University of Kansas

Stc.unm

Southern Research Institute

St. Unm

Denise S Simpson

Jennifer Elizabeth Golden

Larry A Sklar

Jeffrey Aube

Angela Wandinger-Ness

Zurab Surviladze

Chad Schroeder

Jacob Ongudi Agola

Tudor Oprea

Daniel Patrick Flaherty

Laurie Hudson

Jeffrey Aubé

Lynn Rasmussen

Julica J Noth

Daljit S Matharu

William E Severson

Rasmussen Lynn

The present invention relates to molecules which function as selective modulators (i.e., inhibitors and agonists, preferably inhibitors) of the Ras-homologous (Rho) family of small GTPases, in particular, Cdc42 GTPase and their use to treat diseases, for example cancers, including metastatic cancer, where Cdc42 GTPase is overexpressed or hyperactivated, genetic and acquired diseases where activation of Cdc42 GTPase plays a pivotal role (e.g., neurodegenerative diseases), rheumatoid arthritis, atherosclerosis, diabetes type I, autosomal polycystic kidney diease, cystic kidney disease, precystic kidney disease and microbial infections. Additionally, compounds according to the present invention may be used to inhibit rejection (graft host response) in transplant patients (pursuant to transplantation), to promote immunosuppression, anti-inflammatory response and to mobilize stem cell (migration) in patients in need, among others.

Modulators of GTPase and use in relevant treatment

Described herein are compounds, pharmaceutical compositions and methods for treating a respiratory syncytial virus infection in a subject, or for inhibiting replication of respiratory syncytial virus.

Inhibitors of respiratory syncytial virus

This invention relates to compounds and their use as inhibitors or activators of Rab7 GTPase to treat or prevent the onset of Rab 7 GTPase-associated disorders such as neuropathies, cancer, metabolic diseases of bone and lipid storage. The invention is also applicable to infectious diseases where Rab7 is inactivated or its protein-protein interactions are modulated to facilitate intracellular survival of pathogens. The compound described acts as a competitive inhibitor of nucleotide binding and as such also has utility as a scaffold for targeting other small GTPases. In one aspect, methods of treatment of the invention are used to treat or prevent the onset of hereditary sensory neuropathies such as Charcot-Marie-Tooth type 2B disease. Related pharmaceutical compositions, assays, and drug screens are also provided.

Rab7 GTPase inhibitors and related methods of treatment

Growing community of inventors

Lawrence, KS, United States of America

Denise S Simpson