Details of Drug Off-Target (DOT)

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

• DOT Name: SERTA domain-containing protein 1 (SERTAD1)
• Synonyms: CDK4-binding protein p34SEI1; SEI-1; p34(SEI-1); Transcriptional regulator interacting with the PHD-bromodomain 1; TRIP-Br1
• Gene Name: SERTAD1
• Related Disease:
  Breast cancer
  Breast carcinoma
  Colon carcinoma
  Colonic neoplasm
  Epithelial ovarian cancer
  Esophageal cancer
  Esophageal squamous cell carcinoma
  Head-neck squamous cell carcinoma
  HER2/NEU overexpressing breast cancer
  Mood disorder
  Neoplasm
  Ovarian cancer
  Ovarian neoplasm
  Prostate cancer
  Prostate carcinoma
  Squamous cell carcinoma
  Advanced cancer
  Colon cancer
• UniProt ID: SRTD1_HUMAN
• Pfam ID: PF06031
• Sequence:
  MLSKGLKRKREEEEEKEPLAVDSWWLDPGHTAVAQAPPAVASSSLFDLSVLKLHHSLQQS
  EPDLRHLVLVVNTLRRIQASMAPAAALPPVPSPPAAPSVADNLLASSDAALSASMASLLE
  DLSHIEGLSQAPQPLADEGPPGRSIGGAAPSLGALDLLGPATGCLLDDGLEGLFEDIDTS
  MYDNELWAPASEGLKPGPEDGPGKEEAPELDEAELDYLMDVLVGTQALERPPGPGR
• Function: Acts at E2F-responsive promoters as coregulator to integrate signals provided by PHD- and/or bromodomain-containing transcription factors. Stimulates E2F1/TFDP1 transcriptional activity. Renders the activity of cyclin D1/CDK4 resistant to the inhibitory effects of CDKN2A/p16INK4A.

Molecular Interaction Atlas (MIA) of This DOT

18 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Breast cancer	DIS7DPX1	Strong	Biomarker	[1]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[1]
Colon carcinoma	DISJYKUO	Strong	Posttranslational Modification	[2]
Colonic neoplasm	DISSZ04P	Strong	Biomarker	[3]
Epithelial ovarian cancer	DIS56MH2	Strong	Altered Expression	[4]
Esophageal cancer	DISGB2VN	Strong	Biomarker	[5]
Esophageal squamous cell carcinoma	DIS5N2GV	Strong	Altered Expression	[5]
Head-neck squamous cell carcinoma	DISF7P24	Strong	Biomarker	[6]
HER2/NEU overexpressing breast cancer	DISYKID5	Strong	Altered Expression	[7]
Mood disorder	DISLVMWO	Strong	Biomarker	[8]
Neoplasm	DISZKGEW	Strong	Altered Expression	[4]
Ovarian cancer	DISZJHAP	Strong	Altered Expression	[4]
Ovarian neoplasm	DISEAFTY	Strong	Altered Expression	[4]
Prostate cancer	DISF190Y	Strong	Biomarker	[9]
Prostate carcinoma	DISMJPLE	Strong	Biomarker	[9]
Squamous cell carcinoma	DISQVIFL	Strong	Biomarker	[10]
Advanced cancer	DISAT1Z9	Limited	Genetic Variation	[7]
Colon cancer	DISVC52G	Limited	Posttranslational Modification	[2]

