Claims for Patent: 10,329,246

Summary for Patent: 10,329,246

Title:	RUNX2 transcription factor inhibitors and uses thereof
Abstract:	Provide herein are compounds with a general chemical structure of: ##STR00001## Substituents R.sub.1 and R.sub.2 independently are H, Cl, F, Br, CH.sub.3, CF.sub.3, SH, --N(C.sub.1-3alkyl).sub.2, --NHC(O)C.sub.1-3alkyl, or --NHC(O)C.sub.5-7cycloalkyl, substituent R.sub.3 is H or C.sub.1-3 alkyl and R4 is a bridged cycloalkene such as a bridged cyclohexene or a bridge-substituted cyclohexene. The compounds are therapeutics to treat a cancer, such as breast cancer, or metastatic cancers, to inhibit RUNX2 activity, such as protein expression, in a cancer cell and to increase survival of a subject with breast cancer.
Inventor(s):	Passaniti; Antonino (White Hall, MD), Alexander, Jr.; MacKerell D. (Baltimore, MD)
Assignee:	University of Maryland, Baltimore (Baltimore, MD) The United States of America as represented by the Department of Veterans Affairs (Washington, DC)
Application Number:	15/708,872
Patent Claims:	1. A method for treating breast cancer in a subject, comprising: administering to the subject a dose of one or more compounds having the chemical structure ##STR00012## wherein R.sub.1 and R.sub.2 independently are H, Cl, F, Br, CH.sub.3, CF.sub.3, SH, --N(C.sub.1-3alkyl).sub.2, --NHC(O)C.sub.1-3alkyl, or --NHC(O)C.sub.5-7cycloalkyl; R.sub.3 is H or C.sub.1-3 alkyl; and R.sub.4 is ##STR00013## or a pharmaceutically acceptable salt thereof effective to inhibit a RUNX2 activity, thereby treating the breast cancer. 2. The method of claim 1, further comprising administering one or more other cancer drugs. 3. The method of claim 2, wherein the other cancer drugs are Herceptin, Lapatinib, or E-Cadherin monoclonal antibody (DECMA1) antibody. 4. The method of claim 1, wherein the breast cancer is a metastatic cancer. 5. A method for treating a metastatic cancer originating from a breast cancer in a subject, comprising: administering to the subject a dose of one or more compounds having the chemical structure ##STR00014## wherein R.sub.1 and R.sub.2 independently are H, Cl, F, Br, CH.sub.3, CF.sub.3, SH, --N(C.sub.1-3alkyl).sub.2, --NHC(O)C.sub.1-3alkyl, or --NHC(O)C.sub.5-7cycloalkyl; R.sub.3 is H or C.sub.1-3 alkyl; and R.sub.4 is ##STR00015## or a pharmaceutically acceptable salt thereof effective to inhibit a RUNX2 activity, thereby treating the metastatic cancer. 6. The method of claim 5, further comprising administering one or more other cancer drugs. 7. The method of claim 6, wherein the other cancer drugs are Herceptin, Lapatinib, or E-Cadherin monoclonal antibody (DECMA1). 8. A method for treating breast cancer in a subject, comprising administering to the subject a dose of a compound having the chemical structure: ##STR00016## or a pharmaceutically acceptable salt thereof effective to inhibit RUNX2, thereby treating the breast cancer. 9. The method of claim 8, further comprising administering one or more other cancer drugs. 10. The method of claim 9, wherein the other cancer drugs are Herceptin, Lapatinib, or E-Cadherin monoclonal antibody (DECMA1). 11. The method of claim 8, wherein the breast cancer comprises metastases thereof. 12. The method of claim 8, wherein treatment inhibits metastasis of the breast cancer. 13. The method of claim 1, wherein R.sub.3 is H. 14. The method of claim 1, wherein R.sub.1 and R.sub.2 are independently H, Cl, Br, or --NHC(O)CH.sub.3, R.sub.3 is H and R.sub.4 is ##STR00017## 15. The method of claim 1, wherein R.sub.1 and R.sub.2 are independently H, Cl, CH.sub.3, --NHC(O)CH.sub.3, --NHC(O)cyclohexane, or N(CH.sub.3).sub.2, R.sub.3 is H and R.sub.4 is ##STR00018## 16. The method of claim 1, wherein R.sub.1 and R.sub.2 are each Cl and R.sub.3 is H. 17. The method of claim 1, wherein the chemical structure is: ##STR00019## ##STR00020## 18. The method of claim 5, wherein R.sub.3 is H. 19. The method of claim 5, wherein R.sub.1 and R.sub.2 are independently H, Cl, Br, or --NHC(O)CH.sub.3, R.sub.3 is H and R.sub.4 is ##STR00021## 20. The method of claim 5, wherein R.sub.1 and R.sub.2 are independently H, Cl, CH.sub.3, --NHC(O)CH.sub.3, --NHC(O)cyclohexane, or N(CH.sub.3).sub.2, R.sub.3 is H and R.sub.4 is ##STR00022## 21. The method of claim 5, wherein R.sub.1 and R.sub.2 are each Cl and R.sub.3 is H. 22. The method of claim 5, wherein the chemical structure is: ##STR00023## ##STR00024##

Details for Patent 10,329,246

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Genentech, Inc.	HERCEPTIN	trastuzumab	For Injection	103792	09/25/1998		2035-03-19
Genentech, Inc.	HERCEPTIN	trastuzumab	For Injection	103792	02/10/2017		2035-03-19