Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTQ5F1D1)

• DOT Name: Ribosome biogenesis protein BRX1 homolog (BRIX1)
• Synonyms: Brix domain-containing protein 2
• Gene Name: BRIX1
• UniProt ID: BRX1_HUMAN
• PDB ID: 8FKP; 8FKQ; 8FKR; 8FKS; 8FKT; 8FKU; 8FKV; 8FKW; 8FKX; 8FKY
• Pfam ID: PF04427
• Sequence:
  MAATKRKRRGGFAVQAKKPKRNEIDAEPPAKRHATAEEVEEEERDRIPGPVCKGKWKNKE
  RILIFSSRGINFRTRHLMQDLRMLMPHSKADTKMDRKDKLFVINEVCEMKNCNKCIYFEA
  KKKQDLYMWLSNSPHGPSAKFLVQNIHTLAELKMTGNCLKGSRPLLSFDPAFDELPHYAL
  LKELLIQIFSTPRYHPKSQPFVDHVFTFTILDNRIWFRNFQIIEEDAALVEIGPRFVLNL
  IKIFQGSFGGPTLYENPHYQSPNMHRRVIRSITAAKYREKQQVKDVQKLRKKEPKTLLPH
  DPTADVFVTPAEEKPIEIQWVKPEPKVDLKARKKRIYKRQRKMKQRMDSGKTK
• Function: Required for biogenesis of the 60S ribosomal subunit.

Molecular Interaction Atlas (MIA) of This DOT

13 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 Ribosome biogenesis protein BRX1 homolog (BRIX1).	[1]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Ribosome biogenesis protein BRX1 homolog (BRIX1).	[2]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Ribosome biogenesis protein BRX1 homolog (BRIX1).	[3]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Ribosome biogenesis protein BRX1 homolog (BRIX1).	[4]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Ribosome biogenesis protein BRX1 homolog (BRIX1).	[5]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Ribosome biogenesis protein BRX1 homolog (BRIX1).	[5]
Progesterone	DMUY35B	Approved	Progesterone decreases the expression of Ribosome biogenesis protein BRX1 homolog (BRIX1).	[6]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil decreases the expression of Ribosome biogenesis protein BRX1 homolog (BRIX1).	[7]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Ribosome biogenesis protein BRX1 homolog (BRIX1).	[8]
GSK2110183	DMZHB37	Phase 2	GSK2110183 decreases the expression of Ribosome biogenesis protein BRX1 homolog (BRIX1).	[9]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Ribosome biogenesis protein BRX1 homolog (BRIX1).	[10]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Ribosome biogenesis protein BRX1 homolog (BRIX1).	[12]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of Ribosome biogenesis protein BRX1 homolog (BRIX1).	[13]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
TAK-243	DM4GKV2	Phase 1	TAK-243 increases the sumoylation of Ribosome biogenesis protein BRX1 homolog (BRIX1).	[11]
Coumarin	DM0N8ZM	Investigative	Coumarin increases the phosphorylation of Ribosome biogenesis protein BRX1 homolog (BRIX1).	[14]

References

• [1] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [2] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [3] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [4] 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.
• [5] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [6] Gene expression in endometrial cancer cells (Ishikawa) after short time high dose exposure to progesterone. Steroids. 2008 Jan;73(1):116-28.
• [7] Pharmacogenomic identification of novel determinants of response to chemotherapy in colon cancer. Cancer Res. 2006 Mar 1;66(5):2765-77.
• [8] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [9] Novel ATP-competitive Akt inhibitor afuresertib suppresses the proliferation of malignant pleural mesothelioma cells. Cancer Med. 2017 Nov;6(11):2646-2659. doi: 10.1002/cam4.1179. Epub 2017 Sep 27.
• [10] Targeting MYCN in neuroblastoma by BET bromodomain inhibition. Cancer Discov. 2013 Mar;3(3):308-23.
• [11] Inhibiting ubiquitination causes an accumulation of SUMOylated newly synthesized nuclear proteins at PML bodies. J Biol Chem. 2019 Oct 18;294(42):15218-15234. doi: 10.1074/jbc.RA119.009147. Epub 2019 Jul 8.
• [12] Bisphenol A and bisphenol S induce distinct transcriptional profiles in differentiating human primary preadipocytes. PLoS One. 2016 Sep 29;11(9):e0163318.
• [13] A trichostatin A expression signature identified by TempO-Seq targeted whole transcriptome profiling. PLoS One. 2017 May 25;12(5):e0178302. doi: 10.1371/journal.pone.0178302. eCollection 2017.
• [14] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.