Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT2QLD11)

• DOT Name: Inhibin beta B chain (INHBB)
• Synonyms: Activin beta-B chain
• Gene Name: INHBB
• Related Disease:
  Adenoma
  Anorexia nervosa cachexia
  Breast cancer
  Breast carcinoma
  Breast neoplasm
  Colorectal carcinoma
  Congenital hypothyroidism
  Endometrial carcinoma
  Familial male-limited precocious puberty
  Female hypogonadism
  Hypogonadism
  Polycystic ovarian syndrome
  Split hand-foot malformation
  Carcinoma
  Kaposi sarcoma
• UniProt ID: INHBB_HUMAN
• PDB ID: 7U5O
• Pfam ID: PF00019 ; PF00688
• Sequence:
  MDGLPGRALGAACLLLLAAGWLGPEAWGSPTPPPTPAAPPPPPPPGSPGGSQDTCTSCGG
  FRRPEELGRVDGDFLEAVKRHILSRLQMRGRPNITHAVPKAAMVTALRKLHAGKVREDGR
  VEIPHLDGHASPGADGQERVSEIISFAETDGLASSRVRLYFFISNEGNQNLFVVQASLWL
  YLKLLPYVLEKGSRRKVRVKVYFQEQGHGDRWNMVEKRVDLKRSGWHTFPLTEAIQALFE
  RGERRLNLDVQCDSCQELAVVPVFVDPGEESHRPFVVVQARLGDSRHRIRKRGLECDGRT
  NLCCRQQFFIDFRLIGWNDWIIAPTGYYGNYCEGSCPAYLAGVPGSASSFHTAVVNQYRM
  RGLNPGTVNSCCIPTKLSTMSMLYFDDEYNIVKRDVPNMIVEECGCA
• Function: Inhibins and activins inhibit and activate, respectively, the secretion of follitropin by the pituitary gland. Inhibins/activins are involved in regulating a number of diverse functions such as hypothalamic and pituitary hormone secretion, gonadal hormone secretion, germ cell development and maturation, erythroid differentiation, insulin secretion, nerve cell survival, embryonic axial development or bone growth, depending on their subunit composition. Inhibins appear to oppose the functions of activins.
• KEGG Pathway:
  Cytokine-cytokine receptor interaction (hsa04060)
  TGF-beta sig.ling pathway (hsa04350)
  Sig.ling pathways regulating pluripotency of stem cells (hsa04550)
• Reactome Pathway:
  Glycoprotein hormones (R-HSA-209822)
  Antagonism of Activin by Follistatin (R-HSA-2473224)
  Signaling by Activin (R-HSA-1502540)

Molecular Interaction Atlas (MIA) of This DOT

15 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Adenoma	DIS78ZEV	Strong	Posttranslational Modification	[1]
Anorexia nervosa cachexia	DISFO5RQ	Strong	Altered Expression	[2]
Breast cancer	DIS7DPX1	Strong	Genetic Variation	[3]
Breast carcinoma	DIS2UE88	Strong	Genetic Variation	[3]
Breast neoplasm	DISNGJLM	Strong	Altered Expression	[4]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[5]
Congenital hypothyroidism	DISL5XVU	Strong	Biomarker	[6]
Endometrial carcinoma	DISXR5CY	Strong	Altered Expression	[7]
Familial male-limited precocious puberty	DISNNKVB	Strong	Biomarker	[8]
Female hypogonadism	DISWASB4	Strong	Biomarker	[9]
Hypogonadism	DISICMNI	Strong	Biomarker	[9]
Polycystic ovarian syndrome	DISZ2BNG	Strong	Biomarker	[10]
Split hand-foot malformation	DIS8PKGD	Strong	Genetic Variation	[11]
Carcinoma	DISH9F1N	moderate	Biomarker	[12]
Kaposi sarcoma	DISC1H1Z	Disputed	Genetic Variation	[13]

This DOT Affected the Regulation of Drug Effects of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Uric acid	DMA1MKT	Investigative	Inhibin beta B chain (INHBB) affects the abundance of Uric acid.	[35]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Inhibin beta B chain (INHBB).	[14]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Inhibin beta B chain (INHBB).	[15]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Inhibin beta B chain (INHBB).	[16]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Inhibin beta B chain (INHBB).	[17]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Inhibin beta B chain (INHBB).	[18]
Estradiol	DMUNTE3	Approved	Estradiol affects the expression of Inhibin beta B chain (INHBB).	[19]
Arsenic	DMTL2Y1	Approved	Arsenic affects the expression of Inhibin beta B chain (INHBB).	[20]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Inhibin beta B chain (INHBB).	[21]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Inhibin beta B chain (INHBB).	[22]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide increases the expression of Inhibin beta B chain (INHBB).	[23]
Carbamazepine	DMZOLBI	Approved	Carbamazepine decreases the expression of Inhibin beta B chain (INHBB).	[24]
Progesterone	DMUY35B	Approved	Progesterone increases the expression of Inhibin beta B chain (INHBB).	[25]
Menadione	DMSJDTY	Approved	Menadione increases the expression of Inhibin beta B chain (INHBB).	[23]
Dexamethasone	DMMWZET	Approved	Dexamethasone increases the expression of Inhibin beta B chain (INHBB).	[26]
Obeticholic acid	DM3Q1SM	Approved	Obeticholic acid increases the expression of Inhibin beta B chain (INHBB).	[27]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Inhibin beta B chain (INHBB).	[28]
Genistein	DM0JETC	Phase 2/3	Genistein decreases the expression of Inhibin beta B chain (INHBB).	[29]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of Inhibin beta B chain (INHBB).	[31]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane increases the expression of Inhibin beta B chain (INHBB).	[33]
Glyphosate	DM0AFY7	Investigative	Glyphosate decreases the expression of Inhibin beta B chain (INHBB).	[34]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Inhibin beta B chain (INHBB).	[30]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the secretion of Inhibin beta B chain (INHBB).	[32]

References

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• [27] Pharmacotoxicology of clinically-relevant concentrations of obeticholic acid in an organotypic human hepatocyte system. Toxicol In Vitro. 2017 Mar;39:93-103.
• [28] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [29] A high concentration of genistein down-regulates activin A, Smad3 and other TGF-beta pathway genes in human uterine leiomyoma cells. Exp Mol Med. 2012 Apr 30;44(4):281-92.
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