Details of Drug Off-Target (DOT)

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

DOT Name Claspin (CLSPN)
Synonyms hClaspin
Gene Name CLSPN
Related Disease
Hepatocellular carcinoma ( )
Advanced cancer ( )
Ataxia-telangiectasia ( )
Carcinoma ( )
Gastric cancer ( )
Human papillomavirus infection ( )
Neoplasm ( )
Stomach cancer ( )
Hereditary breast carcinoma ( )
Lung cancer ( )
Lung carcinoma ( )
UniProt ID
CLSPN_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
7AKO; 7PFO; 7PLO; 8B9D
Sequence
MTGEVGSEVHLEINDPNVISQEEADSPSDSGQGSYETIGPLSEGDSDEEIFVSKKLKNRK
VLQDSDSETEDTNASPEKTTYDSAEEENKENLYAGKNTKIKRIYKTVADSDESYMEKSLY
QENLEAQVKPCLELSLQSGNSTDFTTDRKSSKKHIHDKEGTAGKAKVKSKRRLEKEERKM
EKIRQLKKKETKNQEDDVEQPFNDSGCLLVDKDLFETGLEDENNSPLEDEESLESIRAAV
KNKVKKHKKKEPSLESGVHSFEEGSELSKGTTRKERKAARLSKEALKQLHSETQRLIRES
ALNLPYHMPENKTIHDFFKRKPRPTCHGNAMALLKSSKYQSSHHKEIIDTANTTEMNSDH
HSKGSEQTTGAENEVETNALPVVSKETQIITGSDESCRKDLVKNEELEIQEKQKQSDIRP
SPGDSSVLQQESNFLGNNHSEECQVGGLVAFEPHALEGEGPQNPEETDEKVEEPEQQNKS
SAVGPPEKVRRFTLDRLKQLGVDVSIKPRLGADEDSFVILEPETNRELEALKQRFWKHAN
PAAKPRAGQTVNVNVIVKDMGTDGKEELKADVVPVTLAPKKLDGASHTKPGEKLQVLKAK
LQEAMKLRRFEERQKRQALFKLDNEDGFEEEEEEEEEMTDESEEDGEEKVEKEEKEEELE
EEEEKEEEEEEEGNQETAEFLLSSEEIETKDEKEMDKENNDGSSEIGKAVGFLSVPKSLS
SDSTLLLFKDSSSKMGYFPTEEKSETDENSGKQPSKLDEDDSCSLLTKESSHNSSFELIG
STIPSYQPCNRQTGRGTSFFPTAGGFRSPSPGLFRASLVSSASKSSGKLSEPSLPIEDSQ
DLYNASPEPKTLFLGAGDFQFCLEDDTQSQLLDADGFLNVRNHRNQYQALKPRLPLASMD
ENAMDANMDELLDLCTGKFTSQAEKHLPRKSDKKENMEELLNLCSGKFTSQDASTPASSE
LNKQEKESSMGDPMEEALALCSGSFPTDKEEEDEEEEFGDFRLVSNDNEFDSDEDEHSDS
GNDLALEDHEDDDEEELLKRSEKLKRQMRLRKYLEDEAEVSGSDVGSEDEYDGEEIDEYE
EDVIDEVLPSDEELQSQIKKIHMKTMLDDDKRQLRLYQERYLADGDLHSDGPGRMRKFRW
KNIDDASQMDLFHRDSDDDQTEEQLDESEARWRKERIEREQWLRDMAQQGKITAEEEEEI
GEDSQFMILAKKVTAKALQKNASRPMVIQESKSLLRNPFEAIRPGSAQQVKTGSLLNQPK
AVLQKLAALSDHNPSAPRNSRNFVFHTLSPVKAEAAKESSKSQVKKRGPSFMTSPSPKHL
KTDDSTSGLTRSIFKYLES
Function
Required for checkpoint mediated cell cycle arrest in response to inhibition of DNA replication or to DNA damage induced by both ionizing and UV irradiation. Adapter protein which binds to BRCA1 and the checkpoint kinase CHEK1 and facilitates the ATR-dependent phosphorylation of both proteins. Also required to maintain normal rates of replication fork progression during unperturbed DNA replication. Binds directly to DNA, with particular affinity for branched or forked molecules and interacts with multiple protein components of the replisome such as the MCM2-7 complex and TIMELESS. Important for initiation of DNA replication, recruits kinase CDC7 to phosphorylate MCM2-7 components.
Reactome Pathway
Activation of ATR in response to replication stress (R-HSA-176187 )
Ub-specific processing proteases (R-HSA-5689880 )
Processing of DNA double-strand break ends (R-HSA-5693607 )
Apoptotic cleavage of cellular proteins (R-HSA-111465 )

