Sigma-Aldrich BMP Inhibitor Iii Ldn-2128

Assay

≥98% (HPLC)

Quality Level

100

Form

solid

Manufacturer/Tradename

Calbiochem^®

Storage Condition

OK to freeze
protect from light

Color

pale yellow

Solubility

DMSO: 25 mg/mL

Storage Temp.

2-8°C

Smiles String

C1CN(CCN1)C2=CC=C(C=C2)C3=CN4C(=C(C=N4)C5=C6C=CC=NC6=CC=C5)N=C3

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) and little inhibitory activity toward a panel of more than 190 kinases. Effectively inhibits ALK2- and ALK3-mediated C2C12 osteogenic differentiation (IC₅₀= 10 and 40.5 nM, respectively)in vitroand prevents constitutively active ALK2 Q207D mutant-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).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 vitroand 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

Cell permeable: yesPrimary Target
ALK1/2/3Reversible: yesSecondary Target
RIP, Abl & PDGFR

Packaging

Packaged under inert gas

Warning

Toxicity: Standard Handling (A)

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.CALBIOCHEM is a registered trademark of Merck KGaA, Darmstadt, Germany