LDN-214117 is a highly BMP selective compound, significantly biased toward ALK2 and its cognate ligands including BMP6 and also demonstrates a high degree of kinome selectivity and low cytotoxicity. LDN-214117 may be useful as highly selective probes of BMP-mediated cellular physiology that may provide a useful complement to the dorsomorphin class of compounds. Furthermore, this class of BMP inhibitors offers a structurally distinct template for the development of therapeutics for the treatment of BMP signaling-mediated diseases such as FOP.
|Cell lines||HepG2 hepatocarcinoma cells|
|Preparation method||Seeding cells at 25000 cells per well in 96-well plates and incubatng for 2 h at 37℃ and 5% CO2. Diluting compounds of LDN-214117 or DMSO are in DMEM and adding at ﬁnal compound concentrations of 1, 10, and 100 μM.Incubating cells for 4 and 24 h, after which the media is discarded. Cells are lysed by adding 30 μL of passive lysis buﬀer and shaken at RT for 15 min. Cell viability is determined by quantifying the ATP present in each well by adding 10 μL of Cell Titer Glo per well and measuring the light output by Spectramax L luminometer. Data is normalized to 100% viability for cells receiving only DMSO.|
|Incubation time||24 h|
|Body Surface Area (m2)||0.007||0.025||0.15||0.05||0.02||0.5|
|Animal A (mg/kg) = Animal B (mg/kg) multiplied by||Animal B Km|
|Animal A Km|
For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for resveratrol of 11.2 mg/kg.
Structure-activity relationship of 3,5-diaryl-2-aminopyridine ALK2 inhibitors reveals unaltered binding affinity for fibrodysplasia ossificans progressiva causing mutants.
Mohedas AH, et al. J Med Chem. 2014 Oct 9;57(19):7900-15. PMID: 25101911.
|Related ALK Products|
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LDK378 2Hcl (Ceritinib) is potent inhibitor against ALK with IC50 of 0.2 nM, shows 40- and 35-fold selectivity against IGF-1R and InsR, respectively.
Entrectinib (RXDX-101) is an orally bioavailable pan-TrkA/B/C, ROS1 and ALK inhibitor with IC50 ranging between 0.1 and 1.7 nM. Phase 2.
Crizotinib is inhibitor of the c-Met kinase and the NPM-ALK. Crizotinib inhibited cell proliferation in ALK-positive ALCL cells (IC50s=30 nM). Crizotinib is useful in treatment of anaplastic large-cell lymphoma.
ALK-IN-1 is an analog of AP26113 which is a potent and selective ALK inhibitor. It is also an inhibitor of EGFR.
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