Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTTTI622)

DOT Name Serine/threonine-protein kinase Chk1 (CHEK1)
Synonyms EC 2.7.11.1; CHK1 checkpoint homolog; Cell cycle checkpoint kinase; Checkpoint kinase-1
Gene Name CHEK1
Related Disease
Familial ovarian cancer ( )
Hereditary breast carcinoma ( )
UniProt ID
CHK1_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
1IA8 ; 1NVQ ; 1NVR ; 1NVS ; 1ZLT ; 1ZYS ; 2AYP ; 2BR1 ; 2BRB ; 2BRG ; 2BRH ; 2BRM ; 2BRN ; 2BRO ; 2C3J ; 2C3K ; 2C3L ; 2CGU ; 2CGV ; 2CGW ; 2CGX ; 2E9N ; 2E9O ; 2E9P ; 2E9U ; 2E9V ; 2GDO ; 2GHG ; 2HOG ; 2HXL ; 2HXQ ; 2HY0 ; 2QHM ; 2QHN ; 2R0U ; 2WMQ ; 2WMR ; 2WMS ; 2WMT ; 2WMU ; 2WMV ; 2WMW ; 2WMX ; 2X8D ; 2X8E ; 2X8I ; 2XEY ; 2XEZ ; 2XF0 ; 2YDI ; 2YDJ ; 2YDK ; 2YER ; 2YEX ; 2YM3 ; 2YM4 ; 2YM5 ; 2YM6 ; 2YM7 ; 2YM8 ; 2YWP ; 3F9N ; 3JVR ; 3JVS ; 3NLB ; 3OT3 ; 3OT8 ; 3PA3 ; 3PA4 ; 3PA5 ; 3TKH ; 3TKI ; 3U9N ; 4FSM ; 4FSN ; 4FSQ ; 4FSR ; 4FST ; 4FSU ; 4FSW ; 4FSY ; 4FSZ ; 4FT0 ; 4FT3 ; 4FT5 ; 4FT7 ; 4FT9 ; 4FTA ; 4FTC ; 4FTI ; 4FTJ ; 4FTK ; 4FTL ; 4FTM ; 4FTN ; 4FTO ; 4FTQ ; 4FTR ; 4FTT ; 4FTU ; 4GH2 ; 4HYH ; 4HYI ; 4JIK ; 4QYE ; 4QYF ; 4QYG ; 4QYH ; 4RVK ; 4RVL ; 4RVM ; 5DLS ; 5F4N ; 5OOP ; 5OOR ; 5OOT ; 5OP2 ; 5OP4 ; 5OP5 ; 5OP7 ; 5OPB ; 5OPR ; 5OPS ; 5OPU ; 5OPV ; 5OQ5 ; 5OQ6 ; 5OQ7 ; 5OQ8 ; 5WI2 ; 6FC8 ; 6FCF ; 6FCK ; 7AKM ; 7AKO ; 7BJD ; 7BJE ; 7BJH ; 7BJJ ; 7BJM ; 7BJO ; 7BJR ; 7BJX ; 7BK1 ; 7BK2 ; 7BK3 ; 7BKN ; 7BKO ; 7MCK ; 7SUF ; 7SUG ; 7SUH ; 7SUI ; 7SUJ ; 8E80 ; 8E81 ; 8SIV ; 8SIW ; 8SIX
EC Number
2.7.11.1
Pfam ID
PF00069
Sequence
MAVPFVEDWDLVQTLGEGAYGEVQLAVNRVTEEAVAVKIVDMKRAVDCPENIKKEICINK
MLNHENVVKFYGHRREGNIQYLFLEYCSGGELFDRIEPDIGMPEPDAQRFFHQLMAGVVY
LHGIGITHRDIKPENLLLDERDNLKISDFGLATVFRYNNRERLLNKMCGTLPYVAPELLK
RREFHAEPVDVWSCGIVLTAMLAGELPWDQPSDSCQEYSDWKEKKTYLNPWKKIDSAPLA
LLHKILVENPSARITIPDIKKDRWYNKPLKKGAKRPRVTSGGVSESPSGFSKHIQSNLDF
SPVNSASSEENVKYSSSQPEPRTGLSLWDTSPSYIDKLVQGISFSQPTCPDHMLLNSQLL
GTPGSSQNPWQRLVKRMTRFFTKLDADKSYQCLKETCEKLGYQWKKSCMNQVTISTTDRR
NNKLIFKVNLLEMDDKILVDFRLSKGDGLEFKRHFLKIKGKLIDIVSSQKIWLPAT
Function
Serine/threonine-protein kinase which is required for checkpoint-mediated cell cycle arrest and activation of DNA repair in response to the presence of DNA damage or unreplicated DNA. May also negatively regulate cell cycle progression during unperturbed cell cycles. This regulation is achieved by a number of mechanisms that together help to preserve the integrity of the genome. Recognizes the