Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTVM2SU3)

• DOT Name: Choriogonadotropin subunit beta 3 (CGB3)
• Synonyms: Choriogonadotropin subunit beta; CG-beta; Chorionic gonadotropin chain beta
• Gene Name: CGB3
• UniProt ID: CGB3_HUMAN
• PDB ID: 1HCN; 1HRP; 1QFW; 7FIG; 7FIH; 7FII
• Pfam ID: PF00007
• Sequence:
  MEMFQGLLLLLLLSMGGTWASKEPLRPRCRPINATLAVEKEGCPVCITVNTTICAGYCPT
  MTRVLQGVLPALPQVVCNYRDVRFESIRLPGCPRGVNPVVSYAVALSCQCALCRRSTTDC
  GGPKDHPLTCDDPRFQDSSSSKAPPPSLPSPSRLPGPSDTPILPQ
• Function: Beta subunit of the human chorionic gonadotropin (hCG). hCG is a complex glycoprotein composed of two glycosylated subunits alpha and beta which are non-covalently associated. The alpha subunit is identical to those in the pituitary gonadotropin hormones (LH, FSH and TSH). The beta subunits are distinct in each of the hormones and confer receptor and biological specificity. Has an essential role in pregnancy and maternal adaptation. Stimulates the ovaries to synthesize the steroids that are essential for the maintenance of pregnancy.
• Tissue Specificity: High expression in the placenta throughout pregnancy.
• Reactome Pathway:
  TFAP2 (AP-2) family regulates transcription of growth factors and their receptors (R-HSA-8866910)
  Glycoprotein hormones (R-HSA-209822)

Molecular Interaction Atlas (MIA) of This DOT

This DOT Affected the Regulation of Drug Effects of 4 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Estradiol	DMUNTE3	Approved	Choriogonadotropin subunit beta 3 (CGB3) increases the abundance of Estradiol.	[19]
Testosterone	DM7HUNW	Approved	Choriogonadotropin subunit beta 3 (CGB3) increases the abundance of Testosterone.	[20]
Progesterone	DMUY35B	Approved	Choriogonadotropin subunit beta 3 (CGB3) increases the abundance of Progesterone.	[21]
[3H]cAMP	DMZRQU7	Investigative	Choriogonadotropin subunit beta 3 (CGB3) increases the abundance of [3H]cAMP.	[23]

This DOT Affected the Biotransformations of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
PGF2alpha	DM4XAU7	Clinical trial	Choriogonadotropin subunit beta 3 (CGB3) increases the chemical synthesis of PGF2alpha.	[22]

2 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Choriogonadotropin subunit beta 3 (CGB3).	[1]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Choriogonadotropin subunit beta 3 (CGB3).	[10]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Choriogonadotropin subunit beta 3 (CGB3).	[2]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Choriogonadotropin subunit beta 3 (CGB3).	[3]
Rosiglitazone	DMILWZR	Approved	Rosiglitazone increases the expression of Choriogonadotropin subunit beta 3 (CGB3).	[5]
Alitretinoin	DMME8LH	Approved	Alitretinoin increases the expression of Choriogonadotropin subunit beta 3 (CGB3).	[5]
Pioglitazone	DMKJ485	Approved	Pioglitazone increases the expression of Choriogonadotropin subunit beta 3 (CGB3).	[7]
Resveratrol	DM3RWXL	Phase 3	Resveratrol increases the expression of Choriogonadotropin subunit beta 3 (CGB3).	[9]
Tamibarotene	DM3G74J	Phase 3	Tamibarotene decreases the expression of Choriogonadotropin subunit beta 3 (CGB3).	[2]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Choriogonadotropin subunit beta 3 (CGB3).	[11]
PMID27336223-Compound-5	DM6E50A	Patented	PMID27336223-Compound-5 increases the expression of Choriogonadotropin subunit beta 3 (CGB3).	[5]
LG100268	DM41RK2	Discontinued in Phase 1	LG100268 increases the expression of Choriogonadotropin subunit beta 3 (CGB3).	[5]
SB-431542	DM0YOXQ	Preclinical	SB-431542 increases the expression of Choriogonadotropin subunit beta 3 (CGB3).	[12]
PIRINIXIC ACID	DM82Y75	Preclinical	PIRINIXIC ACID decreases the expression of Choriogonadotropin subunit beta 3 (CGB3).	[13]
SB 203580	DMAET6F	Terminated	SB 203580 decreases the expression of Choriogonadotropin subunit beta 3 (CGB3).	[14]
Forskolin	DM6ITNG	Investigative	Forskolin increases the expression of Choriogonadotropin subunit beta 3 (CGB3).	[16]
Chlorpyrifos	DMKPUI6	Investigative	Chlorpyrifos increases the expression of Choriogonadotropin subunit beta 3 (CGB3).	[17]
Tributylstannanyl	DMHN7CB	Investigative	Tributylstannanyl increases the expression of Choriogonadotropin subunit beta 3 (CGB3).	[5]
15-deoxy-Delta(12, 14)-prostaglandin J(2)	DM8VUX3	Investigative	15-deoxy-Delta(12, 14)-prostaglandin J(2) increases the expression of Choriogonadotropin subunit beta 3 (CGB3).	[5]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Marinol	DM70IK5	Approved	Marinol decreases the secretion of Choriogonadotropin subunit beta 3 (CGB3).	[4]
Testosterone enanthate	DMB6871	Approved	Testosterone enanthate decreases the response to substance of Choriogonadotropin subunit beta 3 (CGB3).	[6]
Bezafibrate	DMZDCS0	Approved	Bezafibrate decreases the secretion of Choriogonadotropin subunit beta 3 (CGB3).	[8]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the secretion of Choriogonadotropin subunit beta 3 (CGB3).	[15]
Linoleic acid	DMDGPY9	Investigative	Linoleic acid decreases the secretion of Choriogonadotropin subunit beta 3 (CGB3).	[8]
isobutylmethylxanthine	DM46F5X	Investigative	isobutylmethylxanthine increases the response to substance of Choriogonadotropin subunit beta 3 (CGB3).	[18]