29 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 SERTA domain-containing protein 1 (SERTAD1).	[11]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of SERTA domain-containing protein 1 (SERTAD1).	[12]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of SERTA domain-containing protein 1 (SERTAD1).	[13]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of SERTA domain-containing protein 1 (SERTAD1).	[14]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of SERTA domain-containing protein 1 (SERTAD1).	[15]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of SERTA domain-containing protein 1 (SERTAD1).	[16]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of SERTA domain-containing protein 1 (SERTAD1).	[17]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of SERTA domain-containing protein 1 (SERTAD1).	[18]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of SERTA domain-containing protein 1 (SERTAD1).	[19]
Marinol	DM70IK5	Approved	Marinol decreases the expression of SERTA domain-containing protein 1 (SERTAD1).	[20]
Zoledronate	DMIXC7G	Approved	Zoledronate decreases the expression of SERTA domain-containing protein 1 (SERTAD1).	[21]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil increases the expression of SERTA domain-containing protein 1 (SERTAD1).	[22]
Demecolcine	DMCZQGK	Approved	Demecolcine increases the expression of SERTA domain-containing protein 1 (SERTAD1).	[23]
Azathioprine	DMMZSXQ	Approved	Azathioprine increases the expression of SERTA domain-containing protein 1 (SERTAD1).	[24]
Cytarabine	DMZD5QR	Approved	Cytarabine decreases the expression of SERTA domain-containing protein 1 (SERTAD1).	[25]
Irinotecan	DMP6SC2	Approved	Irinotecan increases the expression of SERTA domain-containing protein 1 (SERTAD1).	[26]
Cidofovir	DMA13GD	Approved	Cidofovir increases the expression of SERTA domain-containing protein 1 (SERTAD1).	[21]
Ifosfamide	DMCT3I8	Approved	Ifosfamide increases the expression of SERTA domain-containing protein 1 (SERTAD1).	[21]
Clodronate	DM9Y6X7	Approved	Clodronate increases the expression of SERTA domain-containing protein 1 (SERTAD1).	[21]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of SERTA domain-containing protein 1 (SERTAD1).	[27]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of SERTA domain-containing protein 1 (SERTAD1).	[28]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of SERTA domain-containing protein 1 (SERTAD1).	[29]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of SERTA domain-containing protein 1 (SERTAD1).	[30]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN increases the expression of SERTA domain-containing protein 1 (SERTAD1).	[31]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of SERTA domain-containing protein 1 (SERTAD1).	[32]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of SERTA domain-containing protein 1 (SERTAD1).	[33]
chloropicrin	DMSGBQA	Investigative	chloropicrin increases the expression of SERTA domain-containing protein 1 (SERTAD1).	[34]
3R14S-OCHRATOXIN A	DM2KEW6	Investigative	3R14S-OCHRATOXIN A decreases the expression of SERTA domain-containing protein 1 (SERTAD1).	[35]
QUERCITRIN	DM1DH96	Investigative	QUERCITRIN increases the expression of SERTA domain-containing protein 1 (SERTAD1).	[36]

