LDN-214117   Click here for help

GtoPdb Ligand ID: 8481

Synonyms: compound 10 [PMID: 25101911] | LDN214117
Compound class: Synthetic organic
Comment: LDN-214117 is an experimental activin A receptor, type I (ACVR1 aka BMP type I receptor kinase ALK2) inhibitor [2]. LDN-214117 may provide a structural template for the preclinical development of novel therapeutics for conditions such as fibrodysplasia ossificans progressiva (FOP), characterised by inappropriate BMP signalling, and reported to be caused by gain-of-function ALK2 mutations [1,3-5].
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2D Structure
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Physico-chemical Properties
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Hydrogen bond acceptors 3
Hydrogen bond donors 1
Rotatable bonds 6
Topological polar surface area 55.85
Molecular weight 419.22
XLogP 4.17
No. Lipinski's rules broken 0
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Canonical SMILES COc1cc(cc(c1OC)OC)c1cc(cnc1C)c1ccc(cc1)N1CCNCC1
Isomeric SMILES COc1cc(cc(c1OC)OC)c1cc(cnc1C)c1ccc(cc1)N1CCNCC1
InChI InChI=1S/C25H29N3O3/c1-17-22(19-14-23(29-2)25(31-4)24(15-19)30-3)13-20(16-27-17)18-5-7-21(8-6-18)28-11-9-26-10-12-28/h5-8,13-16,26H,9-12H2,1-4H3
1. Kaplan FS, Xu M, Seemann P, Connor JM, Glaser DL, Carroll L, Delai P, Fastnacht-Urban E, Forman SJ, Gillessen-Kaesbach G et al.. (2009)
Classic and atypical fibrodysplasia ossificans progressiva (FOP) phenotypes are caused by mutations in the bone morphogenetic protein (BMP) type I receptor ACVR1.
Hum Mutat, 30 (3): 379-90. [PMID:19085907]
2. Mohedas AH, Wang Y, Sanvitale CE, Canning P, Choi S, Xing X, Bullock AN, Cuny GD, Yu PB. (2014)
Structure-activity relationship of 3,5-diaryl-2-aminopyridine ALK2 inhibitors reveals unaltered binding affinity for fibrodysplasia ossificans progressiva causing mutants.
J Med Chem, 57 (19): 7900-15. [PMID:25101911]
3. Nakahara Y, Katagiri T, Ogata N, Haga N. (2014)
ACVR1 (587T>C) mutation in a variant form of fibrodysplasia ossificans progressiva: second report.
Am J Med Genet A, 164A (1): 220-4. [PMID:24259422]
4. Pignolo RJ, Shore EM, Kaplan FS. (2011)
Fibrodysplasia ossificans progressiva: clinical and genetic aspects.
Orphanet J Rare Dis, 6: 80. [PMID:22133093]
5. Shore EM, Xu M, Feldman GJ, Fenstermacher DA, Cho TJ, Choi IH, Connor JM, Delai P, Glaser DL, LeMerrer M et al.. (2006)
A recurrent mutation in the BMP type I receptor ACVR1 causes inherited and sporadic fibrodysplasia ossificans progressiva.
Nat Genet, 38 (5): 525-7. [PMID:16642017]