Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT7HWCO3)

DOT Name Inhibin alpha chain (INHA)
Gene Name INHA
Related Disease
Benign prostatic hyperplasia ( )
Adenoma ( )
Adrenal cortex neoplasm ( )
Anemia ( )
Aplasia cutis congenita ( )
Brain neoplasm ( )
Carcinoma ( )
Carcinoma of esophagus ( )
Colon cancer ( )
Colon carcinoma ( )
Corpus callosum, agenesis of ( )
Drug-resistant tuberculosis ( )
Endometriosis ( )
Epithelial ovarian cancer ( )
Familial male-limited precocious puberty ( )
Hepatocellular carcinoma ( )
High blood pressure ( )
Hypogonadism ( )
Klinefelter syndrome ( )
Male infertility ( )
Neoplasm ( )
Neoplasm of testis ( )
Ovarian cancer ( )
Polycystic ovarian syndrome ( )
Pre-eclampsia ( )
Renal cell carcinoma ( )
Seminoma ( )
Synovial sarcoma ( )
Testicular cancer ( )
Tuberculosis ( )
Advanced cancer ( )
Cervical carcinoma ( )
Choriocarcinoma ( )
Endometrial carcinoma ( )
Endometrium adenocarcinoma ( )
Fetal growth restriction ( )
Hydatidiform mole ( )
Multi-drug resistant tuberculosis ( )
Adenocarcinoma ( )
Asthma ( )
Granulosa cell tumor ( )
Ovarian neoplasm ( )
Prostate cancer ( )
Prostate carcinoma ( )
Tuberous sclerosis ( )
UniProt ID
INHA_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Pfam ID
PF00019
Sequence
MVLHLLLFLLLTPQGGHSCQGLELARELVLAKVRALFLDALGPPAVTREGGDPGVRRLPR
RHALGGFTHRGSEPEEEEDVSQAILFPATDASCEDKSAARGLAQEAEEGLFRYMFRPSQH
TRSRQVTSAQLWFHTGLDRQGTAASNSSEPLLGLLALSPGGPVAVPMSLGHAPPHWAVLH
LATSALSLLTHPVLVLLLRCPLCTCSARPEATPFLVAHTRTRPPSGGERARRSTPLMSWP
WSPSALRLLQRPPEEPAAHANCHRVALNISFQELGWERWIVYPPSFIFHYCHGGCGLHIP
PNLSLPVPGAPPTPAQPYSLLPGAQPCCAALPGTMRPLHVRTTSDGGYSFKYETVPNLLT
QHCACI
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.
Tissue Specificity
Originally found in ovary (granulosa cells) and testis (Sertoli cells), but widely distributed in many tissues including brain and placenta. In adrenal cortex expression is limited to the zona reticularis and the innermost zona fasciculata in the normal gland, extending centripetally into the zona fasciculata in hyperplasia. Also found in adrenocortical tumors. Also expressed in prostate epithelium of benign prostatic hyperplasia, in regions of basal cell hyperplasia and in nonmalignant regions of high grade prostate cancer. Only circulating inhibin B is found in male, whereas circulating inhibins A and B are found in female.
KEGG Pathway
Cytokine-cytokine receptor interaction (hsa04060 )
Reactome Pathway
Signaling by BMP (R-HSA-201451 )
Glycoprotein hormones (R-HSA-209822 )
Signaling by Activin (R-HSA-1502540 )

Molecular Interaction Atlas (MIA) of This DOT

45 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Benign prostatic hyperplasia DISI3CW2 Definitive Altered Expression [1]
Adenoma DIS78ZEV Strong Altered Expression [2]
Adrenal cortex neoplasm DISO17X1 Strong Biomarker [3]
Anemia DISTVL0C Strong Biomarker [4]
Aplasia cutis congenita DISMDAYM Strong Genetic Variation [5]
Brain neoplasm DISY3EKS Strong Biomarker [6]
Carcinoma DISH9F1N Strong Biomarker [2]
Carcinoma of esophagus DISS6G4D Strong Biomarker [7]
Colon cancer DISVC52G Strong Altered Expression [8]
Colon carcinoma DISJYKUO Strong Altered Expression [8]
Corpus callosum, agenesis of DISO9P40 Strong Genetic Variation [5]
Drug-resistant tuberculosis DIS5BUFB Strong Genetic Variation [9]
Endometriosis DISX1AG8 Strong Altered Expression [10]
Epithelial ovarian cancer DIS56MH2 Strong Biomarker [11]
Familial male-limited precocious puberty DISNNKVB Strong Biomarker [12]
Hepatocellular carcinoma DIS0J828 Strong Biomarker [13]
High blood pressure DISY2OHH Strong Biomarker [14]
Hypogonadism DISICMNI Strong Biomarker [15]
Klinefelter syndrome DISOUI7W Strong Altered Expression [16]
Male infertility DISY3YZZ Strong Genetic Variation [17]
Neoplasm DISZKGEW Strong Biomarker [18]
