PMADS

Id:	acc2121
Group:	2sens
Protein:	Cdc2
Gene Symbol:	CDK1
Protein Id:	P06493
Protein Name:	CDK1_HUMAN
PTM:	phosphorylation
Site:	Tyr15
Site Sequence:	KIEKIGEGTYGVVYKGRHKTT
Disease Category:	Cancer
Disease:	Breast Cancer
Disease Subtype:
Disease Cellline:	SK-BR-3
Disease Info:
Drug:	Taxol
Drug Info:	"Taxol (paclitaxel) is a chemotherapeutic agent that stabilizes microtubules to inhibit cancer cell division, primarily used in the treatment of ovarian, breast, and lung cancers."
Effect:	inhibit
Effect Info:	"Herceptin reduces the inhibitory phosphorylation of Cdc2 at the Tyr - 15 site, and cells show enhanced responses to paclitaxel - induced apoptosis and cytotoxicity."
Note:
Score:	5.0
Pubmed(PMID):	12384528
Sentence Index:	12384528_3-4
Sentence:	"Because activation of p34(Cdc2) is required for Taxol-induced apoptosis and because overexpression of ErbB2 blocks Taxol-induced apoptosis by inhibiting p34(Cdc2) activation, we studied the effect of Herceptin treatment on p34(Cdc2) kinase activation and apoptosis in Taxol-treated human breast carcinoma cell lines MDA-MB-435, SKBr3, MDA-MB-453, and 435.eB, which is an ErbB2 transfectant of MDA-MB-435. Herceptin treatment down-regulated ErbB2, reduced the inhibitory phosphorylation of Cdc2 on Tyr-15, and down-regulated the expression of p21(Cip1), a Cdc2 inhibitor."

Sequence & Structure:

MEDYTKIEKIGEGTYGVVYKGRHKTTGQVVAMKKIRLESEEEGVPSTAIREISLLKELRHPNIVSLQDVLMQDSRLYLIFEFLSMDLKKYLDSIPPGQYMDSSLVKSYLYQILQGIVFCHSRRVLHRDLKPQNLLIDDKGTIKLADFGLARAFGIPIRVYTHEVVTLWYRSPEVLLGSARYSTPVDIWSIGTIFAELATKKPLFHGDSEIDQLFRIFRALGTPNNEVWPEVESLQDYKNTFPKWKPGSLASHVKNLDENGLDLLSKMLIYDPAKRISGKMALNHPYFNDLDNQIKKM

Select PDB:

Known Drugs:

source: Multi-Sources

(see table)

Target	Drug name	MOA	Phase	Status	Disease	Source
CDK1	DINACICLIB	Cyclin-dependent kinase 1 inhibitor	3	Completed	chronic lymphocytic leukemia	ClinicalTrials
CDK1	ALVOCIDIB	Cyclin-dependent kinase 1 inhibitor	2	Completed	chronic lymphocytic leukemia	ClinicalTrials ClinicalTrials
CDK1	AT-7519	Cyclin-dependent kinase inhibitor	2	Completed	chronic lymphocytic leukemia	ClinicalTrials
CDK1	MILCICLIB	Cyclin-dependent kinase 1 inhibitor	2	Completed	hepatocellular carcinoma	ClinicalTrials
CDK1	ALVOCIDIB	Cyclin-dependent kinase 1 inhibitor	2	Terminated	chronic lymphocytic leukemia	ClinicalTrials
CDK1	ALVOCIDIB	Cyclin-dependent kinase 1 inhibitor	2	Terminated	acute myeloid leukemia	ClinicalTrials ClinicalTrials
CDK1	DINACICLIB	Cyclin-dependent kinase 1 inhibitor	2	Terminated	acute lymphoblastic leukemia	ClinicalTrials
CDK1	DINACICLIB	Cyclin-dependent kinase 1 inhibitor	2	Terminated	acute myeloid leukemia	ClinicalTrials
CDK1	ALVOCIDIB	Cyclin-dependent kinase 1 inhibitor	2	Completed	cutaneous melanoma	ClinicalTrials
CDK1	ALVOCIDIB	Cyclin-dependent kinase 1 inhibitor	2	Completed	lymphoma	ClinicalTrials ClinicalTrials
CDK1	RONICICLIB	Cyclin-dependent kinase inhibitor	2	Withdrawn	neoplasm	ClinicalTrials
CDK1	ALVOCIDIB	Cyclin-dependent kinase 1 inhibitor	2	Completed	sarcoma	ClinicalTrials
CDK1	RONICICLIB	Cyclin-dependent kinase inhibitor	2	Terminated	small cell lung carcinoma	ClinicalTrials
CDK1	ALVOCIDIB	Cyclin-dependent kinase 1 inhibitor	2	Completed	multiple myeloma	ClinicalTrials
CDK1	DINACICLIB	Cyclin-dependent kinase 1 inhibitor	2	Completed	multiple myeloma	ClinicalTrials
CDK1	SELICICLIB	Cyclin-dependent kinase 1 inhibitor	2	Terminated	non-small cell lung carcinoma	ClinicalTrials
CDK1	ALVOCIDIB	Cyclin-dependent kinase 1 inhibitor	2	Completed	pancreatic carcinoma	ClinicalTrials
CDK1	ALVOCIDIB	Cyclin-dependent kinase 1 inhibitor	2	Completed	pancreatic adenocarcinoma	ClinicalTrials
CDK1	MILCICLIB	Cyclin-dependent kinase 1 inhibitor	2	Terminated	Thymic Carcinoma	ClinicalTrials
CDK1	MILCICLIB	Cyclin-dependent kinase 1 inhibitor	2	Terminated	Thymoma	ClinicalTrials
CDK1	SELICICLIB	Cyclin-dependent kinase 1 inhibitor	2	Recruiting	pituitary-dependent Cushing's disease	ClinicalTrials
CDK1	SELICICLIB	Cyclin-dependent kinase 1 inhibitor	2	Terminated	pituitary-dependent Cushing's disease	ClinicalTrials
CDK1	AT-7519	Cyclin-dependent kinase inhibitor	2	Completed	Mantle cell lymphoma	ClinicalTrials
CDK1	ALVOCIDIB	Cyclin-dependent kinase 1 inhibitor	2	Terminated	prolymphocytic leukemia	ClinicalTrials
CDK1	DINACICLIB	Cyclin-dependent kinase 1 inhibitor	2	Active, not recruiting	mucosal melanoma	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

CDK1-Tyr15
Cancer	Intensity
BRCA	-0.179
COAD	-0.261
HGSC	-0.161
ccRCC	0.837
GBM
HNSC	0.911
LUAD	-0.288
LUSC	-1.994
non_ccRCC
PDAC
UCEC	1.134

PTM-Disease Association:

source: PTMD

Residue	Position	State	Disease	Class	PMID
Y	15	U	Cancer	Phosphorylation	24391984
Y	15	U	Vulvar cancer	Phosphorylation	25849598

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:

CTD
DMRdb