Stem Cells International

Review Article

A Survey of Strategies to Modulate the Bone Morphogenetic Protein Signaling Pathway: Current and Future Perspectives

Table 4

Small molecule inhibitors of BMP Type 1 receptors and examples of their use.


Molecule	Comment(s)	Reference(s)

1LWY	Dramatically enhanced selectivity for ALK2 versus other type 1 BMP receptors (approximate order of selectivity: ALK2 > ALK3 > ALK6); greatly reduced off-target effects compared to DM and LDN	[120]

DMH1	Pan-type 1 BMP receptor inhibitor (approximate order of selectivity: ALK3 > ALK1 > ALK6 > ALK2); reduced off-target effects compared to DM and LDN	[121, 122, 201–205]

DMH2	Pan-type 1 BMP receptor inhibitor (approximate order selectivity: ALK6 > ALK3 > ALK2); notable off-target effects, including BMPR2, TGFBR2, ALK4, ALK5, AMPK, and VEGFR2	[120, 201, 206]

DMH3	Presumed pan-type 1 BMP receptor inhibitor; reduced off-target effects compared to DM and LDN	[201]

Dorsomorphin (DM)	Pan-type 1 BMP receptor inhibitor (approximate order of selectivity: ALK2 > ALK3 > ALK1 > ALK6); notable off-target effects, including BMPR2, ACVR2A, ACVR2B, TGFBR2, ALK5, AMPK, VEGFR2, and PDGFRβ	[114, 121, 122, 124, 201, 202, 207–215]

K02288	Modestly enhanced selectivity for ALK1 and ALK2 versus other type 1 BMP receptors (approximate order of selectivity: ALK2 > ALK1 > ALK6 > ALK3); reduced off-target effects compared to DM and LDN	[121, 216, 217]

LDN-193189 (LDN)	Pan-type 1 BMP receptor inhibitor (approximate order of selectivity: ALK1~ALK2 > ALK3 > ALK6); notable off-target effects, including BMPR2, ACVR2A, ACVR2B, TGFBR2, ALK5, AMPK, VEGFR2, and PDGFRβ	[120–122, 124, 185, 191, 207–209, 216, 218–227]

LDN-212854	Significantly enhanced selectivity for ALK1 and ALK2 versus other type 1 BMP receptors (approximate order of selectivity: ALK2 > ALK1 > ALK3); reduced off-target effects compared to DM and LDN	[121]

LDN-214117	Dramatically enhanced selectivity for ALK2 versus other type 1 BMP receptors (approximate order of selectivity: ALK1, ALK2 > ALK3); greatly reduced off-target effects compared to DM and LDN	[123]

ML-347	Dramatically enhanced selectivity for ALK1 and ALK2 versus other type 1 BMP receptors (approximate order of selectivity: ALK2 > ALK1 ≫ ALK3); reduced off-target effects compared to DM and LDN	[122, 228]

VU5350	Pan-type 1 BMP receptor inhibitor (approximate order selectivity: ALK3 > ALK2 > ALK6); notable off-target effects, including BMPR2, TGFBR2, AMPK, and VEGFR2	[120]