Neoplasm of testis DISK4XHT Strong Biomarker [19]
Ovarian cancer DISZJHAP Strong Biomarker [11]
Polycystic ovarian syndrome DISZ2BNG Strong Biomarker [20]
Pre-eclampsia DISY7Q29 Strong Genetic Variation [21]
Renal cell carcinoma DISQZ2X8 Strong Altered Expression [22]
Seminoma DIS3J8LJ Strong Biomarker [19]
Synovial sarcoma DISEZJS7 Strong Genetic Variation [23]
Testicular cancer DIS6HNYO Strong Biomarker [24]
Tuberculosis DIS2YIMD Strong Genetic Variation [25]
Advanced cancer DISAT1Z9 moderate Altered Expression [8]
Cervical carcinoma DIST4S00 moderate Biomarker [26]
Choriocarcinoma DISDBVNL moderate Biomarker [27]
Endometrial carcinoma DISXR5CY moderate Altered Expression [28]
Endometrium adenocarcinoma DISY6744 moderate Altered Expression [28]
Fetal growth restriction DIS5WEJ5 moderate Biomarker [29]
Hydatidiform mole DISKNP7O moderate Biomarker [27]
Multi-drug resistant tuberculosis DIS1A2CS Disputed Biomarker [30]
Adenocarcinoma DIS3IHTY Limited Altered Expression [28]
Asthma DISW9QNS Limited Biomarker [31]
Granulosa cell tumor DISKWVAB Limited Biomarker [32]
Ovarian neoplasm DISEAFTY Limited Biomarker [32]
Prostate cancer DISF190Y Limited Altered Expression [33]
Prostate carcinoma DISMJPLE Limited Altered Expression [33]
Tuberous sclerosis DISEMUGZ Limited Biomarker [34]
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⏷ Show the Full List of 45 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
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 Inhibin alpha chain (INHA). [35]
Bisphenol A DM2ZLD7 Investigative Bisphenol A increases the methylation of Inhibin alpha chain (INHA). [46]
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14 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Acetaminophen DMUIE76 Approved Acetaminophen decreases the expression of Inhibin alpha chain (INHA). [36]
Doxorubicin DMVP5YE Approved Doxorubicin affects the expression of Inhibin alpha chain (INHA). [37]
Estradiol DMUNTE3 Approved Estradiol decreases the expression of Inhibin alpha chain (INHA). [38]
Troglitazone DM3VFPD Approved Troglitazone decreases the expression of Inhibin alpha chain (INHA). [39]
Cocaine DMSOX7I Approved Cocaine decreases the expression of Inhibin alpha chain (INHA). [40]
Testosterone Undecanoate DMZO10Y Approved Testosterone Undecanoate decreases the expression of Inhibin alpha chain (INHA). [41]
Urethane DM7NSI0 Phase 4 Urethane decreases the expression of Inhibin alpha chain (INHA). [42]
OTX-015 DMI8RG1 Phase 1/2 OTX-015 decreases the expression of Inhibin alpha chain (INHA). [43]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene increases the mutagenesis of Inhibin alpha chain (INHA). [44]
(+)-JQ1 DM1CZSJ Phase 1 (+)-JQ1 decreases the expression of Inhibin alpha chain (INHA). [43]
Mivebresib DMCPF90 Phase 1 Mivebresib decreases the expression of Inhibin alpha chain (INHA). [43]
PMID28460551-Compound-2 DM4DOUB Patented PMID28460551-Compound-2 decreases the expression of Inhibin alpha chain (INHA). [45]
Sulforaphane DMQY3L0 Investigative Sulforaphane decreases the expression of Inhibin alpha chain (INHA). [47]
Dibutyl phthalate DMEDGKO Investigative Dibutyl phthalate increases the expression of Inhibin alpha chain (INHA). [48]
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⏷ Show the Full List of 14 Drug(s)

References

1 Loss of the expression and localization of inhibin alpha-subunit in high grade prostate cancer.J Clin Endocrinol Metab. 1998 Mar;83(3):969-75. doi: 10.1210/jcem.83.3.4640.
2 Expression of inhibin alpha in adrenocortical tumours reflects the hormonal status of the neoplasm.J Endocrinol. 2000 May;165(2):223-9. doi: 10.1677/joe.0.1650223.
3 GnRH antagonist treatment of malignant adrenocortical tumors.Endocr Relat Cancer. 2019 Jan 1;26(1):103-117. doi: 10.1530/ERC-17-0399.