substrate consensus sequence [R-X-X-S/T]. Binds to and phosphorylates CDC25A, CDC25B and CDC25C. Phosphorylation of CDC25A at 'Ser-178' and 'Thr-507' and phosphorylation of CDC25C at 'Ser-216' creates binding sites for 14-3-3 proteins which inhibit CDC25A and CDC25C. Phosphorylation of CDC25A at 'Ser-76', 'Ser-124', 'Ser-178', 'Ser-279' and 'Ser-293' promotes proteolysis of CDC25A. Phosphorylation of CDC25A at 'Ser-76' primes the protein for subsequent phosphorylation at 'Ser-79', 'Ser-82' and 'Ser-88' by NEK11, which is required for polyubiquitination and degradation of CDCD25A. Inhibition of CDC25 leads to increased inhibitory tyrosine phosphorylation of CDK-cyclin complexes and blocks cell cycle progression. Also phosphorylates NEK6. Binds to and phosphorylates RAD51 at 'Thr-309', which promotes the release of RAD51 from BRCA2 and enhances the association of RAD51 with chromatin, thereby promoting DNA repair by homologous recombination. Phosphorylates multiple sites within the C-terminus of TP53, which promotes activation of TP53 by acetylation and promotes cell cycle arrest and suppression of cellular proliferation. Also promotes repair of DNA cross-links through phosphorylation of FANCE. Binds to and phosphorylates TLK1 at 'Ser-743', which prevents the TLK1-dependent phosphorylation of the chromatin assembly factor ASF1A. This may enhance chromatin assembly both in the presence or absence of DNA damage. May also play a role in replication fork maintenance through regulation of PCNA. May regulate the transcription of genes that regulate cell-cycle progression through the phosphorylation of histones. Phosphorylates histone H3.1 (to form H3T11ph), which leads to epigenetic inhibition of a subset of genes. May also phosphorylate RB1 to promote its interaction with the E2F family of transcription factors and subsequent cell cycle arrest. Phosphorylates SPRTN, promoting SPRTN recruitment to chromatin. Reduces replication stress and activates the G2/M checkpoint, by phosphorylating and inactivating PABIR1/FAM122A and promoting the serine/threonine-protein phosphatase 2A-mediated dephosphorylation and stabilization of WEE1 levels and activity ; [Isoform 2]: Endogenous repressor of isoform 1, interacts with, and antagonizes CHK1 to promote the S to G2/M phase transition.
Tissue Specificity Expressed ubiquitously with the most abundant expression in thymus, testis, small intestine and colon.
