Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT00U3Y3)

• DOT Name: Glycoprotein hormones alpha chain (CGA)
• Synonyms: Anterior pituitary glycoprotein hormones common subunit alpha; Choriogonadotropin alpha chain; Chorionic gonadotrophin subunit alpha; CG-alpha; Follicle-stimulating hormone alpha chain; FSH-alpha; Follitropin alpha chain; Luteinizing hormone alpha chain; LSH-alpha; Lutropin alpha chain; Thyroid-stimulating hormone alpha chain; TSH-alpha; Thyrotropin alpha chain
• Gene Name: CGA
• UniProt ID: GLHA_HUMAN
• PDB ID: 1DZ7; 1E9J; 1FL7; 1HCN; 1HD4; 1HRP; 1QFW; 1XWD; 4AY9; 4MQW; 7FIG; 7FIH; 7FII; 7T9I; 7UTZ; 7XW5; 8I2G
• Pfam ID: PF00236
• Sequence:
  MDYYRKYAAIFLVTLSVFLHVLHSAPDVQDCPECTLQENPFFSQPGAPILQCMGCCFSRA
  YPTPLRSKKTMLVQKNVTSESTCCVAKSYNRVTVMGGFKVENHTACHCSTCYYHKS
• Function: Shared alpha chain of the active heterodimeric glycoprotein hormones thyrotropin/thyroid stimulating hormone/TSH, lutropin/luteinizing hormone/LH, follitropin/follicle stimulating hormone/FSH and choriogonadotropin/CG. These hormones bind specific receptors on target cells that in turn activate downstream signaling pathways.
• KEGG Pathway:
  cAMP sig.ling pathway (hsa04024)
  Neuroactive ligand-receptor interaction (hsa04080)
  GnRH sig.ling pathway (hsa04912)
  Ovarian steroidogenesis (hsa04913)
  Prolactin sig.ling pathway (hsa04917)
  Thyroid hormone synthesis (hsa04918)
  Regulation of lipolysis in adipocytes (hsa04923)
  GnRH secretion (hsa04929)
  Autoimmune thyroid disease (hsa05320)
• Reactome Pathway:
  Mineralocorticoid biosynthesis (R-HSA-193993)
  Glycoprotein hormones (R-HSA-209822)
  Thyroxine biosynthesis (R-HSA-209968)
  Hormone ligand-binding receptors (R-HSA-375281)
  G alpha (s) signalling events (R-HSA-418555)
  TFAP2 (AP-2) family regulates transcription of growth factors and their receptors (R-HSA-8866910)
  Reactions specific to the complex N-glycan synthesis pathway (R-HSA-975578)
  Androgen biosynthesis (R-HSA-193048)

Molecular Interaction Atlas (MIA) of This DOT

This DOT Affected the Regulation of Drug Effects of 5 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Estradiol	DMUNTE3	Approved	Glycoprotein hormones alpha chain (CGA) increases the abundance of Estradiol.	[18]
Testosterone	DM7HUNW	Approved	Glycoprotein hormones alpha chain (CGA) increases the secretion of Testosterone.	[19]
Progesterone	DMUY35B	Approved	Glycoprotein hormones alpha chain (CGA) increases the secretion of Progesterone.	[19]
Dinoprostone	DMTYOPD	Approved	Glycoprotein hormones alpha chain (CGA) increases the secretion of Dinoprostone.	[21]
[3H]cAMP	DMZRQU7	Investigative	Glycoprotein hormones alpha chain (CGA) increases the abundance of [3H]cAMP.	[22]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Methotrexate	DM2TEOL	Approved	Glycoprotein hormones alpha chain (CGA) affects the response to substance of Methotrexate.	[20]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Glycoprotein hormones alpha chain (CGA).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Glycoprotein hormones alpha chain (CGA).	[2]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Glycoprotein hormones alpha chain (CGA).	[3]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Glycoprotein hormones alpha chain (CGA).	[4]
Nicotine	DMWX5CO	Approved	Nicotine increases the expression of Glycoprotein hormones alpha chain (CGA).	[5]
Amphotericin B	DMTAJQE	Approved	Amphotericin B increases the expression of Glycoprotein hormones alpha chain (CGA).	[6]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Glycoprotein hormones alpha chain (CGA).	[8]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN increases the expression of Glycoprotein hormones alpha chain (CGA).	[10]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Glycoprotein hormones alpha chain (CGA).	[11]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Glycoprotein hormones alpha chain (CGA).	[12]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Glycoprotein hormones alpha chain (CGA).	[13]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde increases the expression of Glycoprotein hormones alpha chain (CGA).	[14]
Forskolin	DM6ITNG	Investigative	Forskolin increases the expression of Glycoprotein hormones alpha chain (CGA).	[15]
Taurine	DMVW7N3	Investigative	Taurine increases the expression of Glycoprotein hormones alpha chain (CGA).	[16]
Anandamide	DMCKH3P	Investigative	Anandamide decreases the expression of Glycoprotein hormones alpha chain (CGA).	[17]

