Claims for Patent: 9,376,452

Summary for Patent: 9,376,452

Title:	Rab7 GTPase inhibitors and related methods of treatment
Abstract:	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.
Inventor(s):	Wandinger-Ness; Angela (Albuquerque, NM), Sklar; Larry (Albuquerque, NM), Agola; Jacob (Albuquerque, NM), Surviladze; Zurab (Albuquerque, NM), Aube; Jeffrey (Lawrence, KS), Golden; Jennifer (Olathe, KS), Schroeder; Chad E. (Lawrence, KS), Simpson; Denise S. (Lawrence, KS)
Assignee:	ST. UNM (Albuquerque, NM)
Application Number:	14/278,468
Patent Claims:	1. A method of treating or inhibiting colon cancer in a patient in need thereof comprising administering to said patient an anti-cancer effective amount of a compound according to the chemical structure: ##STR00047## where R.sub.1 and R.sub.2 are each independently H or CH.sub.3; when X is O, R is H; and when X=S, R is H, F, Br, OCH.sub.3 or CH.sub.3; or a pharmaceutically acceptable salt thereof, optionally in combination with an additional anticancer agent. 2. The method according to claim 1 wherein in said compound: R.sub.1 and R.sub.2 are CH.sub.3, X is S and R is H; or R.sub.1 and R.sub.2 are H, X is S and R is H; or R.sub.1 and R.sub.2 are CH.sub.3, X is O and R is H; or R.sub.1 and R.sub.2 are CH.sub.3, X is S and R is 3-MeO; or R.sub.1 and R.sub.2 are CH.sub.3, X is S and R is 4-MeO; or R.sub.1 and R.sub.2 are CH.sub.3, X is S and R is 4-F; or R.sub.1 and R.sub.2 are CH.sub.3, X is S and R is 2-Br; or R.sub.1 and R.sub.2 are CH.sub.3, X is S and R is 2-Me; or R.sub.1 and R.sub.2 are CH.sub.3, X is S and R is 4-Br, or said compound is a pharmaceutically acceptable salt thereof. 3. The method according to claim 1 wherein R.sub.1 and R.sub.2 are CH.sub.3, X is S and R is H, or a pharmaceutically acceptable salt thereof. 4. The method according to claim 1 wherein R.sub.1 and R.sub.2 are CH.sub.3, X is O and R is H, or a pharmaceutically acceptable salt thereof. 5. The method according to claim 1 wherein said compound inhibits metastasis of said cancer. 6. The method according to claim 1 wherein said compound is ##STR00048## where R.sub.1 and R.sub.2 are both CH.sub.3; X is O or S; and R is H, or a pharmaceutically acceptable salt thereof. 7. The method according to claim 1 wherein said additional anticancer agent is a PARP inhibitor, 5-fluorouracil, cisplatin, carboplatin, bevacizumab, oxaliplatin, erbitux, cetuximab, panitumumab, capecitabine or a mixture thereof. 8. The method according to claim 2 wherein said additional anticancer agent is a PARP inhibitor, 5-fluorouracil, cisplatin, carboplatin, bevacizumab, oxaliplatin, erbitux, cetuximab, panitumumab, capecitabine or a mixture thereof. 9. The method according to claim 3 wherein said additional anticancer agent is a PARP inhibitor, 5-fluorouracil, cisplatin, carboplatin, bevacizumab, oxaliplatin, erbitux, cetuximab, panitumumab, capecitabine or a mixture thereof. 10. The method according to claim 4 wherein said additional anticancer agent is a PARP inhibitor, 5-fluorouracil, cisplatin, carboplatin, bevacizumab, oxaliplatin, erbitux, cetuximab, panitumumab, capecitabine or a mixture thereof. 11. The method according to claim 5 wherein said additional anticancer agent is a PARP inhibitor, 5-fluorouracil, cisplatin, carboplatin, bevacizumab, oxaliplatin, erbitux, cetuximab, panitumumab, capecitabine or a mixture thereof. 12. The method according to claim 6 wherein said additional anticancer agent is a PARP inhibitor, 5-fluorouracil, cisplatin, carboplatin, bevacizumab, oxaliplatin, erbitux, cetuximab, panitumumab, capecitabine or a mixture thereof.

Details for Patent 9,376,452

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Eli Lilly And Company	ERBITUX	cetuximab	Injection	125084	02/12/2004		2031-03-02
Eli Lilly And Company	ERBITUX	cetuximab	Injection	125084	03/28/2007		2031-03-02
Genentech, Inc.	AVASTIN	bevacizumab	Injection	125085	02/26/2004		2031-03-02
Amgen, Inc.	VECTIBIX	panitumumab	Injection	125147	09/27/2006		2031-03-02