Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTP7PI9L)

• DOT Name: Bax inhibitor 1 (TMBIM6)
• Synonyms: BI-1; Testis-enhanced gene transcript protein; Transmembrane BAX inhibitor motif-containing protein 6
• Gene Name: TMBIM6
• UniProt ID: BI1_HUMAN
• Pfam ID: PF01027
• Sequence:
  MNIFDRKINFDALLKFSHITPSTQQHLKKVYASFALCMFVAAAGAYVHMVTHFIQAGLLS
  ALGSLILMIWLMATPHSHETEQKRLGLLAGFAFLTGVGLGPALEFCIAVNPSILPTAFMG
  TAMIFTCFTLSALYARRRSYLFLGGILMSALSLLLLSSLGNVFFGSIWLFQANLYVGLVV
  MCGFVLFDTQLIIEKAEHGDQDYIWHCIDLFLDFITVFRKLMMILAMNEKDKKKEKK
• Function: Suppressor of apoptosis. Modulates unfolded protein response signaling. Modulates ER calcium homeostasis by acting as a calcium-leak channel. Negatively regulates autophagy and autophagosome formation, especially during periods of nutrient deprivation, and reduces cell survival during starvation.
• Tissue Specificity: Highly abundant in testis.
• KEGG Pathway: Pathogenic Escherichia coli infection (hsa05130)

Molecular Interaction Atlas (MIA) of This DOT

11 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 Bax inhibitor 1 (TMBIM6).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Bax inhibitor 1 (TMBIM6).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Bax inhibitor 1 (TMBIM6).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Bax inhibitor 1 (TMBIM6).	[4]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Bax inhibitor 1 (TMBIM6).	[5]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Bax inhibitor 1 (TMBIM6).	[6]
Tamibarotene	DM3G74J	Phase 3	Tamibarotene affects the expression of Bax inhibitor 1 (TMBIM6).	[3]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Bax inhibitor 1 (TMBIM6).	[8]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Bax inhibitor 1 (TMBIM6).	[9]
methyl p-hydroxybenzoate	DMO58UW	Investigative	methyl p-hydroxybenzoate increases the expression of Bax inhibitor 1 (TMBIM6).	[10]
GALLICACID	DM6Y3A0	Investigative	GALLICACID increases the expression of Bax inhibitor 1 (TMBIM6).	[11]

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 Bax inhibitor 1 (TMBIM6).	[7]

References

• [1] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [2] Integrative "-Omics" analysis in primary human hepatocytes unravels persistent mechanisms of cyclosporine A-induced cholestasis. Chem Res Toxicol. 2016 Dec 19;29(12):2164-2174.
• [3] 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.
• [4] 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.
• [5] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [6] The exosome-like vesicles derived from androgen exposed-prostate stromal cells promote epithelial cells proliferation and epithelial-mesenchymal transition. Toxicol Appl Pharmacol. 2021 Jan 15;411:115384. doi: 10.1016/j.taap.2020.115384. Epub 2020 Dec 25.
• [7] 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.
• [8] 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.
• [9] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [10] Transcriptome dynamics of alternative splicing events revealed early phase of apoptosis induced by methylparaben in H1299 human lung carcinoma cells. Arch Toxicol. 2020 Jan;94(1):127-140. doi: 10.1007/s00204-019-02629-w. Epub 2019 Nov 20.
• [11] Gene expression profile analysis of gallic acid-induced cell death process. Sci Rep. 2021 Aug 18;11(1):16743. doi: 10.1038/s41598-021-96174-1.