Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT2AH45R)

• DOT Name: Growth/differentiation factor 8 (MSTN)
• Synonyms: GDF-8; Myostatin
• Gene Name: MSTN
• Related Disease: Myostatin-related muscle hypertrophy
• UniProt ID: GDF8_HUMAN
• PDB ID: 5F3B; 5F3H; 5NTU; 5NXS; 6UMX
• Pfam ID: PF00019 ; PF00688
• Sequence:
  MQKLQLCVYIYLFMLIVAGPVDLNENSEQKENVEKEGLCNACTWRQNTKSSRIEAIKIQI
  LSKLRLETAPNISKDVIRQLLPKAPPLRELIDQYDVQRDDSSDGSLEDDDYHATTETIIT
  MPTESDFLMQVDGKPKCCFFKFSSKIQYNKVVKAQLWIYLRPVETPTTVFVQILRLIKPM
  KDGTRYTGIRSLKLDMNPGTGIWQSIDVKTVLQNWLKQPESNLGIEIKALDENGHDLAVT
  FPGPGEDGLNPFLEVKVTDTPKRSRRDFGLDCDEHSTESRCCRYPLTVDFEAFGWDWIIA
  PKRYKANYCSGECEFVFLQKYPHTHLVHQANPRGSAGPCCTPTKMSPINMLYFNGKEQII
  YGKIPAMVVDRCGCS
• Function: Acts specifically as a negative regulator of skeletal muscle growth.
• KEGG Pathway: Cytokine-cytokine receptor interaction (hsa04060)
• Reactome Pathway: FOXO-mediated transcription of cell cycle genes (R-HSA-9617828)

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Myostatin-related muscle hypertrophy	DISOL3YH	Supportive	Autosomal recessive	[1]

6 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate affects the expression of Growth/differentiation factor 8 (MSTN).	[2]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Growth/differentiation factor 8 (MSTN).	[3]
Arsenic	DMTL2Y1	Approved	Arsenic affects the expression of Growth/differentiation factor 8 (MSTN).	[4]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Growth/differentiation factor 8 (MSTN).	[5]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Growth/differentiation factor 8 (MSTN).	[6]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Growth/differentiation factor 8 (MSTN).	[7]

References

• [1] Myostatin-Related Muscle Hypertrophy C RETIRED CHAPTER, FOR HISTORICAL REFERENCE ONLY. 2005 Oct 5 [updated 2013 Jul 3]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, Gripp KW, Amemiya A, editors. GeneReviews(?) [Internet]. Seattle (WA): University of Washington, Seattle; 1993C2024.
• [2] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [3] Activin-A and myostatin response and steroid regulation in human myometrium: disruption of their signalling in uterine fibroid. J Clin Endocrinol Metab. 2011 Mar;96(3):755-65. doi: 10.1210/jc.2010-0501. Epub 2010 Dec 22.
• [4] Prenatal arsenic exposure and shifts in the newborn proteome: interindividual differences in tumor necrosis factor (TNF)-responsive signaling. Toxicol Sci. 2014 Jun;139(2):328-37. doi: 10.1093/toxsci/kfu053. Epub 2014 Mar 27.
• [5] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [6] Identification of a transcriptomic signature of food-relevant genotoxins in human HepaRG hepatocarcinoma cells. Food Chem Toxicol. 2020 Jun;140:111297. doi: 10.1016/j.fct.2020.111297. Epub 2020 Mar 28.
• [7] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.