Technology ID
TAB-3540
Pyrazolo[1,5-a]pyrimidine Derivatives as Selective ALK Kinases Inhibitors for Inhibition of the Bone Morphogenetic Proteins Signaling Pathway for Treatment of Fibrodysplasia Ossificans Progressiva
E-Numbers
E-299-2012-0
Lead Inventor
Grewal, Gurmit
Lead IC
NCATS
Co-Inventors
Lee, Arthur
Xu, Xin
Shen, Min
McKew, John
Bloch, Kenneth
Yu, Paul
Cuny, Gregory
Peterson, Randall
Alimardanov, Asaf
ICs
NCATS
Applications
Therapeutics
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.
Commercial Applications
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).
Competitive Advantages
- 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
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