myostatin   Click here for help

GtoPdb Ligand ID: 5025

Synonyms: GDF-8 | GDF8 | growth/differentiation factor 8
Compound class: Endogenous peptide in human, mouse or rat
Comment: Myostatin, is a type II activin receptor ACVR2B agonist. Myostatin-induced ACVR2B activation leads to SMAD pathway signalling.
Inhibition of Myostatin/ACVR2B signalling is a mechanistic target for the development of drugs to combat muscle wasting conditions. We list three clinical stage anti-myostatin monoclonal antibodies (mAbs) in the 'Biological activity' tab for this ligand. In addition to mAbs, alternative protein scaffolds are being investigated to produce anti-myostatin activity similar to mAbs but with simpler, single-domain structures and no disulfide bonds. One such example is talditercept alfa (RO7239361, BMS-986089), which is a fusion protein that derives myostatin-binding from a modified human fibronectin domain F10. Talditercept alfa has advanced to Phase 1/2 evaluation to reduce muscle atrophy in boys with Duchenne muscular dystrophy (NCT02515669). Talditercept alfa is an example of so-called 'Adnectin' protein therapeutics that are being developed as an alternative to antigen receptors (antibodies) [5].
Species: Human
Natural/Endogenous Targets
Target
activin A receptor type 2A
activin A receptor type 2B
Selectivity at ligand targets
Key to terms and symbols Click column headers to sort
Target Sp. Type Action Value Parameter Concentration range (M) Reference
landogrozumab Primary target of this compound Hs Antibody Binding 11.9 pKd - 1
⤷ pKd 11.9 (Kd 1.39x10-12 M) [1]
Description: Measured using the Sapidyne KINEXA assay.
Other ligands which bind to or alter the activity of this ligand
Key to terms and symbols Click column headers to sort
Ligand Sp. Type Action Value Parameter Concentration range (M) Reference
domagrozumab Peptide Primary target of this compound Hs Antibody Binding 11.6 pKd - 6
⤷ pKd 11.6 (Kd 2.59x10-12 M) [6]
trevogrumab Peptide Primary target of this compound Hs Antibody Binding 10.6 pKd - 4
⤷ pKd 10.6 (Kd 2.4x10-11 M) [4]
luspatercept Peptide Approved drug Hs Fusion protein Binding 9.7 pKd - 7
⤷ pKd 9.7 (Kd 2x10-10 M) [7]
Description: Binding to GDF8 determined by surface plasmon resonance (SPR).
apitegromab Peptide Hs Antibody Binding >9.0 pKd - 2
⤷ pKd >9.0 (Kd <1x10-9 M) [2]
sotatercept Peptide Hs Fusion protein Binding - - - 3
⤷ [3]