Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTUZ4PAL)

• DOT Name: Centrosomal protein CEP57L1 (CEP57L1)
• Synonyms: Centrosomal protein 57kDa-like protein 1; Centrosomal protein of 57 kDa-related protein; Cep57R; Cep57-related protein
• Gene Name: CEP57L1
• UniProt ID: CE57L_HUMAN
• Pfam ID: PF14073 ; PF06657
• Sequence:
  MDSELMHSIVGSYHKPPERVFVPSFTQNEPSQNCHPANLEVTSPKILHSPNSQALILALK
  TLQEKIHRLELERTQAEDNLNILSREAAQYKKALENETNERNLAHQELIKQKKDISIQLS
  SAQSRCTLLEKQLEYTKRMVLNVEREKNMILEQQAQLQREKEQDQMKLYAKLEKLDVLEK
  ECFRLTTTQKTAEDKIKHLEEKLKEEEHQRKLFQDKASELQTGLEISKIIMSSVSNLKHS
  KEKKKSSKKTKCIKRRPPWQICSKFGALPFVAEKMRQHRDPHILQKPFNVTETRCLPKPS
  RTTSWCKAIPPDSEKSISICDNLSELLMAMQDELDQMSMEHQELLKQMKETESHSVCDDI
  ECELECLLKKMEIKGEQISKLKKHQDSVCKLQQKVQNSKMSEASGIQQEDSYPKGSKNIK
  NSPRKCLTDTNLFQKNSSFHPIRVHNLQMKLRRDDIMWEQ
• Function: Centrosomal protein which may be required for microtubule attachment to centrosomes.

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 Centrosomal protein CEP57L1 (CEP57L1).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the methylation of Centrosomal protein CEP57L1 (CEP57L1).	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Centrosomal protein CEP57L1 (CEP57L1).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Centrosomal protein CEP57L1 (CEP57L1).	[4]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Centrosomal protein CEP57L1 (CEP57L1).	[5]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Centrosomal protein CEP57L1 (CEP57L1).	[6]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Centrosomal protein CEP57L1 (CEP57L1).	[5]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Centrosomal protein CEP57L1 (CEP57L1).	[7]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of Centrosomal protein CEP57L1 (CEP57L1).	[8]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Centrosomal protein CEP57L1 (CEP57L1).	[9]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of Centrosomal protein CEP57L1 (CEP57L1).	[10]
GALLICACID	DM6Y3A0	Investigative	GALLICACID decreases the expression of Centrosomal protein CEP57L1 (CEP57L1).	[11]

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] Integrative "-Omics" analysis in primary human hepatocytes unravels persistent mechanisms of cyclosporine A-induced cholestasis. Chem Res Toxicol. 2016 Dec 19;29(12):2164-2174.
• [3] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [4] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [5] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [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] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [8] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [9] 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.
• [10] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.
• [11] Gene expression profile analysis of gallic acid-induced cell death process. Sci Rep. 2021 Aug 18;11(1):16743. doi: 10.1038/s41598-021-96174-1.