Target Information
| Target General Information | Top | |||||
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| Target ID |
T87749
(Former ID: TTDR00823)
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| Target Name |
Growth/differentiation factor 8 (GDF-8)
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| Synonyms |
GDF8
Click to Show/Hide
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| Gene Name |
MSTN
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| Target Type |
Clinical trial target
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[1] | ||||
| Disease | [+] 3 Target-related Diseases | + | ||||
| 1 | Muscle disorder [ICD-11: FB32-FB3Z] | |||||
| 2 | Muscular atrophy [ICD-11: 8B61] | |||||
| 3 | Muscular dystrophy [ICD-11: 8C70] | |||||
| Function |
Acts specifically as a negative regulator of skeletal muscle growth.
Click to Show/Hide
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| BioChemical Class |
Growth factor
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| UniProt ID | ||||||
| Sequence |
MQKLQLCVYIYLFMLIVAGPVDLNENSEQKENVEKEGLCNACTWRQNTKSSRIEAIKIQI
LSKLRLETAPNISKDVIRQLLPKAPPLRELIDQYDVQRDDSSDGSLEDDDYHATTETIIT MPTESDFLMQVDGKPKCCFFKFSSKIQYNKVVKAQLWIYLRPVETPTTVFVQILRLIKPM KDGTRYTGIRSLKLDMNPGTGIWQSIDVKTVLQNWLKQPESNLGIEIKALDENGHDLAVT FPGPGEDGLNPFLEVKVTDTPKRSRRDFGLDCDEHSTESRCCRYPLTVDFEAFGWDWIIA PKRYKANYCSGECEFVFLQKYPHTHLVHQANPRGSAGPCCTPTKMSPINMLYFNGKEQII YGKIPAMVVDRCGCS Click to Show/Hide
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| 3D Structure | Click to Show 3D Structure of This Target | PDB | ||||
| HIT2.0 ID | T53ZQH | |||||
| Drugs and Modes of Action | Top | |||||
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| Clinical Trial Drug(s) | [+] 7 Clinical Trial Drugs | + | ||||
| 1 | ACE-031 | Drug Info | Phase 2 | Duchenne dystrophy | [2] | |
| 2 | AMG 745 | Drug Info | Phase 2 | Muscle atrophy | [3] | |
| 3 | Domagrozumab | Drug Info | Phase 2 | Duchenne dystrophy | [4] | |
| 4 | LY2495655 | Drug Info | Phase 2 | Disuse muscle atrophy | [5] | |
| 5 | PF-06252616 | Drug Info | Phase 2 | Muscular dystrophy | [6] | |
| 6 | SAR391786 | Drug Info | Phase 2 | Muscle atrophy | [7] | |
| 7 | Stamulumab | Drug Info | Phase 1/2 | Duchenne dystrophy | [8] | |
| Mode of Action | [+] 3 Modes of Action | + | ||||
| Inhibitor | [+] 2 Inhibitor drugs | + | ||||
| 1 | ACE-031 | Drug Info | [9] | |||
| 2 | Domagrozumab | Drug Info | [4] | |||
| Antagonist | [+] 1 Antagonist drugs | + | ||||
| 1 | AMG 745 | Drug Info | [10] | |||
| Modulator | [+] 1 Modulator drugs | + | ||||
| 1 | LY2495655 | Drug Info | [1] | |||
| Cell-based Target Expression Variations | Top | |||||
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| Cell-based Target Expression Variations | ||||||
| Different Human System Profiles of Target | Top |
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Human Similarity Proteins
of target is determined by comparing the sequence similarity of all human proteins with the target based on BLAST. The similarity proteins for a target are defined as the proteins with E-value < 0.005 and outside the protein families of the target.
A target that has fewer human similarity proteins outside its family is commonly regarded to possess a greater capacity to avoid undesired interactions and thus increase the possibility of finding successful drugs
(Brief Bioinform, 21: 649-662, 2020).
Human Pathway Affiliation
of target is determined by the life-essential pathways provided on KEGG database. The target-affiliated pathways were defined based on the following two criteria (a) the pathways of the studied target should be life-essential for both healthy individuals and patients, and (b) the studied target should occupy an upstream position in the pathways and therefore had the ability to regulate biological function.
