PMADS

Id:	acc1398
Group:	2sens
Protein:	AKT
Gene Symbol:	AKT1
Protein Id:	P31749
Protein Name:	AKT1_HUMAN
PTM:	phosphorylation
Site:	Ser473
Site Sequence:	ERRPHFPQFSYSASGTA----
Disease Category:	Cancer
Disease:	Leukemia
Disease Subtype:	AML
Disease Cellline:	KG-1
Disease Info:
Drug:	KP372-1
Drug Info:	"KP372-1 is a dual-function Akt inhibitor and NQO1 redox cycler that suppresses cancer cell proliferation, induces apoptosis and anoikis, and triggers DNA damage through reactive oxygen species (ROS) generation, demonstrating antitumor activity in head and neck squamous cell carcinoma and pancreatic cancer research. "
Effect:	modulate
Effect Info:	"KP372-1 directly inhibits the kinase activities of AKT, PDK1, and FLT3 in a concentration-dependent manner, significantly reducing the viability of AML cells."
Note:
Score:	4.0
Pubmed(PMID):	16585200
Sentence Index:	16585200_5-6
Sentence:	"Western blot analysis indicated that KP372-1 decreased the phosphorylation of AKT on both Ser(473) and Thr(308); abrogated the phosphorylation of p70S6 kinase, BAD, and Foxo3a via PI3K/AKT signaling; and down-regulated expression of PIM-1 through direct inhibition of FLT3. Treatment of AML cell lines with KP372-1 resulted in rapid generation of reactive oxygen species and stimulation of oxygen consumption, followed by mitochondrial depolarization, caspase activation, and phosphatidylserine externalization."

Sequence & Structure:

MSDVAIVKEGWLHKRGEYIKTWRPRYFLLKNDGTFIGYKERPQDVDQREAPLNNFSVAQCQLMKTERPRPNTFIIRCLQWTTVIERTFHVETPEEREEWTTAIQTVADGLKKQEEEEMDFRSGSPSDNSGAEEMEVSLAKPKHRVTMNEFEYLKLLGKGTFGKVILVKEKATGRYYAMKILKKEVIVAKDEVAHTLTENRVLQNSRHPFLTALKYSFQTHDRLCFVMEYANGGELFFHLSRERVFSEDRARFYGAEIVSALDYLHSEKNVVYRDLKLENLMLDKDGHIKITDFGLCKEGIKDGATMKTFCGTPEYLAPEVLEDNDYGRAVDWWGLGVVMYEMMCGRLPFYNQDHEKLFELILMEEIRFPRTLGPEAKSLLSGLLKKDPKQRLGGGSEDAKEIMQHRFFAGIVWQHVYEKKLSPPFKPQVTSETDTRYFDEEFTAQMITITPPDQDDSMECVDSERRPHFPQFSYSASGTA

Select PDB:

Known Drugs:

source: Multi-Sources

(see table)