KEGG Pathway
Cell cycle (hsa04110 )
p53 sig.ling pathway (hsa04115 )
Cellular senescence (hsa04218 )
Human T-cell leukemia virus 1 infection (hsa05166 )
Human immunodeficiency virus 1 infection (hsa05170 )
Viral carcinogenesis (hsa05203 )
Reactome Pathway
Activation of ATR in response to replication stress (R-HSA-176187 )
Processing of DNA double-strand break ends (R-HSA-5693607 )
Presynaptic phase of homologous DNA pairing and strand exchange (R-HSA-5693616 )
TP53 Regulates Transcription of DNA Repair Genes (R-HSA-6796648 )
Regulation of TP53 Activity through Phosphorylation (R-HSA-6804756 )
G2/M DNA damage checkpoint (R-HSA-69473 )
Ubiquitin Mediated Degradation of Phosphorylated Cdc25A (R-HSA-69601 )
Chk1/Chk2(Cds1) mediated inactivation of Cyclin B (R-HSA-75035 )
Transcriptional Regulation by E2F6 (R-HSA-8953750 )
Signaling by SCF-KIT (R-HSA-1433557 )

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Familial ovarian cancer DISGLR2C No Known Autosomal dominant [1]
Hereditary breast carcinoma DISAEZT5 No Known Autosomal dominant [1]
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Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
This DOT Affected the Drug Response of 3 Drug(s)
Drug Name Drug ID Highest Status Interaction REF
Etoposide DMNH3PG Approved Serine/threonine-protein kinase Chk1 (CHEK1) affects the response to substance of Etoposide. [62]
Curcumin DMQPH29 Phase 3 Serine/threonine-protein kinase Chk1 (CHEK1) decreases the response to substance of Curcumin. [63]
Camptothecin DM6CHNJ Phase 3 Serine/threonine-protein kinase Chk1 (CHEK1) decreases the response to substance of Camptothecin. [40]
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52 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 Serine/threonine-protein kinase Chk1 (CHEK1). [2]
Ciclosporin DMAZJFX Approved Ciclosporin decreases the expression of Serine/threonine-protein kinase Chk1 (CHEK1). [3]
Tretinoin DM49DUI Approved Tretinoin decreases the expression of Serine/threonine-protein kinase Chk1 (CHEK1). [4]
Acetaminophen DMUIE76 Approved Acetaminophen increases the expression of Serine/threonine-protein kinase Chk1 (CHEK1). [5]
Doxorubicin DMVP5YE Approved Doxorubicin decreases the expression of Serine/threonine-protein kinase Chk1 (CHEK1). [6]
Cupric Sulfate DMP0NFQ Approved Cupric Sulfate decreases the expression of Serine/threonine-protein kinase Chk1 (CHEK1). [7]
Cisplatin DMRHGI9 Approved Cisplatin decreases the expression of Serine/threonine-protein kinase Chk1 (CHEK1). [8]
Estradiol DMUNTE3 Approved Estradiol increases the expression of Serine/threonine-protein kinase Chk1 (CHEK1). [9]
Quercetin DM3NC4M Approved Quercetin decreases the expression of Serine/threonine-protein kinase Chk1 (CHEK1). [10]
Temozolomide DMKECZD Approved Temozolomide increases the expression of Serine/threonine-protein kinase Chk1 (CHEK1). [11]
Hydrogen peroxide DM1NG5W Approved Hydrogen peroxide decreases the expression of Serine/threonine-protein kinase Chk1 (CHEK1). [13]
Carbamazepine DMZOLBI Approved Carbamazepine affects the expression of Serine/threonine-protein kinase Chk1 (CHEK1). [14]
Methotrexate DM2TEOL Approved Methotrexate increases the expression of Serine/threonine-protein kinase Chk1 (CHEK1). [15]
Menadione DMSJDTY Approved Menadione decreases the expression of Serine/threonine-protein kinase Chk1 (CHEK1). [13]
Fluorouracil DMUM7HZ Approved Fluorouracil increases the expression of Serine/threonine-protein kinase Chk1 (CHEK1). [17]
Folic acid DMEMBJC Approved Folic acid affects the expression of Serine/threonine-protein kinase Chk1 (CHEK1). [18]