Targets involved in a fewer pathways have greater likelihood to be successfully developed, while those associated with more human pathways increase the chance of undesirable interferences with other human processes
(Pharmacol Rev, 58: 259-279, 2006).
Biological Network Descriptors
of target is determined based on a human protein-protein interactions (PPI) network consisting of 9,309 proteins and 52,713 PPIs, which were with a high confidence score of ≥ 0.95 collected from STRING database.
The network properties of targets based on protein-protein interactions (PPIs) have been widely adopted for the assessment of target’s druggability. Proteins with high node degree tend to have a high impact on network function through multiple interactions, while proteins with high betweenness centrality are regarded to be central for communication in interaction networks and regulate the flow of signaling information
(Front Pharmacol, 9, 1245, 2018;
Curr Opin Struct Biol. 44:134-142, 2017).
Human Similarity Proteins
Human Pathway Affiliation
Biological Network Descriptors
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There is no similarity protein (E value < 0.005) for this target
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| KEGG Pathway | Pathway ID | Affiliated Target | Pathway Map |
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| Cytokine-cytokine receptor interaction | hsa04060 | Affiliated Target |
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| Class: Environmental Information Processing => Signaling molecules and interaction | Pathway Hierarchy | ||
| Degree | 10 | Degree centrality | 1.07E-03 | Betweenness centrality | 2.55E-04 |
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| Closeness centrality | 2.23E-01 | Radiality | 1.39E+01 | Clustering coefficient | 3.56E-01 |
| Neighborhood connectivity | 3.71E+01 | Topological coefficient | 1.91E-01 | Eccentricity | 12 |
| Download | Click to Download the Full PPI Network of This Target | ||||
| Chemical Structure based Activity Landscape of Target | Top |
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| Target Regulators | Top | |||||
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| Target-regulating microRNAs | ||||||
| Target Profiles in Patients | Top | |||||
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| Target Expression Profile (TEP) | ||||||
| Target Affiliated Biological Pathways | Top | |||||
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| Panther Pathway | [+] 1 Panther Pathways | + | ||||
| 1 | TGF-beta signaling pathway | |||||
| WikiPathways | [+] 1 WikiPathways | + | ||||
| 1 | Hypertrophy Model | |||||
| References | Top | |||||
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| REF 1 | Myostatin inhibitors as therapies for muscle wasting associated with cancer and other disorders. Curr Opin Support Palliat Care. 2013 November; 7(4): 352-360. | |||||
| REF 2 | ClinicalTrials.gov (NCT01099761) Study of ACE-031 in Subjects With Duchenne Muscular Dystrophy. U.S. National Institutes of Health. | |||||
| REF 3 | ClinicalTrials.gov (NCT00975104) AMG 745 in Subjects With Age-associated Muscle Loss. U.S. National Institutes of Health. | |||||
| REF 4 | Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA) | |||||
| REF 5 | ClinicalTrials.gov (NCT01505530) A Phase 2 Study of LY2495655 in Participants With Pancreatic Cancer. U.S. National Institutes of Health. | |||||
| REF 6 | ClinicalTrials.gov (NCT02310763) A Phase 2 Study to Evaluate the Safety, Efficacy, Pharmacokinetics and Pharmacodynamics of PF-06252616 in Duchenne Muscular Dystrophy. U.S. National Institutes of Health. | |||||
| REF 7 | ClinicalTrials.gov (NCT01963598) Study of the Safety and Efficacy of REGN1033 (SAR391786) in Patients With Sarcopenia. U.S. National Institutes of Health. | |||||
| REF 8 | ClinicalTrials.gov (NCT00104078) Study Evaluating MYO-029 in Adult Muscular Dystrophy. U.S. National Institutes of Health. | |||||
| REF 9 | A single ascending-dose study of muscle regulator ACE-031 in healthy volunteers. Muscle Nerve. 2013 Mar;47(3):416-23. | |||||
| REF 10 | The role of myostatin in muscle wasting: an overview. J Cachexia Sarcopenia Muscle. 2011 September; 2(3): 143-151. | |||||
| REF 11 | Myostatin (GDF-8) as a key factor linking muscle mass and bone structure. J Musculoskelet Neuronal Interact. 2010 Mar;10(1):56-63. | |||||
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