Claims for Patent: 9,649,305

Summary for Patent: 9,649,305

Title:	PFKFB3 inhibitor and methods of use as an anti-cancer therapeutic
Abstract:	A novel compound, (E)-1-(pyridyn-4-yl)-3-(7-(trifluoromethyl)quinolin-2-yl)-prop-2-en-1-one- , is provided herein. (E)-1-(pyridyn-4-yl)-3-(7-(trifluoromethyl)quinolin-2-yl)-prop-2-en-1-one is an inhibitor of 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3) with surprisingly superior efficacy and pharmacodynamic properties in vitro and in vivo. Also provided are pharmaceutical compositions including the compound and methods of use of the compound in treating cancer and tumors in vivo, as well as inhibiting glycolytic flux and PFKFB3 enzymatic activity in cells. ##STR00001##
Inventor(s):	Tapolsky; Gilles H. (Louisville, KY), Chand; Pooran (Birmingham, AL)
Assignee:	Advanced Cancer Therapeutics, LLC (Louisville, KY)
Application Number:	14/388,983
Patent Claims:	1. A compound for the treatment of cancer, consisting of (E)-1-(pyridyn-4-yl)-3-(7-(trifluoromethyl)quinolin-2-yl)-prop-2-en-1-one- , or a pharmaceutically acceptable salt thereof, having the formula: ##STR00027## 2. The compound of claim 1, wherein the cancer is selected from the group consisting of glioblastoma multiforme, skin cancers, connective tissue cancers, adipose cancers, breast cancers, lung cancers, stomach cancers, pancreatic cancers, ovarian and reproductive organ cancers, cervical cancers, uterine cancers, anogenital cancers, kidney cancers, bladder cancers, liver cancers, colorectal or colon cancers and digestive (GI) tract cancers, prostate cancers and reproductive organ cancers, central nervous system (CNS) cancers, retinal cancer, blood, and lymphoid cancers, and head and neck cancers. 3. A pharmaceutical composition for the treatment of cancer, comprising: (a) an effective amount of (E)-1-(pyridyn-4-yl)-3-(7-(trifluoromethyl)quinolin-2-yl)-prop-2-en-1-one or a pharmaceutically acceptable salt thereof; and (b) at least one pharmaceutically acceptable carrier. 4. The pharmaceutical composition of claim 3, further comprising a second anti-cancer agent. 5. The pharmaceutical composition of claim 4, wherein the second anti-cancer agent is selected from the group consisting of paclitaxel, docetaxel, cis-platin, carboplatin, oxaliplatin, doxorubicin, vincristine, vinblastine, 5-FU, irinotican, methotraxate, leucovorin, bevacizumab, cetuximab, sutinibib, imatinib, temozolomide, and gemcitabine. 6. The pharmaceutical composition of claim 3, wherein the cancer is selected from the group consisting of glioblastoma multiforme, skin cancers, connective tissue cancers, adipose cancers, breast cancers, lung cancers, stomach cancers, pancreatic cancers, ovarian and reproductive organ cancers, cervical cancers, uterine cancers, anogenital cancers, kidney cancers, bladder cancers, liver cancers, colorectal or colon cancers and digestive (GI) tract cancers, prostate cancers and reproductive organ cancers, central nervous system (CNS) cancers, retinal cancer, blood, and lymphoid cancers, and head and neck cancers. 7. A method of treating cancer, the method comprising administering to a subject in need thereof an effective amount of (E)-1-(pyridyn-4-yl)-3-(7-(trifluoromethyl)quinolin-2-yl)-prop-2-en-1-one or a pharmaceutically acceptable salt thereof. 8. The method of claim 7, wherein the cancer is selected from the group consisting of glioblastoma multiforme, skin cancers, connective tissue cancers, adipose cancers, breast cancers, lung cancers, stomach cancers, pancreatic cancers, ovarian and reproductive organ cancers, cervical cancers, uterine cancers, anogenital cancers, kidney cancers, bladder cancers, liver cancers, colorectal or colon cancers and digestive (GI) tract cancers, prostate cancers and reproductive organ cancers, central nervous system (CNS) cancers, retinal cancer, blood, and lymphoid cancers, and head and neck cancers. 9. The method of claim 8, further comprising administering a second anti-cancer agent. 10. The method of claim 9, wherein the second anti-cancer agent is selected from the group consisting of paclitaxel, docetaxel, cis-platin, carboplatin, oxaliplatin, doxorubicin, vincristine, vinblastine, 5-FU, irinotican, methotraxate, leucovorin, bevacizumab, cetuximab, sutinibib, imatinib, temozolomide, and gemcitabine. 11. The method of claim 10, wherein the second anti-cancer agent is co-administered with (E)-1-(pyridyn-4-yl)-3-(7-(trifluoromethyl)quinolin-2-yl)-prop-2-en-1-one- . 12. A method of treating a tumor, the method comprising administering to a subject in need thereof an effective amount of (E)-1-(pyridyn-4-yl)-3-(7-(trifluoromethyl)quinolin-2-yl)-prop-2-en-1-one or a pharmaceutically acceptable salt thereof. 13. The method of claim 12, further comprising administering a second anti-cancer agent. 14. The method of claim 13, wherein the second anti-cancer agent is selected from the group consisting of paclitaxel, docetaxel, cis-platin, carboplatin, oxaliplatin, doxorubicin, vincristine, vinblastine, 5-FU, irinotican, methotraxate, leucovorin, bevacizumab, cetuximab, sutinibib, imatinib, temozolomide, and gemcitabine. 15. The method of claim 14, wherein the second anti-cancer agent is co-administered with (E)-1-(pyridyn-4-yl)-3-(7-(trifluoromethyl)quinolin-2-yl)-prop-2-en-1-one- . 16. A method of inhibiting glycolytic flux in a cell, the method comprising contacting the cell with an effective amount of (E)-1-(pyridyn-4-yl)-3-(7-(trifluoromethyl)quinolin-2-yl)-prop-2-en-1-one or a pharmaceutically acceptable salt thereof. 17. A method of inhibiting enzymatic activity of PFKFB3 in a cell, the method comprising contacting the cell with an effective amount of (E)-1-(pyridyn-4-yl)-3-(7-(trifluoromethyl)quinolin-2-yl)-prop-2-en-1-one or a pharmaceutically acceptable salt thereof.

Details for Patent 9,649,305

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Eli Lilly And Company	ERBITUX	cetuximab	Injection	125084	02/12/2004		2039-02-26
Eli Lilly And Company	ERBITUX	cetuximab	Injection	125084	03/28/2007		2039-02-26
Genentech, Inc.	AVASTIN	bevacizumab	Injection	125085	02/26/2004		2039-02-26