PMADS

Id:	acc1790
Group:	2sens
Protein:	GSK3beta
Gene Symbol:	GSK3B
Protein Id:	P49841
Protein Name:	GSK3B_HUMAN
PTM:	phosphorylation
Site:	Ser9
Site Sequence:	-MSGRPRTTSFAESCKPVQQP
Disease Category:	Cancer
Disease:	Colorectal Cancer
Disease Subtype:
Disease Cellline:	HCT116
Disease Info:
Drug:	Enzastaurin
Drug Info:	"Enzastaurin is a potent and selective protein kinase C beta (PKCbeta) inhibitor with an IC50 value of 6 nM, demonstrating 6-20 times higher selectivity for PKCbeta compared to other PKC isoforms such as PKCalpha, PKCgamma, and PKCepsilon."
Effect:	modulate
Effect Info:	"Enzastaurin treatment can inhibit the phosphorylation of GSK3beta in tumor tissues and PBMCs, which indicates that GSK3beta phosphorylation can serve as a reliable pharmacodynamic marker for Enzastaurin activity."
Note:
Score:	4.0
Pubmed(PMID):	16103100
Sentence Index:	16103100_10-11
Sentence:	"These data show that Enzastaurin has a direct antitumor effect and that Enzastaurin treatment suppresses GSK3beta phosphorylation in both tumor tissue and in PBMCs, suggesting that GSK3beta phosphorylation may serve as a reliable pharmacodynamic marker for Enzastaurin activity. With previously published reports, these data support the notion that Enzastaurin suppresses tumor growth through multiple mechanisms: direct suppression of tumor cell proliferation and the induction of tumor cell death coupled to the indirect effect of suppressing tumor-induced angiogenesis."

Sequence & Structure:

MSGRPRTTSFAESCKPVQQPSAFGSMKVSRDKDGSKVTTVVATPGQGPDRPQEVSYTDTKVIGNGSFGVVYQAKLCDSGELVAIKKVLQDKRFKNRELQIMRKLDHCNIVRLRYFFYSSGEKKDEVYLNLVLDYVPETVYRVARHYSRAKQTLPVIYVKLYMYQLFRSLAYIHSFGICHRDIKPQNLLLDPDTAVLKLCDFGSAKQLVRGEPNVSYICSRYYRAPELIFGATDYTSSIDVWSAGCVLAELLLGQPIFPGDSGVDQLVEIIKVLGTPTREQIREMNPNYTEFKFPQIKAHPWTKVFRPRTPPEAIALCSRLLEYTPTARLTPLEACAHSFFDELRDPNVKLPNGRDTPALFNFTTQELSSNPPLATILIPPHARIQAAASTPTNATAASDANTGDRGQTNNAASASASNST

Select PDB:

Known Drugs:

source: Multi-Sources

(see table)