References

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• [2] p34 (SEI-1) inhibits ROS-induced cell death through suppression of ASK1.Cancer Biol Ther. 2011 Sep 1;12(5):421-6. doi: 10.4161/cbt.12.5.15972. Epub 2011 Sep 1.
• [3] Validation of biomarkers associated with 5-fluorouracil and thymidylate synthase in colorectal cancer.Oncol Rep. 2008 Jan;19(1):257-62.
• [4] SEI1 induces genomic instability by inhibiting DNA damage response in ovarian cancer.Cancer Lett. 2017 Jan 28;385:271-279. doi: 10.1016/j.canlet.2016.09.032. Epub 2016 Oct 3.
• [5] Characterization of a novel mechanism of genomic instability involving the SEI1/SET/NM23H1 pathway in esophageal cancers.Cancer Res. 2010 Jul 15;70(14):5695-705. doi: 10.1158/0008-5472.CAN-10-0392. Epub 2010 Jun 22.
• [6] Coordinated expression of cyclin-dependent kinase-4 and its regulators in human oral tumors.Anticancer Res. 2014 Jul;34(7):3285-92.
• [7] Prognostic and Clinicopathological Significance of SERTAD1 in Various Types of Cancer Risk: A Systematic Review and Retrospective Analysis.Cancers (Basel). 2019 Mar 8;11(3):337. doi: 10.3390/cancers11030337.
• [8] Inflammation and neurological disease-related genes are differentially expressed in depressed patients with mood disorders and correlate with morphometric and functional imaging abnormalities.Brain Behav Immun. 2013 Jul;31:161-71. doi: 10.1016/j.bbi.2012.10.007. Epub 2012 Oct 12.
• [9] Sertad1 promotes prostate cancer progression through binding androgen receptor ligand binding domain.Int J Cancer. 2019 Feb 1;144(3):558-568. doi: 10.1002/ijc.31877. Epub 2018 Oct 31.
• [10] Dissection of CDK4-binding and transactivation activities of p34(SEI-1) and comparison between functions of p34(SEI-1) and p16(INK4A).Biochemistry. 2005 Oct 11;44(40):13246-56. doi: 10.1021/bi0504658.
• [11] 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.
• [12] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [13] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [14] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [15] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [16] The thioxotriazole copper(II) complex A0 induces endoplasmic reticulum stress and paraptotic death in human cancer cells. J Biol Chem. 2009 Sep 4;284(36):24306-19.
• [17] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [18] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [19] Acute hypersensitivity of pluripotent testicular cancer-derived embryonal carcinoma to low-dose 5-aza deoxycytidine is associated with global DNA Damage-associated p53 activation, anti-pluripotency and DNA demethylation. PLoS One. 2012;7(12):e53003. doi: 10.1371/journal.pone.0053003. Epub 2012 Dec 27.
• [20] THC exposure of human iPSC neurons impacts genes associated with neuropsychiatric disorders. Transl Psychiatry. 2018 Apr 25;8(1):89. doi: 10.1038/s41398-018-0137-3.
• [21] Transcriptomics hit the target: monitoring of ligand-activated and stress response pathways for chemical testing. Toxicol In Vitro. 2015 Dec 25;30(1 Pt A):7-18.
• [22] Transcriptional profiling of MCF7 breast cancer cells in response to 5-Fluorouracil: relationship with cell cycle changes and apoptosis, and identification of novel targets of p53. Int J Cancer. 2006 Sep 1;119(5):1164-75.
• [23] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [24] A transcriptomics-based in vitro assay for predicting chemical genotoxicity in vivo. Carcinogenesis. 2012 Jul;33(7):1421-9.
• [25] Cytosine arabinoside induces ectoderm and inhibits mesoderm expression in human embryonic stem cells during multilineage differentiation. Br J Pharmacol. 2011 Apr;162(8):1743-56.
• [26] Gene expression profile of colon cancer cell lines treated with SN-38. Chemotherapy. 2010;56(1):17-25. doi: 10.1159/000287353. Epub 2010 Feb 24.
• [27] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [28] Transcriptional signature of human macrophages exposed to the environmental contaminant benzo(a)pyrene. Toxicol Sci. 2010 Apr;114(2):247-59.
• [29] Targeting MYCN in neuroblastoma by BET bromodomain inhibition. Cancer Discov. 2013 Mar;3(3):308-23.
• [30] 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.
• [31] Chemical stresses fail to mimic the unfolded protein response resulting from luminal load with unfolded polypeptides. J Biol Chem. 2018 Apr 13;293(15):5600-5612.
• [32] Gene expression changes in primary human nasal epithelial cells exposed to formaldehyde in vitro. Toxicol Lett. 2010 Oct 5;198(2):289-95.
• [33] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [34] Transcriptomic analysis of human primary bronchial epithelial cells after chloropicrin treatment. Chem Res Toxicol. 2015 Oct 19;28(10):1926-35.
• [35] Persistence of epigenomic effects after recovery from repeated treatment with two nephrocarcinogens. Front Genet. 2018 Dec 3;9:558.
• [36] Molecular mechanisms of quercitrin-induced apoptosis in non-small cell lung cancer. Arch Med Res. 2014 Aug;45(6):445-54.