4 Methylation status of immune response genes promoters in cell-free DNA differs in hemodialyzed patients with diabetic nephropathy according to the intensity of anemia therapy.Blood Purif. 2013;36(3-4):280-6. doi: 10.1159/000356094. Epub 2013 Dec 20.
5 Inhibin alpha-subunit (INHA) expression in adrenocortical cancer is linked to genetic and epigenetic INHA promoter variation.PLoS One. 2014 Aug 11;9(8):e104944. doi: 10.1371/journal.pone.0104944. eCollection 2014.
6 Inhibin alpha, beta A subunit and activin type II receptor mRNAs are expressed in human brain tumors.Endocr J. 1995 Jun;42(3):307-13. doi: 10.1507/endocrj.42.307.
7 Clinical significance of the expression of activin A in esophageal carcinoma.Int J Oncol. 2003 Jan;22(1):75-80.
8 Therapeutic advantage of genetically engineered Salmonella typhimurium carrying short hairpin RNA against inhibin alpha subunit in cancer treatment.Ann Oncol. 2018 Sep 1;29(9):2010-2017. doi: 10.1093/annonc/mdy240.
9 High Prevalence of inhA Promoter Mutations among Patients with Drug-Resistant Tuberculosis in KwaZulu-Natal, South Africa.PLoS One. 2015 Sep 2;10(9):e0135003. doi: 10.1371/journal.pone.0135003. eCollection 2015.
10 Altered expression of activin, cripto, and follistatin inthe endometrium of women with endometrioma.Fertil Steril. 2011 Jun;95(7):2241-6. doi: 10.1016/j.fertnstert.2011.03.048. Epub 2011 Apr 15.
11 Molecular analysis of inhibin A and activin A subunit gene loci in epithelial ovarian cancer.Int J Gynecol Cancer. 2002 Sep-Oct;12(5):443-7. doi: 10.1046/j.1525-1438.2002.01143.x.
12 Activating mutations in the luteinizing hormone receptor gene: a human model of non-follicle-stimulating hormone-dependent inhibin production and germ cell maturation.J Clin Endocrinol Metab. 2006 Aug;91(8):3041-7. doi: 10.1210/jc.2005-2564. Epub 2006 May 9.
13 Inhibin/activin expression in human and rodent liver: subunits and B as new players in human hepatocellular carcinoma?.Br J Cancer. 2011 Apr 12;104(8):1303-12. doi: 10.1038/bjc.2011.53. Epub 2011 Mar 15.
14 [Inhibins and Activin A in hypertensive Disorders of Pregnancy and HELLP-Syndrome].Zentralbl Gynakol. 2004 Jun;126(3):148-53. doi: 10.1055/s-2004-822592.
15 Relationship of estradiol and inhibin to the follicle-stimulating hormone variability in hypergonadotropic hypogonadism or premature ovarian failure.J Clin Endocrinol Metab. 2005 Feb;90(2):826-30. doi: 10.1210/jc.2004-1319. Epub 2004 Nov 23.
16 Is the protein expression window during testicular development affected in patients at risk for stem cell loss?.Hum Reprod. 2015 Dec;30(12):2859-70. doi: 10.1093/humrep/dev238. Epub 2015 Sep 23.
17 Polymorphisms in inhibin gene promoter associated with male infertility.Gene. 2015 Apr 1;559(2):172-6. doi: 10.1016/j.gene.2015.01.041. Epub 2015 Jan 21.
18 Inhibin- gene mutations and mRNA levels in human lymphoid and myeloid leukemia cells.Int J Oncol. 2017 Apr;50(4):1403-1412. doi: 10.3892/ijo.2017.3895. Epub 2017 Mar 2.
19 Inhibin-, E-cadherin, calretinin and Ki-67 antigen in the immunohistochemical evaluation of canine and human testicular neoplasms.Folia Histochem Cytobiol. 2014;52(4):326-34. doi: 10.5603/FHC.a2014.0036. Epub 2014 Dec 16.
20 High serum concentration of total inhibin in polycystic ovary syndrome.Fertil Steril. 2008 Nov;90(5):1859-63. doi: 10.1016/j.fertnstert.2007.08.082.
21 The 769G>A variant of the inhibin-alpha gene in Korean patients with preeclampsia.J Endocrinol Invest. 2008 Aug;31(8):700-3. doi: 10.1007/BF03346418.
22 Immunoreactivity of CD10 and inhibin alpha in differentiating hemangioblastoma of central nervous system from metastatic clear cell renal cell carcinoma.Mod Pathol. 2005 Jun;18(6):788-94. doi: 10.1038/modpathol.3800351.
23 Inhibin- and synaptophysin immunoreactivity in synovial sarcoma with granular cell features.Hum Pathol. 2012 Jun;43(6):850-7. doi: 10.1016/j.humpath.2011.07.012. Epub 2011 Nov 4.