Cannabidiol DM0659E Approved Cannabidiol decreases the expression of Serine/threonine-protein kinase Chk1 (CHEK1). [19]
Troglitazone DM3VFPD Approved Troglitazone decreases the expression of Serine/threonine-protein kinase Chk1 (CHEK1). [20]
Azathioprine DMMZSXQ Approved Azathioprine decreases the expression of Serine/threonine-protein kinase Chk1 (CHEK1). [21]
Diclofenac DMPIHLS Approved Diclofenac affects the expression of Serine/threonine-protein kinase Chk1 (CHEK1). [14]
Zidovudine DM4KI7O Approved Zidovudine decreases the expression of Serine/threonine-protein kinase Chk1 (CHEK1). [24]
Digitoxin DMWVIGP Approved Digitoxin decreases the expression of Serine/threonine-protein kinase Chk1 (CHEK1). [28]
AC220 DM8Y4JS Approved AC220 decreases the expression of Serine/threonine-protein kinase Chk1 (CHEK1). [29]
Furazolidone DM3P6V7 Approved Furazolidone increases the expression of Serine/threonine-protein kinase Chk1 (CHEK1). [31]
Berberine DMC5Q8X Phase 4 Berberine increases the expression of Serine/threonine-protein kinase Chk1 (CHEK1). [33]
SNDX-275 DMH7W9X Phase 3 SNDX-275 decreases the expression of Serine/threonine-protein kinase Chk1 (CHEK1). [29]
Resveratrol DM3RWXL Phase 3 Resveratrol decreases the expression of Serine/threonine-protein kinase Chk1 (CHEK1). [34]
Napabucasin DMDZ6Q3 Phase 3 Napabucasin decreases the expression of Serine/threonine-protein kinase Chk1 (CHEK1). [35]
Genistein DM0JETC Phase 2/3 Genistein increases the expression of Serine/threonine-protein kinase Chk1 (CHEK1). [9]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene decreases the expression of Serine/threonine-protein kinase Chk1 (CHEK1). [36]
(+)-JQ1 DM1CZSJ Phase 1 (+)-JQ1 decreases the expression of Serine/threonine-protein kinase Chk1 (CHEK1). [37]
Mivebresib DMCPF90 Phase 1 Mivebresib decreases the expression of Serine/threonine-protein kinase Chk1 (CHEK1). [39]
LMP400 DM4FW2E Phase 1 LMP400 increases the expression of Serine/threonine-protein kinase Chk1 (CHEK1). [40]
PMID28460551-Compound-2 DM4DOUB Patented PMID28460551-Compound-2 decreases the expression of Serine/threonine-protein kinase Chk1 (CHEK1). [41]
PMID26882240-Compound-32 DMJS4RP Patented PMID26882240-Compound-32 decreases the expression of Serine/threonine-protein kinase Chk1 (CHEK1). [43]
THAPSIGARGIN DMDMQIE Preclinical THAPSIGARGIN decreases the expression of Serine/threonine-protein kinase Chk1 (CHEK1). [44]
Dioscin DM5H2W9 Preclinical Dioscin decreases the expression of Serine/threonine-protein kinase Chk1 (CHEK1). [45]
Wortmannin DM8EVK5 Terminated Wortmannin decreases the expression of Serine/threonine-protein kinase Chk1 (CHEK1). [46]
Bisphenol A DM2ZLD7 Investigative Bisphenol A decreases the expression of Serine/threonine-protein kinase Chk1 (CHEK1). [47]
Trichostatin A DM9C8NX Investigative Trichostatin A decreases the expression of Serine/threonine-protein kinase Chk1 (CHEK1). [48]
Coumestrol DM40TBU Investigative Coumestrol increases the expression of Serine/threonine-protein kinase Chk1 (CHEK1). [50]
Deguelin DMXT7WG Investigative Deguelin increases the expression of Serine/threonine-protein kinase Chk1 (CHEK1). [51]
Glyphosate DM0AFY7 Investigative Glyphosate decreases the expression of Serine/threonine-protein kinase Chk1 (CHEK1). [53]
geraniol DMS3CBD Investigative geraniol decreases the expression of Serine/threonine-protein kinase Chk1 (CHEK1). [54]
[3H]methyltrienolone DMTSGOW Investigative [3H]methyltrienolone increases the expression of Serine/threonine-protein kinase Chk1 (CHEK1). [55]
acrolein DMAMCSR Investigative acrolein increases the expression of Serine/threonine-protein kinase Chk1 (CHEK1). [56]