Target	Drug name	MOA	Phase	Status	Disease	Source
AKT1	IPATASERTIB	Serine/threonine-protein kinase AKT inhibitor	3	Completed	metastatic prostate cancer	ClinicalTrials
AKT1	CAPIVASERTIB	Serine/threonine-protein kinase AKT inhibitor	3	Active, not recruiting	breast neoplasm	ClinicalTrials
AKT1	IPATASERTIB	Serine/threonine-protein kinase AKT inhibitor	3	Completed	triple-negative breast cancer	ClinicalTrials
AKT1	IPATASERTIB	Serine/threonine-protein kinase AKT inhibitor	3	Recruiting	cancer	ClinicalTrials
AKT1	IPATASERTIB	Serine/threonine-protein kinase AKT inhibitor	3	Active, not recruiting	breast cancer	ClinicalTrials
AKT1	IPATASERTIB	Serine/threonine-protein kinase AKT inhibitor	3	Completed	breast cancer	ClinicalTrials
AKT1	IPATASERTIB	Serine/threonine-protein kinase AKT inhibitor	3	Terminated	breast cancer	ClinicalTrials
AKT1	AFURESERTIB	Serine/threonine-protein kinase AKT inhibitor	3	Recruiting	breast cancer	ClinicalTrials
AKT1	CAPIVASERTIB	Serine/threonine-protein kinase AKT inhibitor	3	Active, not recruiting	breast cancer	ClinicalTrials
AKT1	CAPIVASERTIB	Serine/threonine-protein kinase AKT inhibitor	3	Recruiting	breast cancer	ClinicalTrials
AKT1	CAPIVASERTIB	Serine/threonine-protein kinase AKT inhibitor	3	Recruiting	prostate cancer	ClinicalTrials
AKT1	CAPIVASERTIB	Serine/threonine-protein kinase AKT inhibitor	3	Active, not recruiting	prostate cancer	ClinicalTrials
AKT1	MK-2206	Serine/threonine-protein kinase AKT inhibitor	2	Completed	hepatocellular carcinoma	ClinicalTrials
AKT1	MK-2206	Serine/threonine-protein kinase AKT inhibitor	2	Completed	head and neck squamous cell carcinoma	ClinicalTrials
AKT1	CAPIVASERTIB	Serine/threonine-protein kinase AKT inhibitor	2	Active, not recruiting	neoplasm of mature B-cells	ClinicalTrials
AKT1	UPROSERTIB	Serine/threonine-protein kinase AKT inhibitor	2	Terminated	acute myeloid leukemia	ClinicalTrials
AKT1	CAPIVASERTIB	Serine/threonine-protein kinase AKT inhibitor	2	Active, not recruiting	adenocarcinoma	ClinicalTrials
AKT1	MK-2206	Serine/threonine-protein kinase AKT inhibitor	2	Completed	breast carcinoma	ClinicalTrials
AKT1	MK-2206	Serine/threonine-protein kinase AKT inhibitor	2	Terminated	breast carcinoma	ClinicalTrials
AKT1	MK-2206	Serine/threonine-protein kinase AKT inhibitor	2	Completed	adenosquamous lung carcinoma	ClinicalTrials
AKT1	UPROSERTIB	Serine/threonine-protein kinase AKT inhibitor	2	Completed	breast carcinoma	ClinicalTrials
AKT1	MK-2206	Serine/threonine-protein kinase AKT inhibitor	2	Completed	bronchoalveolar adenocarcinoma	ClinicalTrials
AKT1	MK-2206	Serine/threonine-protein kinase AKT inhibitor	2	Completed	diffuse large B-cell lymphoma	ClinicalTrials
AKT1	MK-2206	Serine/threonine-protein kinase AKT inhibitor	2	Terminated	diffuse large B-cell lymphoma	ClinicalTrials
AKT1	CAPIVASERTIB	Serine/threonine-protein kinase AKT inhibitor	2	Terminated	gastric adenocarcinoma	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!

AKT1-Ser124
Cancer	Intensity
BRCA
COAD	-0.707
HGSC	0.707
ccRCC
GBM
HNSC
LUAD
LUSC
non_ccRCC
PDAC
UCEC

AKT1-Ser126
Cancer	Intensity
BRCA
COAD	-0.707
HGSC	0.707
ccRCC
GBM
HNSC
LUAD
LUSC
non_ccRCC
PDAC
UCEC

AKT1-Ser129
Cancer	Intensity
BRCA
COAD	-0.707
HGSC	0.707
ccRCC
GBM
HNSC
LUAD
LUSC
non_ccRCC
PDAC
UCEC

AKT1-Thr448
Cancer	Intensity
BRCA
COAD
HGSC	-0.707
ccRCC
GBM
HNSC
LUAD
LUSC
non_ccRCC
PDAC
UCEC	0.707

AKT1-Thr450
Cancer	Intensity
BRCA
COAD	-0.936
HGSC	-1.526
ccRCC	0.252
GBM	0.594
HNSC
LUAD	0.617
LUSC
non_ccRCC
PDAC
UCEC	0.999

AKT1-Tyr315
Cancer	Intensity
BRCA	0.788
COAD
HGSC
ccRCC
GBM
HNSC
LUAD	-1.125
LUSC	0.336
non_ccRCC
PDAC
UCEC

