Review Article

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

Table 1

Examples of engineered BMP pathway activators.

CategoryEngineered versionModification(s)Reference(s)

BMP2-basedB2A (B2A2-K-NS)BMP2-based peptide with heparin-binding domain that augments activity of BMP2 but has no signaling ability alone[5459, 151]
BMP2-L51PBMP2 mutant that augments activity of BMP2 but has no signaling ability alone[5153]
BMP2_108BMP2-based peptide; mimics activity of BMP2[20]
mBMPBMP2-based peptide with mineral-binding domain; mimics activity of BMP2[21]
OPDBMP2-based peptide; mimics or presumed to mimic activity of BMP2[22]
P1BMP2-based peptide; mimics or presumed to mimic activity of BMP2 [23]
P2BMP2-based peptide; mimics or presumed to mimic activity of BMP2
P24BMP2-based peptide; mimics or presumed to mimic activity of BMP2[24, 25]
PEP7BMP2-based peptide; mimics or presumed to mimic activity of BMP2[26]
UnnamedBMP2-based peptide; mimics or presumed to mimic activity of BMP2[2734]

BMP2/Activin A chimeraeAB204Segmental-chimera of BMP2 and Activin A with enhanced activity over BMP2; Noggin resistant[35, 4246]
AB204-I103YVariant of AB204; enhanced activity over BMP2 and AB204[42]
AB211Segmental-chimera of BMP2 and Activin A with enhanced activity over BMP2; Noggin resistant[35]
AB215Segmental-chimera of BMP2 and Activin A with enhanced activity over BMP2; Noggin resistant[35, 47]

BMP2/BMP9 chimeraBB29Segmental-chimera of BMP2 and BMP9 with enhanced folding when produced in E. coli[35]

BMP6/BMP7 chimera80-1Segmental-chimera of BMP6 and BMP7 with reduced Noggin binding when compared to BMP7[48]

BMP7-basedBMP7-E60KBMP6-informed mutant with reduced Noggin binding[48]
THR-123BMP7-based peptide[36]
UnnamedBMP7-based peptide; mimics activity of BMP7[27]

BMP9-basedMB109BMP9-based peptide optimized for production in E. coli[37]
pBMP9BMP9-based peptide with enhanced activity over BMP9[3840]
SpBMP9BMP9-based peptide with enhanced activity over BMP9[40]
UnnamedBMP9-based peptide; mimics activity of BMP9[27]

GDF5-basedGDF5-S94NNaturally-occurring mutant with enhanced activity due to decreased inhibition by Noggin[48]
GDF5-N445KNaturally-occurring mutant with enhanced activity due to decreased inhibition by Noggin[49]
GDF5-N445TNaturally-occurring mutant with enhanced activity due to decreased inhibition by Noggin[49, 50]
GDF5-V453/V456BMP2-informed variant of GDF5; enhanced activity over GDF5 and BMP2[152, 153]

HeterodimersBMP2/6Heterodimer with enhanced activity over BMP2 and BMP6[60, 61]
BMP2/7Heterodimer with enhanced activity over BMP2 and BMP7[6267]
BMP4/7Heterodimer with enhanced activity over BMP4 and BMP7[6870]