Target	Drug name	MOA	Phase	Status	Disease	Source
GSK3B	LITHIUM CARBONATE	Glycogen synthase kinase-3 inhibitor	4	-	bipolar I disorder	DailyMed DailyMed DailyMed
GSK3B	LITHIUM CARBONATE	Glycogen synthase kinase-3 inhibitor	4	Completed	bipolar I disorder	ClinicalTrials ClinicalTrials
GSK3B	LITHIUM CARBONATE	Glycogen synthase kinase-3 inhibitor	4	Withdrawn	bipolar I disorder	ClinicalTrials
GSK3B	LITHIUM CARBONATE	Glycogen synthase kinase-3 inhibitor	4	Unknown status	bipolar I disorder	ClinicalTrials ClinicalTrials
GSK3B	LITHIUM CITRATE	Glycogen synthase kinase-3 inhibitor	4	-	bipolar I disorder	DailyMed
GSK3B	LITHIUM CARBONATE	Glycogen synthase kinase-3 inhibitor	4	Completed	depressive disorder	ClinicalTrials ClinicalTrials ClinicalTrials ClinicalTrials ClinicalTrials ClinicalTrials ClinicalTrials
GSK3B	LITHIUM CARBONATE	Glycogen synthase kinase-3 inhibitor	4	Terminated	depressive disorder	ClinicalTrials
GSK3B	LITHIUM CARBONATE	Glycogen synthase kinase-3 inhibitor	4	Unknown status	depressive disorder	ClinicalTrials ClinicalTrials ClinicalTrials
GSK3B	LITHIUM CARBONATE	Glycogen synthase kinase-3 inhibitor	4	-	major depressive disorder	DailyMed
GSK3B	LITHIUM CARBONATE	Glycogen synthase kinase-3 inhibitor	4	Recruiting	depressive disorder	ClinicalTrials
GSK3B	LITHIUM CARBONATE	Glycogen synthase kinase-3 inhibitor	4	Completed	bipolar disorder	ClinicalTrials ClinicalTrials ClinicalTrials ClinicalTrials ClinicalTrials ClinicalTrials ClinicalTrials ClinicalTrials ClinicalTrials ClinicalTrials ClinicalTrials ClinicalTrials ClinicalTrials ClinicalTrials ClinicalTrials ClinicalTrials ClinicalTrials ClinicalTrials ClinicalTrials ClinicalTrials ClinicalTrials ClinicalTrials ClinicalTrials
GSK3B	LITHIUM CARBONATE	Glycogen synthase kinase-3 inhibitor	4	Unknown status	bipolar disorder	ClinicalTrials ClinicalTrials ClinicalTrials ClinicalTrials
GSK3B	LITHIUM CARBONATE	Glycogen synthase kinase-3 inhibitor	4	-	bipolar disorder	DailyMed DailyMed DailyMed DailyMed DailyMed DailyMed DailyMed DailyMed DailyMed DailyMed DailyMed DailyMed DailyMed DailyMed DailyMed DailyMed DailyMed DailyMed DailyMed DailyMed DailyMed DailyMed DailyMed DailyMed DailyMed DailyMed DailyMed DailyMed DailyMed DailyMed DailyMed DailyMed DailyMed DailyMed DailyMed DailyMed DailyMed DailyMed DailyMed DailyMed DailyMed DailyMed DailyMed DailyMed DailyMed
GSK3B	LITHIUM CARBONATE	Glycogen synthase kinase-3 inhibitor	4	Recruiting	bipolar disorder	ClinicalTrials ClinicalTrials
GSK3B	LITHIUM CARBONATE	Glycogen synthase kinase-3 inhibitor	4	Terminated	bipolar disorder	ClinicalTrials ClinicalTrials ClinicalTrials ClinicalTrials
GSK3B	LITHIUM CARBONATE	Glycogen synthase kinase-3 inhibitor	4	Withdrawn	bipolar disorder	ClinicalTrials ClinicalTrials
GSK3B	LITHIUM CARBONATE	Glycogen synthase kinase-3 inhibitor	3	Completed	stroke	ClinicalTrials
GSK3B	LITHIUM CARBONATE	Glycogen synthase kinase-3 inhibitor	3	Recruiting	internal carotid artery stenosis	ClinicalTrials
GSK3B	LITHIUM CARBONATE	Glycogen synthase kinase-3 inhibitor	3	Completed	aggressive behavior	ClinicalTrials
GSK3B	LITHIUM CARBONATE	Glycogen synthase kinase-3 inhibitor	3	Recruiting	carotid artery disease	ClinicalTrials
GSK3B	LITHIUM CARBONATE	Glycogen synthase kinase-3 inhibitor	3	Active, not recruiting	autism spectrum disorder	ClinicalTrials
GSK3B	LITHIUM CARBONATE	Glycogen synthase kinase-3 inhibitor	3	Completed	conduct disorder	ClinicalTrials
GSK3B	LITHIUM CARBONATE	Glycogen synthase kinase-3 inhibitor	3	Terminated	anxiety	ClinicalTrials
GSK3B	LITHIUM CARBONATE	Glycogen synthase kinase-3 inhibitor	3	Completed	treatment resistant depression	ClinicalTrials
GSK3B	LITHIUM CARBONATE	Glycogen synthase kinase-3 inhibitor	3	Completed	bipolar I disorder	ClinicalTrials ClinicalTrials ClinicalTrials 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

