ml347 has been researched along with dorsomorphin* in 2 studies
2 other study(ies) available for ml347 and dorsomorphin
| Article | Year |
|---|---|
Synthesis and structure-activity relationships of a novel and selective bone morphogenetic protein receptor (BMP) inhibitor derived from the pyrazolo[1.5-a]pyrimidine scaffold of dorsomorphin: the discovery of ML347 as an ALK2 versus ALK3 selective MLPCN
A structure-activity relationship of the 3- and 6-positions of the pyrazolo[1,5-a]pyrimidine scaffold of the known BMP inhibitors dorsomorphin, 1, LDN-193189, 2, and DMH1, 3, led to the identification of a potent and selective compound for ALK2 versus ALK3. The potency contributions of several 3-position substituents were evaluated with subtle structural changes leading to significant changes in potency. From these studies, a novel 5-quinoline molecule was identified and designated an MLPCN probe molecule, ML347, which shows >300-fold selectivity for ALK2 and presents the community with a selective molecular probe for further biological evaluation. Topics: Activin Receptors, Type I; Animals; Bone Morphogenetic Protein Receptors; Half-Life; Heterocyclic Compounds, 2-Ring; Humans; Mice; Protein Binding; Protein Isoforms; Pyrazoles; Pyrimidines; Quinolines; Rats; Structure-Activity Relationship | 2013 |
Structure-activity relationship study of bone morphogenetic protein (BMP) signaling inhibitors.
A structure-activity relationship study of dorsomorphin, a previously identified inhibitor of SMAD 1/5/8 phosphorylation by bone morphogenetic protein (BMP) type 1 receptors ALK2, 3, and 6, revealed that increased inhibitory activity could be accomplished by replacing the pendent 4-pyridine ring with 4-quinoline. The activity contributions of various nitrogen atoms in the core pyrazolo[1,5-a]pyrimidine ring were also examined by preparing and evaluating pyrrolo[1,2-a]pyrimidine and pyrazolo[1,5-a]pyridine derivatives. In addition, increased mouse liver microsome stability was achieved by replacing the ether substituent on the pendent phenyl ring with piperazine. Finally, an optimized compound 13 (LDN-193189 or DM-3189) demonstrated moderate pharmacokinetic characteristics (e.g., plasma t(1/2)=1.6h) following intraperitoneal administration in mice. These studies provide useful molecular probes for examining the in vivo pharmacology of BMP signaling inhibition. Topics: Animals; Bone Morphogenetic Protein Receptors; Bone Morphogenetic Proteins; Combinatorial Chemistry Techniques; Female; Male; Mice; Molecular Structure; Piperazines; Pyrazoles; Pyrimidines; Signal Transduction; Structure-Activity Relationship | 2008 |