Id: acc4590
Group: 1sens
Protein: Chk1
Gene Symbol: CHEK1
Protein Id: O14757
Protein Name: CHK1_HUMAN
PTM: phosphorylation
Site: Ser345
Site Sequence: DKLVQGISFSQPTCPDHMLLN
Disease Category: Other
Disease: Excessive Mitotic Abnormalities
Disease Subtype:
Disease Cellline: AG11395
Disease Info:
Drug: camptothecin
Drug Info: "Camptothecin is a natural alkaloid with anti - tumor properties, which can inhibit the activity of topoisomerase I."
Effect: modulate
Effect Info: "After camptothecin treatment, the loss of WRN exonuclease stimulates fork inactivation and the accumulation of parental gaps, thereby engaging RAD51. This mechanism affects the enhancement of CHK1 phosphorylation and results in the persistence of RAD51 during the recovery from treatment. Notably, in WRN exonuclease - defective cells, the persistence of RAD51 is associated with elevated mitotic phosphorylation of MUS81 at Ser88, which is crucial for preventing excessive mitotic abnormalities."
Note:
Score: 4.0
Pubmed(PMID): 31114910
Sentence Index:
Sentence:

Sequence & Structure:

MAVPFVEDWDLVQTLGEGAYGEVQLAVNRVTEEAVAVKIVDMKRAVDCPENIKKEICINKMLNHENVVKFYGHRREGNIQYLFLEYCSGGELFDRIEPDIGMPEPDAQRFFHQLMAGVVYLHGIGITHRDIKPENLLLDERDNLKISDFGLATVFRYNNRERLLNKMCGTLPYVAPELLKRREFHAEPVDVWSCGIVLTAMLAGELPWDQPSDSCQEYSDWKEKKTYLNPWKKIDSAPLALLHKILVENPSARITIPDIKKDRWYNKPLKKGAKRPRVTSGGVSESPSGFSKHIQSNLDFSPVNSASSEENVKYSSSQPEPRTGLSLWDTSPSYIDKLVQGISFSQPTCPDHMLLNSQLLGTPGSSQNPWQRLVKRMTRFFTKLDADKSYQCLKETCEKLGYQWKKSCMNQVTISTTDRRNNKLIFKVNLLEMDDKILVDFRLSKGDGLEFKRHFLKIKGKLIDIVSSQKIWLPAT

Select PDB:

Known Drugs:

source: Multi-Sources

(see table)

Target Drug name MOA Phase Status Disease Source
CHEK1 UCN-01 Serine/threonine-protein kinase Chk1 inhibitor 2 Terminated lymphoma ClinicalTrials
CHEK1 PREXASERTIB Serine/threonine-protein kinase Chk1 inhibitor 2 Completed small cell lung carcinoma ClinicalTrials
CHEK1 UCN-01 Serine/threonine-protein kinase Chk1 inhibitor 2 Completed small cell lung carcinoma ClinicalTrials
CHEK1 UCN-01 Serine/threonine-protein kinase Chk1 inhibitor 2 Terminated melanoma ClinicalTrials
CHEK1 UCN-01 Serine/threonine-protein kinase Chk1 inhibitor 2 Completed pancreatic carcinoma ClinicalTrials
CHEK1 RABUSERTIB Serine/threonine-protein kinase Chk1 inhibitor 2 Completed non-small cell lung carcinoma ClinicalTrials
CHEK1 UCN-01 Serine/threonine-protein kinase Chk1 inhibitor 2 Completed peritoneum cancer ClinicalTrials
CHEK1 UCN-01 Serine/threonine-protein kinase Chk1 inhibitor 2 Completed fallopian tube cancer ClinicalTrials
CHEK1 UCN-01 Serine/threonine-protein kinase Chk1 inhibitor 2 Unknown status kidney cancer ClinicalTrials
CHEK1 PREXASERTIB Serine/threonine-protein kinase Chk1 inhibitor 2 Completed cancer ClinicalTrials
CHEK1 PREXASERTIB Serine/threonine-protein kinase Chk1 inhibitor 2 Completed ovarian cancer ClinicalTrials
CHEK1 PREXASERTIB Serine/threonine-protein kinase Chk1 inhibitor 2 Terminated ovarian cancer ClinicalTrials
CHEK1 PREXASERTIB Serine/threonine-protein kinase Chk1 inhibitor 2 Terminated breast cancer ClinicalTrials
CHEK1 UCN-01 Serine/threonine-protein kinase Chk1 inhibitor 2 Completed ovarian cancer ClinicalTrials
CHEK1 XL-844 Serine/threonine-protein kinase Chk1 inhibitor 1 Terminated chronic lymphocytic leukemia ClinicalTrials
CHEK1 SCH-900776 Serine/threonine-protein kinase Chk1 inhibitor 1 Completed Hodgkins lymphoma ClinicalTrials
CHEK1 PREXASERTIB Serine/threonine-protein kinase Chk1 inhibitor 1 Completed acute myeloid leukemia ClinicalTrials
CHEK1 UCN-01 Serine/threonine-protein kinase Chk1 inhibitor 1 Completed acute erythroleukemia ClinicalTrials
CHEK1 PREXASERTIB Serine/threonine-protein kinase Chk1 inhibitor 1 Completed myelodysplastic syndrome ClinicalTrials
CHEK1 UCN-01 Serine/threonine-protein kinase Chk1 inhibitor 1 Completed myelodysplastic syndrome ClinicalTrials
ClinicalTrials
CHEK1 UCN-01 Serine/threonine-protein kinase Chk1 inhibitor 1 Completed acute monocytic leukemia ClinicalTrials
CHEK1 UCN-01 Serine/threonine-protein kinase Chk1 inhibitor 1 Completed acute myelomonocytic leukemia ClinicalTrials
CHEK1 SCH-900776 Serine/threonine-protein kinase Chk1 inhibitor 1 Terminated acute lymphoblastic leukemia ClinicalTrials
CHEK1 SCH-900776 Serine/threonine-protein kinase Chk1 inhibitor 1 Terminated acute myeloid leukemia ClinicalTrials
CHEK1 UCN-01 Serine/threonine-protein kinase Chk1 inhibitor 1 Completed acute promyelocytic leukemia ClinicalTrials