AKT1S1-Ser183
Cancer	Intensity
BRCA	1.667
COAD	0.891
HGSC	0.725
ccRCC	-1.189
GBM	0.792
HNSC	0.064
LUAD	-0.194
LUSC	-0.266
non_ccRCC	-1.722
PDAC	-0.879
UCEC	0.11

AKT1S1-Ser202
Cancer	Intensity
BRCA	-0.344
COAD	-0.013
HGSC	-2.725
ccRCC	-0.093
GBM	-0.249
HNSC	0.707
LUAD	0.324
LUSC	0.615
non_ccRCC	0.322
PDAC	0.379
UCEC	1.076

AKT1S1-Ser203
Cancer	Intensity
BRCA	-0.189
COAD	0.095
HGSC	-2.902
ccRCC	0.277
GBM	0.142
HNSC	0.479
LUAD	0.265
LUSC	0.603
non_ccRCC	0.04
PDAC	0.419
UCEC	0.771

AKT1S1-Ser211
Cancer	Intensity
BRCA	-1.13
COAD	0.333
HGSC	-2.178
ccRCC	0.627
GBM	0.09
HNSC	1.177
LUAD	-0.47
LUSC	0.383
non_ccRCC
PDAC	0.715
UCEC	0.451

AKT1S1-Ser212
Cancer	Intensity
BRCA	-1.05
COAD	0.546
HGSC	-2.08
ccRCC	-0.197
GBM	0.641
HNSC	1.003
LUAD	-0.628
LUSC	0.311
non_ccRCC
PDAC	0.36
UCEC	1.094

AKT1S1-Ser247
Cancer	Intensity
BRCA
COAD	-1.124
HGSC
ccRCC
GBM	0.791
HNSC	0.334
LUAD
LUSC
non_ccRCC
PDAC
UCEC

AKT1S1-Ser88
Cancer	Intensity
BRCA	-1.265
COAD	-0.583
HGSC
ccRCC	-0.267
GBM	0.344
HNSC	2.36
LUAD	-0.052
LUSC	0.649
non_ccRCC	-0.088
PDAC	-0.187
UCEC	-0.912

AKT1S1-Ser92
Cancer	Intensity
BRCA	-1.122
COAD	-0.689
HGSC
ccRCC	0.068
GBM	-0.037
HNSC	2.235
LUAD	0.28
LUSC	0.221
non_ccRCC	-0.997
PDAC	0.777
UCEC	-0.735

AKT1S1-Thr198
Cancer	Intensity
BRCA
COAD
HGSC
ccRCC	-0.647
GBM
HNSC
LUAD	-0.505
LUSC
non_ccRCC
PDAC
UCEC	1.152

AKT1S1-Thr246
Cancer	Intensity
BRCA
COAD	-0.468
HGSC	0.953
ccRCC
GBM	-1.179
HNSC
LUAD
LUSC
non_ccRCC
PDAC
UCEC	0.694

AKT1S1-Thr90
Cancer	Intensity
BRCA
COAD	0.347
HGSC	-1.784
ccRCC	0.431
GBM
HNSC	0.542
LUAD	0.465
LUSC
non_ccRCC
PDAC
UCEC

AKT1S1-Thr97
Cancer	Intensity
BRCA	1.061
COAD	-1.872
HGSC
ccRCC	0.814
GBM	-0.592
HNSC	0.541
LUAD	0.201
LUSC
non_ccRCC
PDAC
UCEC	-0.152

PTM-Disease Association:

source: PTMD

Residue	Position	State	Disease	Class	PMID
S	473	D	Oral squamous cell carcinoma	Phosphorylation	31889370
S	473	D	Triple-negative breast cancer	Phosphorylation	34077419
S	473	D	Bladder cancer	Phosphorylation	23799035
S	473	D	Pancreatic cancer	Phosphorylation	28363942 ; 15467756
S	473	D	Colon cancer	Phosphorylation	35190555
S	473	D	Head and neck squamous cell carcinoma	Phosphorylation	21281788
S	473	P	Acute myeloid leukemia/acute myelogenous leukemia	Phosphorylation	18056483
S	473	P	Gastric cancer	Phosphorylation	23969493 ; 23440515
S	473	P	Ovarian cancer/carcinoma	Phosphorylation	23877012
S	473	P	Breast cancer	Phosphorylation	36632451
S	473	P	Anaplastic astrocytoma	Phosphorylation	23596468
S	473	P	Esophageal squamous cell carcinoma	Phosphorylation	23510069
S	473	P	Non-small cell lung cancer/carcinoma	Phosphorylation	23091605
S	473	P	Prostate cancer/carcinoma/adenocarcinoma	Phosphorylation	23732709
S	473	U	Pancreatic cancer	Phosphorylation	15467756 ; 28363942
S	473	U	Uveal melanoma	Phosphorylation	34918581
S	473	U	Osteosarcoma	Phosphorylation	34476004
S	473	U	Cancer	Phosphorylation	34767444
S	473	U	Cervical cancer	Phosphorylation	32047568
S	473	U	Acute myeloid leukemia/acute myelogenous leukemia	Phosphorylation	15289327
S	473	U	Breast cancer	Phosphorylation	17545609 ; 12244301 ; 12244301 ; 17545609 ; 21743495 ; 30413706
S	473	U	Chronic lymphocytic leukemia	Phosphorylation	16940331
S	473	U	Esophageal squamous cell carcinoma	Phosphorylation	31897228
S	473	U	Gallbladder cancer	Phosphorylation	33407730
S	473	U	Hepatocellular carcinoma	Phosphorylation	37573318 ; 36348350
S	473	U	Multiple myeloma	Phosphorylation	37781194
S	473	U	Pancreatic cancer/carcinoma/adenocarcinoma	Phosphorylation	15467756 ; 21474066 ; 28363942
S	473	U	Rhabdomyosarcoma	Phosphorylation	17848913
S	473	U	Synovial sarcoma	Phosphorylation	35556229
S	473	U	HER2-positive breast cancer	Phosphorylation	36314765
S	473	U	Thymic carcinoma	Phosphorylation	20597130
S	473	U	Systemic lupus erythematosus	Phosphorylation	23735868 ; 34522717 ; 23735868
S	473	U	Squamous cell carcinoma	Phosphorylation	21795477 ; 37109043
S	473	U	Sjogren's syndrome	Phosphorylation	34948236
S	473	U	Breast cancer/tumor/carcinoma	Phosphorylation	17545609 ; 12244301 ; 22476852
S	473	U	Cancer	Phosphorylation	21795477
S	473	U	Cholangiocarcinoma	Phosphorylation	37752233
S	473	U	Colon cancer/carcinoma	Phosphorylation	22975685
S	473	U	Colorectal cancer	Phosphorylation	37430297
S	473	U	Diabetes mellitus	Phosphorylation	35835217
S	473	U	Glioma	Phosphorylation	33820494
S	473	U	Renal cancer/carcinoma	Phosphorylation	19118035 ; 16247451 ; 12649200
S	473	U	Kidney cancer	Phosphorylation	12649200 ; 12649200 ; 22580611
S	473	U	Liver cancer	Phosphorylation	15684384
S	473	U	Lymphocytic leukemia	Phosphorylation	20576813
S	473	U	Melanoma	Phosphorylation	19996208 ; 12499277 ; 12499277 ; 19996208 ; 12499277
S	473	U	Neuroblastoma	Phosphorylation	17234785
S	473	U	Non-small cell squamous cell lung carcinoma	Phosphorylation	20008839
S	473	U	Obesity	Phosphorylation	35413055
S	473	U	Ovarian cancer	Phosphorylation	15208673
S	473	U	Ovarian epithelial carcinoma	Phosphorylation	32194423
S	473	U	Urethral cancer	Phosphorylation	22975685
S	473	U	Parkinson's disease	Phosphorylation	19800394 ; 19800394 ; 21658387

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