Molecular Interaction Atlas (MIA) of This DOT

11 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Hepatocellular carcinoma DIS0J828 Definitive Biomarker [1]
Advanced cancer DISAT1Z9 Strong Biomarker [2]
Ataxia-telangiectasia DISP3EVR Strong Biomarker [3]
Carcinoma DISH9F1N Strong Biomarker [4]
Gastric cancer DISXGOUK Strong Biomarker [5]
Human papillomavirus infection DISX61LX Strong Altered Expression [4]
Neoplasm DISZKGEW Strong Biomarker [6]
Stomach cancer DISKIJSX Strong Biomarker [5]
Hereditary breast carcinoma DISAEZT5 moderate Genetic Variation [7]
Lung cancer DISCM4YA moderate Biomarker [8]
Lung carcinoma DISTR26C moderate Biomarker [8]
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⏷ Show the Full List of 11 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
17 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 Claspin (CLSPN). [9]
Acetaminophen DMUIE76 Approved Acetaminophen increases the expression of Claspin (CLSPN). [10]
Doxorubicin DMVP5YE Approved Doxorubicin decreases the expression of Claspin (CLSPN). [11]
Cisplatin DMRHGI9 Approved Cisplatin increases the expression of Claspin (CLSPN). [12]
Arsenic trioxide DM61TA4 Approved Arsenic trioxide decreases the expression of Claspin (CLSPN). [13]
Calcitriol DM8ZVJ7 Approved Calcitriol decreases the expression of Claspin (CLSPN). [14]
Testosterone DM7HUNW Approved Testosterone decreases the expression of Claspin (CLSPN). [14]
Methotrexate DM2TEOL Approved Methotrexate increases the expression of Claspin (CLSPN). [15]
Demecolcine DMCZQGK Approved Demecolcine decreases the expression of Claspin (CLSPN). [16]
Niclosamide DMJAGXQ Approved Niclosamide decreases the expression of Claspin (CLSPN). [17]
Dasatinib DMJV2EK Approved Dasatinib decreases the expression of Claspin (CLSPN). [18]
GSK2110183 DMZHB37 Phase 2 GSK2110183 decreases the expression of Claspin (CLSPN). [19]
PEITC DMOMN31 Phase 2 PEITC decreases the expression of Claspin (CLSPN). [20]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene increases the mutagenesis of Claspin (CLSPN). [21]
PMID28460551-Compound-2 DM4DOUB Patented PMID28460551-Compound-2 decreases the expression of Claspin (CLSPN). [23]
Bisphenol A DM2ZLD7 Investigative Bisphenol A decreases the expression of Claspin (CLSPN). [25]
Paraquat DMR8O3X Investigative Paraquat decreases the expression of Claspin (CLSPN). [26]
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⏷ Show the Full List of 17 Drug(s)
3 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
TAK-243 DM4GKV2 Phase 1 TAK-243 increases the sumoylation of Claspin (CLSPN). [22]
PMID28870136-Compound-52 DMFDERP Patented PMID28870136-Compound-52 affects the phosphorylation of Claspin (CLSPN). [24]
Coumarin DM0N8ZM Investigative Coumarin increases the phosphorylation of Claspin (CLSPN). [24]
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References

