| Id: | acc1185 |
| Group: | 2sens |
| Protein: | CHK1 |
| Gene Symbol: | CHEK1 |
| Protein Id: | O14757 |
| Protein Name: | CHK1_HUMAN |
| PTM: | phosphorylation |
| Site: | Ser345 |
| Site Sequence: | DKLVQGISFSQPTCPDHMLLN |
| Disease Category: | Cancer |
| Disease: | Breast Cancer |
| Disease Subtype: | |
| Disease Cellline: | MCF7 |
| Disease Info: | |
| Drug: | hydroxyurea |
| Drug Info: | "Hydroxyurea is a ribonucleotide reductase inhibitor that interferes with DNA synthesis by preventing the conversion of ribonucleotides to deoxyribonucleotides, primarily used in the treatment of chronic myelogenous leukemia, sickle cell disease, and certain solid tumors like melanoma and head/neck carcinomas. " |
| Effect: | inhibit |
| Effect Info: | Phosphorylation of CHK1 at the ser345 site is a specific marker of ATR activity. NU6027 sensitizes cells to DNA damage therapy by inhibiting ATR. |
| Note: | |
| Score: | 5.0 |
| Pubmed(PMID): | 21730979 |
| Sentence Index: | 21730979_3-4 |
| Sentence: | "As NU6027, originally developed as a CDK2 inhibitor, potentiated cisplatin in a CDK2-independent manner we postulated that it may inhibit ATR. METHODS: Cellular ATR kinase activity was determined by CHK1 phosphorylation in human fibroblasts with inducible dominant-negative ATR-kinase dead expression and human breast cancer MCF7 cells." |
Sequence & Structure:
MAVPFVEDWDLVQTLGEGAYGEVQLAVNRVTEEAVAVKIVDMKRAVDCPENIKKEICINKMLNHENVVKFYGHRREGNIQYLFLEYCSGGELFDRIEPDIGMPEPDAQRFFHQLMAGVVYLHGIGITHRDIKPENLLLDERDNLKISDFGLATVFRYNNRERLLNKMCGTLPYVAPELLKRREFHAEPVDVWSCGIVLTAMLAGELPWDQPSDSCQEYSDWKEKKTYLNPWKKIDSAPLALLHKILVENPSARITIPDIKKDRWYNKPLKKGAKRPRVTSGGVSESPSGFSKHIQSNLDFSPVNSASSEENVKYSSSQPEPRTGLSLWDTSPSYIDKLVQGISFSQPTCPDHMLLNSQLLGTPGSSQNPWQRLVKRMTRFFTKLDADKSYQCLKETCEKLGYQWKKSCMNQVTISTTDRRNNKLIFKVNLLEMDDKILVDFRLSKGDGLEFKRHFLKIKGKLIDIVSSQKIWLPAT
Select PDB:
| 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 TargetsPTM Intensity:
source: CPTACNo 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: DecryptMNo data.
Function score:
source: funscoRNo data.