GSK3B-Ser9
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	9	D	Diabetes mellitus	Phosphorylation	15033922
S	9	D	Pancreatic cancer/carcinoma/adenocarcinoma	Phosphorylation	23408967
S	9	D	Triple-negative breast cancer	Phosphorylation	35090098
S	9	D	Alzheimer's disease	Phosphorylation	22278060
S	9	D	Schizophrenia	Phosphorylation	14745448
S	9	D	Parkinson's disease	Phosphorylation	27609071
S	9	P	Breast cancer	Phosphorylation	36632451
S	9	P	Ovarian cancer/carcinoma	Phosphorylation	23667667
S	9	P	Lung cancer/carcinoma	Phosphorylation	23149922
S	9	P	Liver cancer	Phosphorylation	23325562
S	9	P	Gastric cancer	Phosphorylation	23123500
S	9	U	Lung adenocarcinoma	Phosphorylation	33808696
S	9	U	Hepatocellular carcinoma	Phosphorylation	34484860
S	9	U	Breast cancer	Phosphorylation	17495324 ; 35173161 ; 17495324
S	9	U	Non-small cell lung cancer	Phosphorylation	36869126
S	9	U	Lung cancer/carcinoma	Phosphorylation	23514933
S	9	U	Melanoma	Phosphorylation	35347072
S	9	U	Systemic scleroderma	Phosphorylation	35853487
S	9	U	Systemic lupus erythematosus	Phosphorylation	23735868
S	9	U	Squamous cell carcinoma	Phosphorylation	18606491
S	9	U	Skin cancer	Phosphorylation	18606491
S	9	U	Papillomas	Phosphorylation	18606491
S	9	U	Ovarian cancer	Phosphorylation	15208673
S	9	U	Neuroblastoma	Phosphorylation	30154149
S	9	U	Major depressive disorder	Phosphorylation	22622071
S	9	U	Lymphoma	Phosphorylation	20224723
S	9	U	Granulomatosis with polyangiitis	Phosphorylation	37720230
S	9	U	Dilated cardiomyopathy	Phosphorylation	37852321
S	9	U	Diabetes mellitus	Phosphorylation	35835217
S	9	U	Cardiomyopathy	Phosphorylation	37852321
S	9	U	Breast cancer/tumor/carcinoma	Phosphorylation	17495324 ; 27494834
S	9	U	Bipolar disorder	Phosphorylation	16806104
S	9	U	Alzheimer's disease	Phosphorylation	22278060

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

Protein	Gene	PTM	Position	Modified sequence	Cell	Drug	pEC50	Regulation
P49841	GSK3B	P	Ser9	TTS(ph)FAESCKPVQQPSAFGSMK	HeLa	CUDC101	1	up
P49841	GSK3B	P	Ser9	TTS(ph)FAESCKPVQQPSAFGSMK	A459	MK2206	7.2049	down
P49841	GSK3B	P	Ser9	TTS(ph)FAESCKPVQQPSAFGSMK	A459	SelumetinibMK2206-1to2	7.4614	down
P49841	GSK3B	P	Ser9	TTS(ph)FAESCKPVQQPSAFGSMK	A459	SelumetinibMK2206-3to1	7.0611	down
P49841	GSK3B	P	Ser9	TTS(ph)FAESCKPVQQPSAFGSMK	PC-9	GeftinibAZD4547-1to80	8.6743	down
P49841	GSK3B	P	Ser9	TTS(ph)FAESCKPVQQPSAFGSMK	PC-9	Lapatinib	6.6407	down
P49841	GSK3B	P	Ser9	TTS(ph)FAESCKPVQQPSAFGSMK	A459	MK2206	7.0039	-
P49841	GSK3B	P	Ser9	TTS(ph)FAESCKPVQQPSAFGSMK	A459	Selumetinib	6.2144	-
P49841	GSK3B	P	Ser9	TTS(ph)FAESCKPVQQPSAFGSMK	HeLa	Curcumin	5.2589	-
P49841	GSK3B	P	Ser9	TTS(ph)FAESCKPVQQPSAFGSMK	PC-9	AZD4547	5.5148	-
P49841	GSK3B	P	Ser9	TTS(ph)FAESCKPVQQPSAFGSMK	PC-9	Gefitinib	8.2709	-

pEC50 Note: pEC50 is the negative logarithm of EC50 (half-maximal effective concentration, dosage unit Mol), calculated as pEC50 = -log10(EC50), which quantifies the potency of a drug or compound.

Function score:

source: funscoR

No data.

Cross Links:

CTD
DMRdb