Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT4O9RQW)

• DOT Name: Krueppel-like factor 4 (KLF4)
• Synonyms: Epithelial zinc finger protein EZF; Gut-enriched krueppel-like factor
• Gene Name: KLF4
• UniProt ID: KLF4_HUMAN
• PDB ID: 6VTX
• Pfam ID: PF00096
• Sequence:
  MRQPPGESDMAVSDALLPSFSTFASGPAGREKTLRQAGAPNNRWREELSHMKRLPPVLPG
  RPYDLAAATVATDLESGGAGAACGGSNLAPLPRRETEEFNDLLDLDFILSNSLTHPPESV
  AATVSSSASASSSSSPSSSGPASAPSTCSFTYPIRAGNDPGVAPGGTGGGLLYGRESAPP
  PTAPFNLADINDVSPSGGFVAELLRPELDPVYIPPQQPQPPGGGLMGKFVLKASLSAPGS
  EYGSPSVISVSKGSPDGSHPVVVAPYNGGPPRTCPKIKQEAVSSCTHLGAGPPLSNGHRP
  AAHDFPLGRQLPSRTTPTLGLEEVLSSRDCHPALPLPPGFHPHPGPNYPSFLPDQMQPQV
  PPLHYQGQSRGFVARAGEPCVCWPHFGTHGMMLTPPSSPLELMPPGSCMPEEPKPKRGRR
  SWPRKRTATHTCDYAGCGKTYTKSSHLKAHLRTHTGEKPYHCDWDGCGWKFARSDELTRH
  YRKHTGHRPFQCQKCDRAFSRSDHLALHMKRHF
• Function: Transcription factor; can act both as activator and as repressor. Binds the 5'-CACCC-3' core sequence. Binds to the promoter region of its own gene and can activate its own transcription. Regulates the expression of key transcription factors during embryonic development. Plays an important role in maintaining embryonic stem cells, and in preventing their differentiation. Required for establishing the barrier function of the skin and for postnatal maturation and maintenance of the ocular surface. Involved in the differentiation of epithelial cells and may also function in skeletal and kidney development. Contributes to the down-regulation of p53/TP53 transcription.
• KEGG Pathway:
  Sig.ling pathways regulating pluripotency of stem cells (hsa04550)
  Chemical carcinogenesis - receptor activation (hsa05207)
• Reactome Pathway:
  Synthesis, secretion, and deacylation of Ghrelin (R-HSA-422085)
  Transcriptional regulation of pluripotent stem cells (R-HSA-452723)
  FOXO-mediated transcription of cell cycle genes (R-HSA-9617828)
  Transcriptional regulation of white adipocyte differentiation (R-HSA-381340)

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Cyclophosphamide	DM4O2Z7	Approved	Krueppel-like factor 4 (KLF4) decreases the response to substance of Cyclophosphamide.	[36]

This DOT Affected the Regulation of Drug Effects of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Glutathione	DMAHMT9	Approved	Krueppel-like factor 4 (KLF4) increases the abundance of Glutathione.	[36]

1 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 Krueppel-like factor 4 (KLF4).	[1]

36 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 Krueppel-like factor 4 (KLF4).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Krueppel-like factor 4 (KLF4).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Krueppel-like factor 4 (KLF4).	[4]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Krueppel-like factor 4 (KLF4).	[5]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Krueppel-like factor 4 (KLF4).	[6]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Krueppel-like factor 4 (KLF4).	[7]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Krueppel-like factor 4 (KLF4).	[8]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Krueppel-like factor 4 (KLF4).	[9]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Krueppel-like factor 4 (KLF4).	[10]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of Krueppel-like factor 4 (KLF4).	[11]
Marinol	DM70IK5	Approved	Marinol increases the expression of Krueppel-like factor 4 (KLF4).	[12]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil increases the expression of Krueppel-like factor 4 (KLF4).	[13]
Cannabidiol	DM0659E	Approved	Cannabidiol increases the expression of Krueppel-like factor 4 (KLF4).	[12]
Etoposide	DMNH3PG	Approved	Etoposide increases the expression of Krueppel-like factor 4 (KLF4).	[6]
Irinotecan	DMP6SC2	Approved	Irinotecan increases the expression of Krueppel-like factor 4 (KLF4).	[14]
Indomethacin	DMSC4A7	Approved	Indomethacin increases the expression of Krueppel-like factor 4 (KLF4).	[15]
Ethinyl estradiol	DMODJ40	Approved	Ethinyl estradiol increases the expression of Krueppel-like factor 4 (KLF4).	[16]
Oxytocin	DMDL27I	Approved	Oxytocin increases the expression of Krueppel-like factor 4 (KLF4).	[17]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Krueppel-like factor 4 (KLF4).	[18]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of Krueppel-like factor 4 (KLF4).	[19]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Krueppel-like factor 4 (KLF4).	[20]
Resveratrol	DM3RWXL	Phase 3	Resveratrol increases the expression of Krueppel-like factor 4 (KLF4).	[21]
Chlorpromazine	DMBGZI3	Phase 3 Trial	Chlorpromazine decreases the expression of Krueppel-like factor 4 (KLF4).	[22]
Napabucasin	DMDZ6Q3	Phase 3	Napabucasin decreases the expression of Krueppel-like factor 4 (KLF4).	[23]
Genistein	DM0JETC	Phase 2/3	Genistein decreases the expression of Krueppel-like factor 4 (KLF4).	[24]
Amiodarone	DMUTEX3	Phase 2/3 Trial	Amiodarone increases the expression of Krueppel-like factor 4 (KLF4).	[25]
Netoglitazone	DM8H7OA	Phase 2	Netoglitazone increases the expression of Krueppel-like factor 4 (KLF4).	[26]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Krueppel-like factor 4 (KLF4).	[27]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Krueppel-like factor 4 (KLF4).	[28]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Krueppel-like factor 4 (KLF4).	[29]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Krueppel-like factor 4 (KLF4).	[30]
Coumestrol	DM40TBU	Investigative	Coumestrol decreases the expression of Krueppel-like factor 4 (KLF4).	[31]
Nickel chloride	DMI12Y8	Investigative	Nickel chloride increases the expression of Krueppel-like factor 4 (KLF4).	[32]
geraniol	DMS3CBD	Investigative	geraniol increases the expression of Krueppel-like factor 4 (KLF4).	[33]
Manganese	DMKT129	Investigative	Manganese increases the expression of Krueppel-like factor 4 (KLF4).	[34]
Ginsenoside RG3	DMFN58T	Investigative	Ginsenoside RG3 decreases the expression of Krueppel-like factor 4 (KLF4).	[35]

References

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• [19] 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.
• [20] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [21] Resveratrol-induced apoptosis is mediated by early growth response-1, Krppel-like factor 4, and activating transcription factor 3. Cancer Prev Res (Phila). 2011 Jan;4(1):116-27. doi: 10.1158/1940-6207.CAPR-10-0218.
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• [34] Gene expression profiling of human primary astrocytes exposed to manganese chloride indicates selective effects on several functions of the cells. Neurotoxicology. 2007 May;28(3):478-89.
• [35] Ginsenoside Rg3 attenuates the osimertinib resistance by reducing the stemness of non-small cell lung cancer cells. Environ Toxicol. 2020 Jun;35(6):643-651. doi: 10.1002/tox.22899. Epub 2020 Jan 9.
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