Note: Only show clinically investigational or approved drugs with protein targets.

Protein Tractability:

source: Open Targets
Small molecule
Antibody
PROTAC
Other modalities
Approved Drug
Advanced Clinical
Phase 1 Clinical
Structure with Ligand
High-Quality Ligand
High-Quality Pocket
Med-Quality Pocket
Druggable Family
Approved Drug
Advanced Clinical
Phase 1 Clinical
UniProt loc high conf
GO CC high conf
UniProt loc med conf
UniProt SigP or TMHMM
GO CC med conf
Human Protein Atlas loc
Approved Drug
Advanced Clinical
Phase 1 Clinical
Literature
UniProt Ubiquitination
Database Ubiquitination
Half-life Data
Small Molecule Binder
Approved Drug
Advanced Clinical
Phase 1 Clinical

PTM Intensity:

source: CPTAC

No intensity data of this site,
show all other sites!

CHEK1-Ser286
Cancer Intensity
BRCA -0.573
COAD
HGSC -0.61
ccRCC
GBM
HNSC -0.303
LUAD
LUSC
non_ccRCC
PDAC
UCEC 1.486
CHEK1-Ser296
Cancer Intensity
BRCA
COAD 0.707
HGSC -0.707
ccRCC
GBM
HNSC
LUAD
LUSC
non_ccRCC
PDAC
UCEC
CHEK1-Ser301
Cancer Intensity
BRCA
COAD 0.707
HGSC -0.707
ccRCC
GBM
HNSC
LUAD
LUSC
non_ccRCC
PDAC
UCEC
CHEK1-Ser317
Cancer Intensity
BRCA
COAD 0.707
HGSC -0.707
ccRCC
GBM
HNSC
LUAD
LUSC
non_ccRCC
PDAC
UCEC
CHEK1-Ser331
Cancer Intensity
BRCA
COAD 0.941
HGSC -1.05
ccRCC
GBM
HNSC 0.11
LUAD
LUSC
non_ccRCC
PDAC
UCEC

PTM-Disease Association:

source: PTMD
Residue Position State Disease Class PMID
S 345 D Riddle syndrome Phosphorylation 17940005
S 345 U Colorectal cancer Phosphorylation 32357935
S 345 U Head and neck squamous cell carcinoma Phosphorylation 21281788
S 345 U Multiple myeloma Phosphorylation 35190641

State Note: Based on the distinct PTM states in diseases, PTMD classified all disease-associated PTMs into six classes, including whether the up-regulation (U) or down-regulation (D) of PTM levels, the absence (A) or presence (P) of PTMs, and the creation (C) or disruption (N) of PTM sites are associated with diseases.

PTM-Drug Perturbation Response:

source: DecryptM

No data.

Function score:

source: funscoR

No data.

Cross Links: