Lee, Arthur (NCATS)
Xu, Xin (NCATS)
Shen, Min (NCATS)
McKew, John (NCATS)
Bloch, Kenneth (Massachusetts General Hospital (MGH))
Yu, Paul (Massachusetts General Hospital (MGH))
Cuny, Gregory (Massachusetts General Hospital (MGH))
Peterson, Randall (Massachusetts General Hospital (MGH))
Alimardanov, Asaf (NCATS)
This technology includes compounds which are selective inhibitors of anaplastic lymphoma kinases (ALK1, ALK2, ALK3 and ALK6), which inhibit these ALKs with low nanomolar potency. These compounds could be developed as a treatment of Fibrodysplasia ossificans progressiva (FOP) and other BMP-related diseases. FOP is a rare congenital disease with no current treatment options. Since the disease is driven by constitutively active ALK2, inhibition of ALK2 would be like hitting the Achilles’ heel of the disease and would potentially be an efficacious therapy for FOP patients. It has also been shown that inhibition of these ALKs is efficacious in animal disease models of anemia of inflammation. Compounds of this invention inhibit ALK2, as well as ALK1, ALK3 and ALK6, with nanomolar potency, both in enzyme and cell assays.
A treatment for FOP and anemia of inflammation, as well as BMP driven diseases (certain cancers, cardio-vascular disease, inflammation, hematological disease and bone disorders).
- There are currently no effective treatments available for FOP
- Current BMP inhibitor in development is metabolized by Cyp enzymes and aldehyde oxidase and has the potential of generating an aniline-metabolite which could be potentially toxic and difficult to predict a safe and efficacious dose