESCRIPTION (provided by applicant): Derivatives of camptothecin (CPT) that inhibit Topoisomerase I (Top1) activity have demonstrated clinical utility in the treatment of various cancers. However, limitations in CPT pharmaceutical properties have driven th e search for new CPT-like poisons that… More

DESCRIPTION (provided by applicant): Severe shortages of donor organs limit the use of orthotopic liver transplantation (LT), the only proven therapy for end-stage liver diseases. Primary non-function (PNF) of liver grafts after transplantation typically r esults in recipient death or necessitates… More

DESCRIPTION (provided by applicant): The Kaposi's sarcoma-associated herpesvirus (KSHV) is the causative agent of cancers arising preferentially within immune compromised hosts, including patients infected with HIV. One of these cancers, a clonal B-cell malignancy known as primary effusion… More

DESCRIPTION (provided by applicant): The goal of this program is to develop novel inhibitors of human neutral ceramidase (ASAH2) that are effective as therapeutic agents for Inflammatory Bowel Diseases (IBDs). Sphingolipids are being increasingly recognized as key mediators of inflammation, and are… More