24 The inhibin/activin signalling pathway in human gonadal and adrenal cancers.Mol Hum Reprod. 2014 Dec;20(12):1223-37. doi: 10.1093/molehr/gau074. Epub 2014 Sep 1.
25 Cross-resistance of isoniazid, para-aminosalicylic acid and pasiniazid against isoniazid-resistant Mycobacterium tuberculosis isolates in China.J Glob Antimicrob Resist. 2020 Mar;20:275-281. doi: 10.1016/j.jgar.2019.08.005. Epub 2019 Aug 16.
26 Expression and secretion of inhibin and activin in normal and neoplastic uterine tissues. High levels of serum activin A in women with endometrial and cervical carcinoma.J Clin Endocrinol Metab. 1998 Apr;83(4):1194-200. doi: 10.1210/jcem.83.4.4689.
27 Immunohistochemical expression analysis of inhibin-alpha and -beta subunits in partial and complete moles, trophoblastic tumors, and endometrial decidua.Int J Gynecol Pathol. 2001 Oct;20(4):380-5. doi: 10.1097/00004347-200110000-00011.
28 Inhibin alpha-subunit and the inhibin coreceptor betaglycan are downregulated in endometrial carcinoma.Eur J Endocrinol. 2005 Feb;152(2):277-84. doi: 10.1530/eje.1.01849.
29 HIF1A and EPAS1 potentiate hypoxia-induced upregulation of inhibin alpha chain expression in human term cytotrophoblasts in vitro.Mol Hum Reprod. 2017 Mar 1;23(3):199-209. doi: 10.1093/molehr/gax002.
30 Characterisation of drug resistance-associated mutations among clinical multidrug-resistant Mycobacterium tuberculosis isolates from Hebei Province, China.J Glob Antimicrob Resist. 2019 Sep;18:168-176. doi: 10.1016/j.jgar.2019.03.012. Epub 2019 Mar 27.
31 Regulation of activin A expression in mast cells and asthma: its effect on the proliferation of human airway smooth muscle cells.J Immunol. 2003 Apr 15;170(8):4045-52. doi: 10.4049/jimmunol.170.8.4045.
32 Comparison of Inhibin Alpha Subunit and Antimllerian Hormone Immunoreactivity in Granulosa Cell and Mucinous Ovarian Tumors.Appl Immunohistochem Mol Morphol. 2017 Jan;25(1):71-77. doi: 10.1097/PAI.0000000000000251.
33 Elevated level of inhibin-alpha subunit is pro-tumourigenic and pro-metastatic and associated with extracapsular spread in advanced prostate cancer.Br J Cancer. 2009 Jun 2;100(11):1784-93. doi: 10.1038/sj.bjc.6605089. Epub 2009 May 12.
34 Vaccination with inhibin- provides effective immunotherapy against testicular stromal cell tumors.J Immunother Cancer. 2017 Apr 18;5:37. doi: 10.1186/s40425-017-0237-2. eCollection 2017.
35 Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
36 Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
37 Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
38 Molecular mechanism of action of bisphenol and bisphenol A mediated by oestrogen receptor alpha in growth and apoptosis of breast cancer cells. Br J Pharmacol. 2013 May;169(1):167-78.
39 Effects of ciglitazone and troglitazone on the proliferation of human stomach cancer cells. World J Gastroenterol. 2009 Jan 21;15(3):310-20.
40 Gene expression in human hippocampus from cocaine abusers identifies genes which regulate extracellular matrix remodeling. PLoS One. 2007 Nov 14;2(11):e1187. doi: 10.1371/journal.pone.0001187.
41 Levonorgestrel enhances spermatogenesis suppression by testosterone with greater alteration in testicular gene expression in men. Biol Reprod. 2009 Mar;80(3):484-92.
42 Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
43 Comprehensive transcriptome profiling of BET inhibitor-treated HepG2 cells. PLoS One. 2022 Apr 29;17(4):e0266966. doi: 10.1371/journal.pone.0266966. eCollection 2022.
44 Exome-wide mutation profile in benzo[a]pyrene-derived post-stasis and immortal human mammary epithelial cells. Mutat Res Genet Toxicol Environ Mutagen. 2014 Dec;775-776:48-54. doi: 10.1016/j.mrgentox.2014.10.011. Epub 2014 Nov 4.
45 Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
46 DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
47 Transcriptome and DNA methylation changes modulated by sulforaphane induce cell cycle arrest, apoptosis, DNA damage, and suppression of proliferation in human liver cancer cells. Food Chem Toxicol. 2020 Feb;136:111047. doi: 10.1016/j.fct.2019.111047. Epub 2019 Dec 12.
48 Application of oligonucleotide microarray technology to toxic occupational exposures. J Toxicol Environ Health A. 2008;71(5):315-24.