BMP inhibitors and methods of use thereof

• US 10,017,516 B2
• Filed: 05/18/2017
• Issued: 07/10/2018
• Est. Priority Date: 03/14/2013
• Status: Active Grant

• Current Assignee: Brigham and Women's Hospital Incorporated, Department of Health and Human Services (State of Victoria)
• Original Assignee: Brigham and Women's Hospital Incorporated, The United States of America As Represented By The Secretary of Agriculture
• Inventors: Alimardanov, Asaf, Cuny, Gregory D., Grewal, Gurmit S., Lee, Arthur, McKew, John C., Mohedas, Agustin H., Shen, Min, Xu, Xin, Yu, Paul B.
• Primary Examiner(s): Habte, Kahsay
• Application Number:
  US15/598,540
• Publication Number:
  US 20170334918A1
• Time in Patent Office: 418 Days
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Abstract

The present invention provides small molecule inhibitors of BMP signaling. These compounds may be used to modulate cell growth, differentiation, proliferation, and apoptosis, and thus may be useful for treating diseases or conditions associated with BMP signaling, including inflammation, cardiovascular disease, hematological disease, cancer, and bone disorders, as well as for modulating cellular differentiation and/or proliferation. These compounds may also be used to reduce circulating levels of ApoB-100 or LDL and treat or prevent acquired or congenital hypercholesterolemia or hyperlipoproteinemia; diseases, disorders, or syndromes associated with defects in lipid absorption or metabolism; or diseases, disorders, or syndromes caused by hyperlipidemia.

Claims

1. A method of treating a disease or condition in a subject that would benefit from inhibition of Bone Morphogenetic Protein (BMP) signaling, comprising administering to the subject a compound having a structure of Formula I or a pharmaceutically acceptable salt, ester, or prodrug thereof,

2. The method of claim 1, wherein the disease or condition is selected from breast carcinoma, prostate carcinoma, renal cell carcinoma, bone metastasis, lung metastasis, osteosarcoma, and multiple myeloma.

3. The method of claim 1, wherein the disease or condition is ankylosing spondylitis.

4. The method of claim 1, where the disease or condition is fibrodysplasia ossificans progressiva or anemia.

5. A method of inhibiting Bone Morphogenetic Protein (BMP) signaling in a subject, comprising administering to the subject a compound having a structure of Formula I or a pharmaceutically acceptable salt, ester, or prodrug thereof,