Musc Foundation for Research Development

Yusuf A Hannun

Zdzislaw M Szulc

Alicja Bielawska

James S Norris

David A Schwartz

Jian-yun Dong

Besim Ogretmen

Liu Xiang

John McKillop

Jacek Bielawski

Lina M Obeid

David H Holman

Aiping Bai

Ahmed M El-Zawahry

John Mckillop

David Holman

Jian-Yun Dong

Ahmed El-Zawahry

The presently disclosed subject matter provides compounds of the formula, formula (Ia): and pharmaceutically acceptable salts thereof, wherein R, R, R, R, R, X, Y, and n are as defined herein. Also disclosed are methods for making the compounds of the formula as set forth hereinabove, their use in inhibiting acid ceramidase and ceramidase-related activity, and their use as drugs and prodrugs in the treatment and/or prevention of diseases associated with undesirable ceramidase or sphingosine kinase activity, including, but not limited to, cancer, cancer metastasis, atherosclerosis, stenosis, inflammation, asthma, and atopic dermatitis.

Lysosomotropic inhibitors of acid ceramidase

The invention provides the compounds of formula (): and pharmaceutically acceptable salts thereof, wherein R, R, R, R, A, X, Y, a, b and n are as defined herein. Also disclosed are methods for making the compounds of formula (I) and their use in treating or preventing diseases associated with cell overproliferation and dysfunctional sphingolipid signal transduction. The invention also encompasses the use of the compounds in combination with an apoptosis-signaling ligand, such as Fas ligand. Preferably, the Fas ligand is administered in the form of a gene therapy agent. 

Ceramides and apoptosis-signaling ligand

The present invention relates to cationic ceramides, their dihydro-analogs and aromatic analogs and their derivatives, comprising a pyridinium group. Also provided are methods for making cationic ceramides comprising a pyridinium group, and their use for treating or preventing diseases associated with cell overproliferation and sphingolipid signal transduction, such as cancer, inflammation, and stenosis. The compounds are also useful as mitochondritropic agents that are localized to mitochondria carrying with them chemical cargoes, such as drugs, or signaling molecules, such as fluorophores for probing organelle structure and functions.

Cationic ceramides, and analogs thereof, and their use for preventing or treating cancer

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Sullivan's Island, SC, United States of America

Yusuf A Hannun