Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTTPV4NB)

• DOT Name: Krueppel-like factor 16 (KLF16)
• Synonyms: Basic transcription element-binding protein 4; BTE-binding protein 4; Novel Sp1-like zinc finger transcription factor 2; Transcription factor BTEB4; Transcription factor NSLP2
• Gene Name: KLF16
• Related Disease:
  Glioma
  Autism spectrum disorder
  Neurodevelopmental disorder
  Advanced cancer
  Gastric cancer
  Glioblastoma multiforme
  Stomach cancer
• UniProt ID: KLF16_HUMAN
• Pfam ID: PF00096
• Sequence:
  MSAAVACVDYFAADVLMAISSGAVVHRGRPGPEGAGPAAGLDVRAARREAASPGTPGPPP
  PPPAASGPGPGAAAAPHLLAASILADLRGGPGAAPGGASPASSSSAASSPSSGRAPGAAP
  SAAAKSHRCPFPDCAKAYYKSSHLKSHLRTHTGERPFACDWQGCDKKFARSDELARHHRT
  HTGEKRFSCPLCSKRFTRSDHLAKHARRHPGFHPDLLRRPGARSTSPSDSLPCSLAGSPA
  PSPAPSPAPAGL
• Function: Transcription factor that binds GC and GT boxes and displaces Sp1 and Sp3 from these sequences. Modulates dopaminergic transmission in the brain.

Molecular Interaction Atlas (MIA) of This DOT

7 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Glioma	DIS5RPEH	Strong	Biomarker	[1]
Autism spectrum disorder	DISXK8NV	moderate	Genetic Variation	[2]
Neurodevelopmental disorder	DIS372XH	moderate	Genetic Variation	[2]
Advanced cancer	DISAT1Z9	Limited	Biomarker	[3]
Gastric cancer	DISXGOUK	Limited	Biomarker	[3]
Glioblastoma multiforme	DISK8246	Limited	Altered Expression	[4]
Stomach cancer	DISKIJSX	Limited	Biomarker	[3]

3 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 16 (KLF16).	[5]
Arsenic	DMTL2Y1	Approved	Arsenic increases the methylation of Krueppel-like factor 16 (KLF16).	[11]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of Krueppel-like factor 16 (KLF16).	[15]

9 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 16 (KLF16).	[6]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Krueppel-like factor 16 (KLF16).	[7]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Krueppel-like factor 16 (KLF16).	[8]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Krueppel-like factor 16 (KLF16).	[9]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Krueppel-like factor 16 (KLF16).	[10]
Amiodarone	DMUTEX3	Phase 2/3 Trial	Amiodarone increases the expression of Krueppel-like factor 16 (KLF16).	[12]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Krueppel-like factor 16 (KLF16).	[13]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Krueppel-like factor 16 (KLF16).	[14]
UNC0379	DMD1E4J	Preclinical	UNC0379 decreases the expression of Krueppel-like factor 16 (KLF16).	[16]

References

• [1] KLF16 suppresses human glioma cell proliferation and tumourigenicity by targeting TFAM.Artif Cells Nanomed Biotechnol. 2018;46(sup1):608-615. doi: 10.1080/21691401.2018.1431654. Epub 2018 Jan 29.
• [2] Rates, distribution and implications of postzygotic mosaic mutations in autism spectrum disorder.Nat Neurosci. 2017 Sep;20(9):1217-1224. doi: 10.1038/nn.4598. Epub 2017 Jul 17.
• [3] KLF16 promotes proliferation in gastric cancer cells via regulating p21 and CDK4.Am J Transl Res. 2017 Jun 15;9(6):3027-3036. eCollection 2017.
• [4] Long noncoding RNA-RNCR3 overexpression deleteriously affects the growth of glioblastoma cells through miR-185-5p/Krppel-like factor 16 axis.J Cell Biochem. 2018 Nov;119(11):9081-9089. doi: 10.1002/jcb.27167. Epub 2018 Jun 28.
• [5] 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.
• [6] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [7] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [8] 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.
• [9] Genistein and bisphenol A exposure cause estrogen receptor 1 to bind thousands of sites in a cell type-specific manner. Genome Res. 2012 Nov;22(11):2153-62.
• [10] 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.
• [11] Epigenetic changes in individuals with arsenicosis. Chem Res Toxicol. 2011 Feb 18;24(2):165-7. doi: 10.1021/tx1004419. Epub 2011 Feb 4.
• [12] Identification by automated screening of a small molecule that selectively eliminates neural stem cells derived from hESCs but not dopamine neurons. PLoS One. 2009 Sep 23;4(9):e7155.
• [13] Label-free quantitative proteomic analysis identifies the oncogenic role of FOXA1 in BaP-transformed 16HBE cells. Toxicol Appl Pharmacol. 2020 Sep 15;403:115160. doi: 10.1016/j.taap.2020.115160. Epub 2020 Jul 25.
• [14] 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.
• [15] 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.
• [16] Epigenetic siRNA and chemical screens identify SETD8 inhibition as a therapeutic strategy for p53 activation in high-risk neuroblastoma. Cancer Cell. 2017 Jan 9;31(1):50-63.