1 Integrated analysis of competing endogenous RNA network revealing potential prognostic biomarkers of hepatocellular carcinoma.J Cancer. 2019 Jun 2;10(14):3267-3283. doi: 10.7150/jca.29986. eCollection 2019.
2 Claspin: From replication stress and DNA damage responses to cancer therapy.Adv Protein Chem Struct Biol. 2019;115:203-246. doi: 10.1016/bs.apcsb.2018.10.007. Epub 2018 Dec 5.
3 Mechanisms of replication fork protection: a safeguard for genome stability.Crit Rev Biochem Mol Biol. 2012 May-Jun;47(3):222-35. doi: 10.3109/10409238.2012.655374. Epub 2012 Feb 11.
4 Claspin as a biomarker of human papillomavirus-related high grade lesions of uterine cervix.J Transl Med. 2012 Jun 25;10:132. doi: 10.1186/1479-5876-10-132.
5 Clinicopathological significance of claspin overexpression and its association with spheroid formation in gastric cancer.Hum Pathol. 2019 Feb;84:8-17. doi: 10.1016/j.humpath.2018.09.001. Epub 2018 Sep 18.
6 Claspin functions in cell homeostasis-A link to cancer?.DNA Repair (Amst). 2017 Nov;59:27-33. doi: 10.1016/j.dnarep.2017.09.002. Epub 2017 Sep 8.
7 Germline alterations in the CLSPN gene in breast cancer families.Cancer Lett. 2008 Mar 8;261(1):93-7. doi: 10.1016/j.canlet.2007.11.003.
8 TopBP1 and Claspin contribute to the radioresistance of lung cancer brain metastases.Mol Cancer. 2014 Sep 12;13:211. doi: 10.1186/1476-4598-13-211.
9 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.
10 Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
11 RNA sequence analysis of inducible pluripotent stem cell-derived cardiomyocytes reveals altered expression of DNA damage and cell cycle genes in response to doxorubicin. Toxicol Appl Pharmacol. 2018 Oct 1;356:44-53.
12 Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
13 Identification of transcriptome signatures and biomarkers specific for potential developmental toxicants inhibiting human neural crest cell migration. Arch Toxicol. 2016 Jan;90(1):159-80.
14 Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
15 Global molecular effects of tocilizumab therapy in rheumatoid arthritis synovium. Arthritis Rheumatol. 2014 Jan;66(1):15-23.
16 Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
17 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.
18 Dasatinib reverses cancer-associated fibroblasts (CAFs) from primary lung carcinomas to a phenotype comparable to that of normal fibroblasts. Mol Cancer. 2010 Jun 27;9:168.
19 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.
20 Phenethyl isothiocyanate alters the gene expression and the levels of protein associated with cell cycle regulation in human glioblastoma GBM 8401 cells. Environ Toxicol. 2017 Jan;32(1):176-187.
21 Exome-wide mutation profile in benzo[a]pyrene-derived post-stasis and immortal human mammary epithelial cells. Mutat Res Genet Toxicol Environ Mutagen. 2014 Dec;775-776:48-54. doi: 10.1016/j.mrgentox.2014.10.011. Epub 2014 Nov 4.
22 Inhibiting ubiquitination causes an accumulation of SUMOylated newly synthesized nuclear proteins at PML bodies. J Biol Chem. 2019 Oct 18;294(42):15218-15234. doi: 10.1074/jbc.RA119.009147. Epub 2019 Jul 8.
23 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.
24 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.
25 Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.
26 Paraquat modulates alternative pre-mRNA splicing by modifying the intracellular distribution of SRPK2. PLoS One. 2013 Apr 16;8(4):e61980. doi: 10.1371/journal.pone.0061980. Print 2013.