Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTEROKP4)

• DOT Name: Potassium voltage-gated channel subfamily F member 1 (KCNF1)
• Synonyms: Voltage-gated potassium channel subunit Kv5.1; kH1
• Gene Name: KCNF1
• UniProt ID: KCNF1_HUMAN
• Pfam ID: PF02214 ; PF00520
• Sequence:
  MDGSGERSLPEPGSQSSAASDDIEIVVNVGGVRQVLYGDLLSQYPETRLAELINCLAGGY
  DTIFSLCDDYDPGKREFYFDRDPDAFKCVIEVYYFGEVHMKKGICPICFKNEMDFWKVDL
  KFLDDCCKSHLSEKREELEEIARRVQLILDDLGVDAAEGRWRRCQKCVWKFLEKPESSCP
  ARVVAVLSFLLILVSSVVMCMGTIPELQVLDAEGNRVEHPTLENVETACIGWFTLEYLLR
  LFSSPNKLHFALSFMNIVDVLAILPFYVSLTLTHLGARMMELTNVQQAVQALRIMRIARI
  FKLARHSSGLQTLTYALKRSFKELGLLLMYLAVGIFVFSALGYTMEQSHPETLFKSIPQS
  FWWAIITMTTVGYGDIYPKTTLGKLNAAISFLCGVIAIALPIHPIINNFVRYYNKQRVLE
  TAAKHELELMELNSSSGGEGKTGGSRSDLDNLPPEPAGKEAPSCSSRLKLSHSDTFIPLL
  TEEKHHRTRLQSCK
• Function: Putative voltage-gated potassium channel.
• Tissue Specificity: Detected in heart, brain, liver, skeletal muscle, kidney and pancreas.
• Reactome Pathway: Voltage gated Potassium channels (R-HSA-1296072)

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 Potassium voltage-gated channel subfamily F member 1 (KCNF1).	[1]
Octanal	DMTN0OK	Investigative	Octanal increases the methylation of Potassium voltage-gated channel subfamily F member 1 (KCNF1).	[10]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Potassium voltage-gated channel subfamily F member 1 (KCNF1).	[2]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Potassium voltage-gated channel subfamily F member 1 (KCNF1).	[3]
Marinol	DM70IK5	Approved	Marinol decreases the expression of Potassium voltage-gated channel subfamily F member 1 (KCNF1).	[4]
Niclosamide	DMJAGXQ	Approved	Niclosamide increases the expression of Potassium voltage-gated channel subfamily F member 1 (KCNF1).	[5]
Diethylstilbestrol	DMN3UXQ	Approved	Diethylstilbestrol increases the expression of Potassium voltage-gated channel subfamily F member 1 (KCNF1).	[6]
Genistein	DM0JETC	Phase 2/3	Genistein increases the expression of Potassium voltage-gated channel subfamily F member 1 (KCNF1).	[6]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Potassium voltage-gated channel subfamily F member 1 (KCNF1).	[7]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Potassium voltage-gated channel subfamily F member 1 (KCNF1).	[8]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Potassium voltage-gated channel subfamily F member 1 (KCNF1).	[6]
methyl p-hydroxybenzoate	DMO58UW	Investigative	methyl p-hydroxybenzoate increases the expression of Potassium voltage-gated channel subfamily F member 1 (KCNF1).	[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] 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.
• [3] 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.
• [4] 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.
• [5] Mitochondrial Uncoupling Induces Epigenome Remodeling and Promotes Differentiation in Neuroblastoma. Cancer Res. 2023 Jan 18;83(2):181-194. doi: 10.1158/0008-5472.CAN-22-1029.
• [6] Gene expression profiling in Ishikawa cells: a fingerprint for estrogen active compounds. Toxicol Appl Pharmacol. 2009 Apr 1;236(1):85-96.
• [7] Transcriptional signature of human macrophages exposed to the environmental contaminant benzo(a)pyrene. Toxicol Sci. 2010 Apr;114(2):247-59.
• [8] Synergistic effect of JQ1 and rapamycin for treatment of human osteosarcoma. Int J Cancer. 2015 May 1;136(9):2055-64.
• [9] Comparison of the global gene expression profiles produced by methylparaben, n-butylparaben and 17beta-oestradiol in MCF7 human breast cancer cells. J Appl Toxicol. 2007 Jan-Feb;27(1):67-77. doi: 10.1002/jat.1200.
• [10] DNA Methylome Analysis of Saturated Aliphatic Aldehydes in Pulmonary Toxicity. Sci Rep. 2018 Jul 12;8(1):10497. doi: 10.1038/s41598-018-28813-z.