Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTA051QG)

• DOT Name: Kelch-like protein 28 (KLHL28)
• Synonyms: BTB/POZ domain-containing protein 5
• Gene Name: KLHL28
• UniProt ID: KLH28_HUMAN
• Pfam ID: PF07707 ; PF00651 ; PF01344
• Sequence:
  MDHTSPTYMLANLTHLHSEQLLQGLNLLRQHHELCDIILRVGDVKIHAHKVVLASVSPYF
  KAMFTGNLSEKENSEVEFQCIDETALQAIVEYAYTGTVFISQDTVESLLPAANLLQIKLV
  LKECCAFLESQLDPGNCIGISRFAETYGCRDLYLAATKYICQNFEAVCQTEEFFELTHAD
  LDEIVSNDCLNVATEETVFYALESWIKYDVQERQKYLAQLLNSVRLPLLSVKFLTRLYEA
  NHLIRDDRTCKHLLNEALKYHFMPEHRLSHQTVLMTRPRCAPKVLCAVGGKSGLFACLDS
  VEMYFPQNDSWIGLAPLNIPRYEFGICVLDQKVYVIGGIATNVRPGVTIRKHENSVECWN
  PDTNTWTSLERMNESRSTLGVVVLAGELYALGGYDGQSYLQSVEKYIPKIRKWQPVAPMT
  TTRSCFAAAVLDGMIYAIGGYGPAHMNSVERYDPSKDSWEMVASMADKRIHFGVGVMLGF
  IFVVGGHNGVSHLSSIERYDPHQNQWTVCRPMKEPRTGVGAAVIDNYLYVVGGHSGSSYL
  NTVQKYDPISDTWLDSAGMIYCRCNFGLTAL

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 decreases the methylation of Kelch-like protein 28 (KLHL28).	[1]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Kelch-like protein 28 (KLHL28).	[9]

11 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 Kelch-like protein 28 (KLHL28).	[2]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Kelch-like protein 28 (KLHL28).	[3]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Kelch-like protein 28 (KLHL28).	[4]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Kelch-like protein 28 (KLHL28).	[5]
Demecolcine	DMCZQGK	Approved	Demecolcine increases the expression of Kelch-like protein 28 (KLHL28).	[6]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Kelch-like protein 28 (KLHL28).	[7]
Amiodarone	DMUTEX3	Phase 2/3 Trial	Amiodarone increases the expression of Kelch-like protein 28 (KLHL28).	[8]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of Kelch-like protein 28 (KLHL28).	[10]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Kelch-like protein 28 (KLHL28).	[6]
methyl p-hydroxybenzoate	DMO58UW	Investigative	methyl p-hydroxybenzoate increases the expression of Kelch-like protein 28 (KLHL28).	[11]
QUERCITRIN	DM1DH96	Investigative	QUERCITRIN increases the expression of Kelch-like protein 28 (KLHL28).	[12]

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] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [3] 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.
• [4] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [5] The exosome-like vesicles derived from androgen exposed-prostate stromal cells promote epithelial cells proliferation and epithelial-mesenchymal transition. Toxicol Appl Pharmacol. 2021 Jan 15;411:115384. doi: 10.1016/j.taap.2020.115384. Epub 2020 Dec 25.
• [6] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [7] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [8] 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.
• [9] 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.
• [10] A trichostatin A expression signature identified by TempO-Seq targeted whole transcriptome profiling. PLoS One. 2017 May 25;12(5):e0178302. doi: 10.1371/journal.pone.0178302. eCollection 2017.
• [11] Transcriptome dynamics of alternative splicing events revealed early phase of apoptosis induced by methylparaben in H1299 human lung carcinoma cells. Arch Toxicol. 2020 Jan;94(1):127-140. doi: 10.1007/s00204-019-02629-w. Epub 2019 Nov 20.
• [12] Molecular mechanisms of quercitrin-induced apoptosis in non-small cell lung cancer. Arch Med Res. 2014 Aug;45(6):445-54.