Merck, 5054200001, BMP Inhibitor III, LDN-212854

General description
A cell-permeable pyrazolopyrimidinylquinoline that is superior to Dorsomorphin (Cat. Nos. 171260 and 171261) and DMH1 (Cat. No. 203646) as an ATP-site-targeting, ALK1/2 inhibitor (IC₅₀ = 2.40 and 1.30 nM, respectively; [ATP] = 6 µM) with respect to both potency and selectivity over ALK3/4/5 (IC₅₀ = 0.858, 2.133, and 9.276 µM, respectively). Also a potent RIPK2 inhibitor (IC₅₀ = 6 nM) with reduced potency against ABL1/c-abl, PDGFR-β, ALK3, and PDGFR-α (IC₅₀ = 40, 68, 85.8, and 650 nM, respectively), while displaying much reduced or no inhibitory activity toward a panel of more than 190 kinases. Selectively blocks BMP7-induced/ALK2-mediated SMAD1/5/8 activation in BMPR2⁻/⁻ PASMC, but not TGF-β1-induced SMAD2 activation in PASMC. Effectively inhibits ALK2- and ALK3-mediated C2C12 osteogenic differentiation (IC₅₀ = 10 and 40.5 nM upon stimulation with respective ligand BMP6 and BMP4) in vitro and prevents constitutively active ALK2 Q207D mutation-induced heterotopic ossification in mice (6 mg/kg/12 h via i.p.) in vivo. A good complement to the ALK4/5/7-selective A-83-01 (Cat. No. 616454).
Biochem/physiol Actions
Primary Target
ALK1/2/3
Reversible: yes
Secondary Target
RIP, Abl & PDGFR
Cell permeable: yes
Packaging
Packaged under inert gas
Preparation Note
Warming may be required for complete solubilization. Material will appear as a button in the bottom of the vial.
Other Notes
Mohedas, A.H., et al. 2013. ACS Chem. Biol.8, 1291.
Legal Information
CALBIOCHEM is a registered trademark of Merck KGaA, Darmstadt, Germany
Disclaimer
Toxicity: Standard Handling (A)