Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT58JBNU)

• DOT Name: cAMP-responsive element-binding protein-like 2 (CREBL2)
• Gene Name: CREBL2
• Related Disease:
  Neoplasm
  Systemic lupus erythematosus
• UniProt ID: CRBL2_HUMAN
• Pfam ID: PF07716
• Sequence:
  MDDSKVVGGKVKKPGKRGRKPAKIDLKAKLERSRQSARECRARKKLRYQYLEELVSSRER
  AICALREELEMYKQWCMAMDQGKIPSEIKALLTGEEQNKSQQNSSRHTKAGKTDANSNSW
• Function: Probable regulator of CREB1 transcriptional activity which is involved in adipose cells differentiation. May also play a regulatory role in the cell cycle. Identification in a chromosomal region frequently deleted in various cancers suggests that it might act as a tumor suppressor.

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Neoplasm	DISZKGEW	Strong	Biomarker	[1]
Systemic lupus erythematosus	DISI1SZ7	moderate	Genetic Variation	[2]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Mitoxantrone	DMM39BF	Approved	cAMP-responsive element-binding protein-like 2 (CREBL2) affects the response to substance of Mitoxantrone.	[11]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of cAMP-responsive element-binding protein-like 2 (CREBL2).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of cAMP-responsive element-binding protein-like 2 (CREBL2).	[4]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of cAMP-responsive element-binding protein-like 2 (CREBL2).	[5]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of cAMP-responsive element-binding protein-like 2 (CREBL2).	[6]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of cAMP-responsive element-binding protein-like 2 (CREBL2).	[7]
Indomethacin	DMSC4A7	Approved	Indomethacin decreases the expression of cAMP-responsive element-binding protein-like 2 (CREBL2).	[8]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of cAMP-responsive element-binding protein-like 2 (CREBL2).	[9]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of cAMP-responsive element-binding protein-like 2 (CREBL2).	[10]

References

• [1] MiR-17-92 cluster promotes hepatocarcinogenesis.Carcinogenesis. 2015 Oct;36(10):1213-22. doi: 10.1093/carcin/bgv112. Epub 2015 Aug 1.
• [2] Meta-analysis followed by replication identifies loci in or near CDKN1B, TET3, CD80, DRAM1, and ARID5B as associated with systemic lupus erythematosus in Asians.Am J Hum Genet. 2013 Jan 10;92(1):41-51. doi: 10.1016/j.ajhg.2012.11.018. Epub 2012 Dec 27.
• [3] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [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] Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
• [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] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [8] Mechanisms of indomethacin-induced alterations in the choline phospholipid metabolism of breast cancer cells. Neoplasia. 2006 Sep;8(9):758-71.
• [9] 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.
• [10] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [11] Gene expression profiling of 30 cancer cell lines predicts resistance towards 11 anticancer drugs at clinically achieved concentrations. Int J Cancer. 2006 Apr 1;118(7):1699-712. doi: 10.1002/ijc.21570.