Details of Drug Off-Target (DOT)

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

• DOT Name: SAM pointed domain-containing Ets transcription factor (SPDEF)
• Synonyms: Prostate epithelium-specific Ets transcription factor; Prostate-specific Ets; Prostate-derived Ets factor
• Gene Name: SPDEF
• UniProt ID: SPDEF_HUMAN
• PDB ID: 1YO5; 2DKX
• Pfam ID: PF00178 ; PF02198
• Sequence:
  MGSASPGLSSVSPSHLLLPPDTVSRTGLEKAAAGAVGLERRDWSPSPPATPEQGLSAFYL
  SYFDMLYPEDSSWAAKAPGASSREEPPEEPEQCPVIDSQAPAGSLDLVPGGLTLEEHSLE
  QVQSMVVGEVLKDIETACKLLNITADPMDWSPSNVQKWLLWTEHQYRLPPMGKAFQELAG
  KELCAMSEEQFRQRSPLGGDVLHAHLDIWKSAAWMKERTSPGAIHYCASTSEESWTDSEV
  DSSCSGQPIHLWQFLKELLLKPHSYGRFIRWLNKEKGIFKIEDSAQVARLWGIRKNRPAM
  NYDKLSRSIRQYYKKGIIRKPDISQRLVYQFVHPI
• Function: May function as an androgen-independent transactivator of the prostate-specific antigen (PSA) promoter. Binds to 5'-GGAT-3' DNA sequences. May play a role in the regulation of the prostate gland and/or prostate cancer development. Acts as a transcriptional activator for SERPINB5 promoter.
• Tissue Specificity: Expressed in a very restricted set of primarily hormone-regulated epithelial tissues with particularly high expression in the prostate gland. Significantly lower expression is seen in other hormone regulated tissues such as mammary gland, salivary gland, and ovary. Expressed in prostate carcinoma cells.

Molecular Interaction Atlas (MIA) 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 SAM pointed domain-containing Ets transcription factor (SPDEF).	[1]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of SAM pointed domain-containing Ets transcription factor (SPDEF).	[6]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of SAM pointed domain-containing Ets transcription factor (SPDEF).	[2]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of SAM pointed domain-containing Ets transcription factor (SPDEF).	[3]
Seocalcitol	DMKL9QO	Phase 3	Seocalcitol increases the expression of SAM pointed domain-containing Ets transcription factor (SPDEF).	[4]
Genistein	DM0JETC	Phase 2/3	Genistein decreases the expression of SAM pointed domain-containing Ets transcription factor (SPDEF).	[5]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of SAM pointed domain-containing Ets transcription factor (SPDEF).	[7]
Deguelin	DMXT7WG	Investigative	Deguelin decreases the expression of SAM pointed domain-containing Ets transcription factor (SPDEF).	[8]
Oxalic Acid	DMLN2GQ	Investigative	Oxalic Acid increases the expression of SAM pointed domain-containing Ets transcription factor (SPDEF).	[9]

References

• [1] 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.
• [2] 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.
• [3] LSD1 activates a lethal prostate cancer gene network independently of its demethylase function. Proc Natl Acad Sci U S A. 2018 May 1;115(18):E4179-E4188.
• [4] Prostate-derived Ets transcription factor as a favorable prognostic marker in ovarian cancer patients. Int J Cancer. 2008 Sep 15;123(6):1376-84. doi: 10.1002/ijc.23667.
• [5] Using DNA microarray analyses to elucidate the effects of genistein in androgen-responsive prostate cancer cells: identification of novel targets. Mol Carcinog. 2004 Oct;41(2):108-119.
• [6] 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.
• [7] CCAT1 is an enhancer-templated RNA that predicts BET sensitivity in colorectal cancer. J Clin Invest. 2016 Feb;126(2):639-52.
• [8] Neurotoxicity and underlying cellular changes of 21 mitochondrial respiratory chain inhibitors. Arch Toxicol. 2021 Feb;95(2):591-615. doi: 10.1007/s00204-020-02970-5. Epub 2021 Jan 29.
• [9] Effects of Wood Smoke Constituents on Mucin Gene Expression in Mice and Human Airway Epithelial Cells and on Nasal Epithelia of Subjects with a Susceptibility Gene Variant in Tp53. Environ Health Perspect. 2022 Jan;130(1):17010. doi: 10.1289/EHP9446. Epub 2022 Jan 24.