Details of Drug Off-Target (DOT)

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

• DOT Name: Hsp90 co-chaperone Cdc37-like 1 (CDC37L1)
• Synonyms: Hsp90-associating relative of Cdc37
• Gene Name: CDC37L1
• Related Disease:
  Nasopharyngeal carcinoma
  Acute myelogenous leukaemia
  Hepatocellular carcinoma
• UniProt ID: CD37L_HUMAN
• Pfam ID: PF08565
• Sequence:
  MEQPWPPPGPWSLPRAEGEAEEESDFDVFPSSPRCPQLPGGGAQMYSHGIELACQKQKEF
  VKSSVACKWNLAEAQQKLGSLALHNSESLDQEHAKAQTAVSELRQREEEWRQKEEALVQR
  EKMCLWSTDAISKDVFNKSFINQDKRKDTEDEDKSESFMQKYEQKIRHFGMLSRWDDSQR
  FLSDHPYLVCEETAKYLILWCFHLEAEKKGALMEQIAHQAVVMQFIMEMAKNCNVDPRGC
  FRLFFQKAKAEEEGYFEAFKNELEAFKSRVRLYSQSQSFQPMTVQNHVPHSGVGSIGLLE
  SLPQNPDYLQYSISTALCSLNSVVHKEDDEPKMMDTV
• Function: Co-chaperone that binds to numerous proteins and promotes their interaction with Hsp70 and Hsp90.
• Tissue Specificity: Expressed in brain, heart, kidney, liver, placenta and skeletal muscle.
• Reactome Pathway: Platelet degranulation (R-HSA-114608)

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Nasopharyngeal carcinoma	DISAOTQ0	moderate	Biomarker	[1]
Acute myelogenous leukaemia	DISCSPTN	Limited	Genetic Variation	[2]
Hepatocellular carcinoma	DIS0J828	Limited	Biomarker	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Hsp90 co-chaperone Cdc37-like 1 (CDC37L1).	[4]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Hsp90 co-chaperone Cdc37-like 1 (CDC37L1).	[5]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Hsp90 co-chaperone Cdc37-like 1 (CDC37L1).	[6]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Hsp90 co-chaperone Cdc37-like 1 (CDC37L1).	[7]
Ethanol	DMDRQZU	Approved	Ethanol decreases the expression of Hsp90 co-chaperone Cdc37-like 1 (CDC37L1).	[8]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Hsp90 co-chaperone Cdc37-like 1 (CDC37L1).	[9]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Hsp90 co-chaperone Cdc37-like 1 (CDC37L1).	[10]
Coumarin	DM0N8ZM	Investigative	Coumarin increases the phosphorylation of Hsp90 co-chaperone Cdc37-like 1 (CDC37L1).	[10]

References

• [1] Identification of candidate molecular markers of nasopharyngeal carcinoma by microarray analysis of subtracted cDNA libraries constructed by suppression subtractive hybridization.Eur J Cancer Prev. 2008 Nov;17(6):561-71. doi: 10.1097/CEJ.0b013e328305a0e8.
• [2] Genome-wide haplotype association study identify the FGFR2 gene as a risk gene for acute myeloid leukemia.Oncotarget. 2017 Jan 31;8(5):7891-7899. doi: 10.18632/oncotarget.13631.
• [3] Prognostic genes of hepatocellular carcinoma based on gene coexpression network analysis.J Cell Biochem. 2019 Jul;120(7):11616-11623. doi: 10.1002/jcb.28441. Epub 2019 Feb 18.
• [4] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [5] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [6] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [7] Reproducible chemical-induced changes in gene expression profiles in human hepatoma HepaRG cells under various experimental conditions. Toxicol In Vitro. 2009 Apr;23(3):466-75. doi: 10.1016/j.tiv.2008.12.018. Epub 2008 Dec 30.
• [8] Comparison of replicative senescence and stress-induced premature senescence combining differential display and low-density DNA arrays. FEBS Lett. 2005 Jul 4;579(17):3651-9. doi: 10.1016/j.febslet.2005.05.056.
• [9] Transcriptional signature of human macrophages exposed to the environmental contaminant benzo(a)pyrene. Toxicol Sci. 2010 Apr;114(2):247-59.
• [10] 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.