References

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• [2] Differential modulation of PI3-kinase/Akt pathway during all-trans retinoic acid- and Am80-induced HL-60 cell differentiation revealed by DNA microarray analysis. Biochem Pharmacol. 2004 Dec 1;68(11):2177-86.
• [3] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [4] The psychoactive compound of Cannabis sativa, (9)-tetrahydrocannabinol (THC) inhibits the human trophoblast cell turnover. Toxicology. 2015 Aug 6;334:94-103. doi: 10.1016/j.tox.2015.06.005. Epub 2015 Jun 9.
• [5] Trialkyltin compounds bind retinoid X receptor to alter human placental endocrine functions. Mol Endocrinol. 2005 Oct;19(10):2502-16.
• [6] Pharmacological doses of testosterone upregulated androgen receptor and 3-Beta-hydroxysteroid dehydrogenase/delta-5-delta-4 isomerase and impaired leydig cells steroidogenesis in adult rats. Toxicol Sci. 2011 Jun;121(2):397-407. doi: 10.1093/toxsci/kfr063. Epub 2011 Apr 6.
• [7] Peroxisome proliferator activated receptor gamma (PPAR-gama) ligand pioglitazone regulated gene networks in term human primary trophoblast cells. Reprod Toxicol. 2018 Oct;81:99-107.
• [8] Expression of cFABP and PPAR in trophoblast cells: effect of PPAR ligands on linoleic acid uptake and differentiation. Biochim Biophys Acta. 2005 Feb 21;1687(1-3):181-94. doi: 10.1016/j.bbalip.2004.11.017.
• [9] Effects of resveratrol on gene expression in renal cell carcinoma. Cancer Biol Ther. 2004 Sep;3(9):882-8. doi: 10.4161/cbt.3.9.1056. Epub 2004 Sep 21.
• [10] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
• [11] Inhibition of BRD4 attenuates tumor cell self-renewal and suppresses stem cell signaling in MYC driven medulloblastoma. Oncotarget. 2014 May 15;5(9):2355-71.
• [12] Activin/nodal signaling switches the terminal fate of human embryonic stem cell-derived trophoblasts. J Biol Chem. 2015 Apr 3;290(14):8834-48.
• [13] Effects of WY-14643 on peroxisomal enzyme activity and hormone secretion in immortalized human trophoblast cells. Biol Pharm Bull. 2009 Jul;32(7):1278-82. doi: 10.1248/bpb.32.1278.
• [14] Lantana macrophylla Schauer (Verbenaceae) ethanolic extract induces activation of ERK1/2 and p38 MAPKs pathway and Ca2+ imbalance in human trophoblasts derived cell lines. Food Chem Toxicol. 2012 Mar;50(3-4):1001-12. doi: 10.1016/j.fct.2011.12.021. Epub 2011 Dec 24.
• [15] Placental transport and in vitro effects of Bisphenol A. Reprod Toxicol. 2010 Aug;30(1):131-7. doi: 10.1016/j.reprotox.2010.02.007. Epub 2010 Mar 7.
• [16] Cadmium inhibits forskolin-induced differentiation of human placental BeWo cells. J Toxicol Sci. 2022;47(8):309-315. doi: 10.2131/jts.47.309.
• [17] Chlorpyrifos modifies the expression of genes involved in human placental function. Reprod Toxicol. 2012 Jun;33(3):331-8. doi: 10.1016/j.reprotox.2012.01.003. Epub 2012 Jan 21.
• [18] BLTK1 murine Leydig cells: a novel steroidogenic model for evaluating the effects of reproductive and developmental toxicants. Toxicol Sci. 2012 Jun;127(2):391-402. doi: 10.1093/toxsci/kfs121. Epub 2012 Mar 29.
• [19] Endocrine disrupting effects of herbicides and pentachlorophenol: in vitro and in vivo evidence. Environ Sci Technol. 2009 Mar 15;43(6):2144-50. doi: 10.1021/es8028928.
• [20] The inhibitory effects of manganese on steroidogenesis in rat primary Leydig cells by disrupting steroidogenic acute regulatory (StAR) protein expression. Toxicology. 2003 May 3;187(2-3):139-48. doi: 10.1016/s0300-483x(03)00063-5.
• [21] Effects of the insecticide amitraz, an alpha2-adrenergic receptor agonist, on human luteinized granulosa cells. Hum Reprod. 2005 Nov;20(11):3018-25. doi: 10.1093/humrep/dei194. Epub 2005 Aug 5.
• [22] Expression of cyclooxygenase genes and production of prostaglandins during ovulation in the ovarian follicles of Xenopus laevis. Gen Comp Endocrinol. 2008 Jun;157(2):165-73. doi: 10.1016/j.ygcen.2008.04.012. Epub 2008 May 1.
• [23] Upregulation of peripubertal rat Leydig cell steroidogenesis following 24 h in vitro and in vivo exposure to atrazine. Toxicol Sci. 2010 Nov;118(1):52-60. doi: 10.1093/toxsci/kfq227. Epub 2010 Jul 28.