Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT1DL3FY)

• DOT Name: Kelch-like protein 35 (KLHL35)
• Gene Name: KLHL35
• Related Disease:
  Abdominal aortic aneurysm
  Clear cell renal carcinoma
  Hepatocellular carcinoma
  Neoplasm
  Renal cell carcinoma
• UniProt ID: KLH35_HUMAN
• Pfam ID: PF07707 ; PF00651 ; PF01344
• Sequence:
  MRQGHAPEESEPGCEAPCAGPCHAQRVLQALNAYRRSGTLTDVVLRAGGRDFPCHRAALS
  AGSAYFRSLFAAGRPERGPAVVPVVPVAPEAPGTSPAGAAAALAVVLDYVYGAGVRLRAE
  DEAAAVLALAERLGVAGLREACVRFLEGRLRAANSLALRRVAAAFSLAPLAERCGRVLRQ
  AFAEVARHADFLELAPDEVVALLADPALGVAREEAVFEAAMRWVRHDAPARRGQLRRLLE
  HVRLPLLAPAYFLEKVEADELLQACGECRPLLLEARACFILGREAGALRTRPRRFMDLAE
  VIVVIGGCDRKGLLKLPFADAYHPESQRWTPLPSLPGYTRSEFAACALRNDVYVSGGHIN
  SHDVWMFSSHLHTWIKVASLHKGRWRHKMAVVQGQLFAVGGFDGLRRLHSVERYDPFSNT
  WAAAAPLPEAVSSAAVASCAGKLFVIGGARQGGVNTDKVQCFDPKEDRWSLRSPAPFSQR
  CLEAVSLEDTIYVMGGLMSKIFTYDPGTDVWGEAAVLPSPVESCGVTVCDGKVHILGGRD
  DRGESTDKVFTFDPSSGQVEVQPSLQRCTSSHGCVTIIQSLGR

Molecular Interaction Atlas (MIA) of This DOT

5 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Abdominal aortic aneurysm	DISD06OF	Strong	Biomarker	[1]
Clear cell renal carcinoma	DISBXRFJ	Strong	Genetic Variation	[2]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[3]
Neoplasm	DISZKGEW	Strong	Genetic Variation	[2]
Renal cell carcinoma	DISQZ2X8	Strong	Genetic Variation	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate affects the expression of Kelch-like protein 35 (KLHL35).	[4]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Kelch-like protein 35 (KLHL35).	[5]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Kelch-like protein 35 (KLHL35).	[6]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Kelch-like protein 35 (KLHL35).	[7]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of Kelch-like protein 35 (KLHL35).	[6]
GSK2110183	DMZHB37	Phase 2	GSK2110183 increases the expression of Kelch-like protein 35 (KLHL35).	[8]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Kelch-like protein 35 (KLHL35).	[10]

1 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Kelch-like protein 35 (KLHL35).	[9]

References

• [1] The potential role of DNA methylation in abdominal aortic aneurysms.Int J Mol Sci. 2015 May 18;16(5):11259-75. doi: 10.3390/ijms160511259.
• [2] Genome-wide methylation analysis identifies epigenetically inactivated candidate tumour suppressor genes in renal cell carcinoma.Oncogene. 2011 Mar 24;30(12):1390-401. doi: 10.1038/onc.2010.525. Epub 2010 Dec 6.
• [3] Genome-wide analysis of DNA methylation identifies novel cancer-related genes in hepatocellular carcinoma.Tumour Biol. 2012 Oct;33(5):1307-17. doi: 10.1007/s13277-012-0378-3. Epub 2012 Mar 29.
• [4] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [5] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [6] 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.
• [7] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [8] Novel ATP-competitive Akt inhibitor afuresertib suppresses the proliferation of malignant pleural mesothelioma cells. Cancer Med. 2017 Nov;6(11):2646-2659. doi: 10.1002/cam4.1179. Epub 2017 Sep 27.
• [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] 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.