3 Drug(s) Affected the Protein Interaction/Cellular Processes of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Octreotide	DMHIDCJ	Approved	Octreotide decreases the secretion of Glycoprotein hormones alpha chain (CGA).	[7]
PMID28870136-Compound-48	DMPIM9L	Patented	PMID28870136-Compound-48 increases the stability of Glycoprotein hormones alpha chain (CGA).	[9]
Butanoic acid	DMTAJP7	Investigative	Butanoic acid decreases the stability of Glycoprotein hormones alpha chain (CGA).	[9]

References

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• [2] Evaluation of a human iPSC-derived BBB model for repeated dose toxicity testing with cyclosporine A as model compound. Toxicol In Vitro. 2021 Jun;73:105112. doi: 10.1016/j.tiv.2021.105112. Epub 2021 Feb 22.
• [3] Essential role of cell cycle regulatory genes p21 and p27 expression in inhibition of breast cancer cells by arsenic trioxide. Med Oncol. 2011 Dec;28(4):1225-54.
• [4] Large-scale in silico and microarray-based identification of direct 1,25-dihydroxyvitamin D3 target genes. Mol Endocrinol. 2005 Nov;19(11):2685-95.
• [5] Characterizing the genetic basis for nicotine induced cancer development: a transcriptome sequencing study. PLoS One. 2013 Jun 18;8(6):e67252.
• [6] Differential expression of microRNAs and their predicted targets in renal cells exposed to amphotericin B and its complex with copper (II) ions. Toxicol Mech Methods. 2017 Sep;27(7):537-543. doi: 10.1080/15376516.2017.1333554. Epub 2017 Jun 8.
• [7] Treatment of thyroid-stimulating hormone-secreting adenomas with octreotide. Metabolism. 1992 Sep;41(9 Suppl 2):62-5. doi: 10.1016/0026-0495(92)90033-7.
• [8] Differentiation of human placental BeWo cells by the environmental contaminant benzo(a)pyrene. Chem Biol Interact. 2014 Mar 5;210:1-11.
• [9] Enhancement by theophylline of the butyrate-mediated induction of choriogonadotropin alpha-subunit in HeLa cells. II. Effect of both agents on mRNA turnover. Arch Biochem Biophys. 1990 Jul;280(1):95-102. doi: 10.1016/0003-9861(90)90523-2.
• [10] Cadmium induces transcription independently of intracellular calcium mobilization. PLoS One. 2011;6(6):e20542.
• [11] Bisphenol A disrupts gene expression in human placental trophoblast cells. Reprod Toxicol. 2015 Jun;53:39-44.
• [12] 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.
• [13] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [14] Transcriptome profile analysis of saturated aliphatic aldehydes reveals carbon number-specific molecules involved in pulmonary toxicity. Chem Res Toxicol. 2014 Aug 18;27(8):1362-70.
• [15] Exposure to perfluorobutane sulfonate and perfluorooctanesulfonic acid disrupts the production of angiogenesis factors and stress responses in human placental syncytiotrophoblast. Reprod Toxicol. 2020 Dec;98:269-277. doi: 10.1016/j.reprotox.2020.10.013. Epub 2020 Nov 2.
• [16] Taurine-responsive genes related to signal transduction as identified by cDNA microarray analyses of HepG2 cells. J Med Food. 2006 Spring;9(1):33-41. doi: 10.1089/jmf.2006.9.33.
• [17] Anandamide down-regulates placental transporter expression through CB2 receptor-mediated inhibition of cAMP synthesis. Pharmacol Res. 2019 Mar;141:331-342. doi: 10.1016/j.phrs.2019.01.002. Epub 2019 Jan 2.
• [18] Effect of mono-(2-ethylhexyl) phthalate on steroid production of human granulosa cells. Toxicol Appl Pharmacol. 2009 Aug 15;239(1):116-23. doi: 10.1016/j.taap.2009.05.022. Epub 2009 Jun 6.
• [19] Delayed puberty in spontaneously hypertensive rats involves a primary ovarian failure independent of the hypothalamic KiSS-1/GPR54/GnRH system. Endocrinology. 2009 Jun;150(6):2889-97. doi: 10.1210/en.2008-1381. Epub 2009 Feb 19.
• [20] Gene expression profiling of 30 cancer cell lines predicts resistance towards 11 anticancer drugs at clinically achieved concentrations. Int J Cancer. 2006 Apr 1;118(7):1699-712. doi: 10.1002/ijc.21570.
• [21] Endocrine disruptors and human reproductive failure: the in?vitro effect of phthalates on human luteal cells. Fertil Steril. 2014 Sep;102(3):831-7. doi: 10.1016/j.fertnstert.2014.05.041. Epub 2014 Jul 10.
• [22] Insufficient luteinizing hormone-induced intracellular signaling disrupts ovulation in preovulatory follicles lacking estrogen receptor-{beta}. Endocrinology. 2010 Jun;151(6):2826-34. doi: 10.1210/en.2009-1446. Epub 2010 Apr 8.