3,7,3',4'-TETRAHYDROXYFLAVONE DMES906 Investigative 3,7,3',4'-TETRAHYDROXYFLAVONE increases the expression of Serine/threonine-protein kinase Chk1 (CHEK1). [57]
Choline DM5D9YK Investigative Choline affects the expression of Serine/threonine-protein kinase Chk1 (CHEK1). [58]
USNIC ACID DMGOURX Investigative USNIC ACID increases the expression of Serine/threonine-protein kinase Chk1 (CHEK1). [59]
RGFP966 DME9T0A Investigative RGFP966 decreases the expression of Serine/threonine-protein kinase Chk1 (CHEK1). [29]
G6976 DMEZO4M Investigative G6976 decreases the activity of Serine/threonine-protein kinase Chk1 (CHEK1). [61]
STAUROSPORINONE DMU2H4K Investigative STAUROSPORINONE decreases the activity of Serine/threonine-protein kinase Chk1 (CHEK1). [61]
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⏷ Show the Full List of 52 Drug(s)
17 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Arsenic trioxide DM61TA4 Approved Arsenic trioxide increases the phosphorylation of Serine/threonine-protein kinase Chk1 (CHEK1). [12]
Irinotecan DMP6SC2 Approved Irinotecan increases the phosphorylation of Serine/threonine-protein kinase Chk1 (CHEK1). [22]
Mitomycin DMH0ZJE Approved Mitomycin increases the phosphorylation of Serine/threonine-protein kinase Chk1 (CHEK1). [23]
Melphalan DMOLNHF Approved Melphalan increases the phosphorylation of Serine/threonine-protein kinase Chk1 (CHEK1). [23]
Liothyronine DM6IR3P Approved Liothyronine increases the phosphorylation of Serine/threonine-protein kinase Chk1 (CHEK1). [25]
Hydroxyurea DMOQVU9 Approved Hydroxyurea increases the phosphorylation of Serine/threonine-protein kinase Chk1 (CHEK1). [26]
Artesunate DMR27C8 Approved Artesunate increases the phosphorylation of Serine/threonine-protein kinase Chk1 (CHEK1). [27]
Olaparib DM8QB1D Approved Olaparib increases the phosphorylation of Serine/threonine-protein kinase Chk1 (CHEK1). [30]
SR141716A DMCO5JZ Approved SR141716A decreases the phosphorylation of Serine/threonine-protein kinase Chk1 (CHEK1). [32]
TAK-243 DM4GKV2 Phase 1 TAK-243 increases the sumoylation of Serine/threonine-protein kinase Chk1 (CHEK1). [38]
PMID28870136-Compound-52 DMFDERP Patented PMID28870136-Compound-52 decreases the phosphorylation of Serine/threonine-protein kinase Chk1 (CHEK1). [42]
Coumarin DM0N8ZM Investigative Coumarin decreases the phosphorylation of Serine/threonine-protein kinase Chk1 (CHEK1). [49]
3R14S-OCHRATOXIN A DM2KEW6 Investigative 3R14S-OCHRATOXIN A decreases the acetylation of Serine/threonine-protein kinase Chk1 (CHEK1). [52]
2-AMINO-1-METHYL-6-PHENYLIMIDAZO[4,5-B]PYRIDINE DMNQL17 Investigative 2-AMINO-1-METHYL-6-PHENYLIMIDAZO[4,5-B]PYRIDINE increases the phosphorylation of Serine/threonine-protein kinase Chk1 (CHEK1). [26]
N-nonylphenol DMH3OUX Investigative N-nonylphenol increases the phosphorylation of Serine/threonine-protein kinase Chk1 (CHEK1). [26]
Tetramethylbutylphenol DMW9CH2 Investigative Tetramethylbutylphenol increases the phosphorylation of Serine/threonine-protein kinase Chk1 (CHEK1). [26]
NORCANTHARIDIN DM9B6Y1 Investigative NORCANTHARIDIN increases the phosphorylation of Serine/threonine-protein kinase Chk1 (CHEK1). [60]
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⏷ Show the Full List of 17 Drug(s)
1 Drug(s) Affected the Protein Interaction/Cellular Processes of This DOT
Drug Name Drug ID Highest Status Interaction REF
Decitabine DMQL8XJ Approved Decitabine affects the localization of Serine/threonine-protein kinase Chk1 (CHEK1). [16]
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References

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