Id: acc1323
Group: 2sens
Protein: Chk1
Gene Symbol: CHEK1
Protein Id: O14757
Protein Name: CHK1_HUMAN
PTM: phosphorylation
Site: Ser317
Site Sequence: SEENVKYSSSQPEPRTGLSLW
Disease Category: Cancer
Disease: Melanoma
Disease Subtype: PLX4032-res
Disease Cellline: WM9(PLX4032-res)
Disease Info:
Drug: PLX4032 + PF477736
Drug Info: PLX4032 (Vemurafenib) is a BRAF kinase inhibitor used for the treatment of patients with unresectable or metastatic melanoma harboring BRAF V600E mutations. PF477736: -
Effect: modulate
Effect Info: "Combined treatment with PLX4032 and PF477736 reduced the levels of total Chk1 protein and Chk1 phosphorylation at the S280 and S296 sites, but increased the phosphorylation levels of Chk1 at the S317 and S345 sites in both PLX4032-sensitive and -resistant melanoma cells. Moreover, PF477736 triggered the re - acquisition of sensitivity to PLX4032 in PLX4032-resistant melanoma cells."
Note: drug comb
Score: 4.0
Pubmed(PMID): 30100999
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
CHEK1-Ser317
Cancer Intensity
BRCA
COAD 0.707
HGSC -0.707
ccRCC
GBM
HNSC
LUAD
LUSC
non_ccRCC
PDAC
UCEC

PTM-Disease Association:

source: PTMD
Residue Position State Disease Class PMID
S 317 U Colorectal cancer Phosphorylation 32357935
S 317 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: