Id: acc0490
Group: 1sens
Protein: AKT
Gene Symbol: AKT1
Protein Id: P31749
Protein Name: AKT1_HUMAN
PTM: phosphorylation
Site: Thr308
Site Sequence: GIKDGATMKTFCGTPEYLAPE
Disease Category: Cancer
Disease: Hepatocellular Carcinoma
Disease Subtype:
Disease Cellline: HepG2
Disease Info:
Drug: cabozantinib + CT-707
Drug Info: "Cabozantinib is a multi-targeted tyrosine kinase inhibitor that inhibits MET, VEGFR, RET, AXL, and other kinases, approved for the treatment of progressive metastatic medullary thyroid cancer, advanced renal cell carcinoma, and hepatocellular carcinoma. CT-707 is a multi-target inhibitor of ALK, FAK, PYK2, and IGF1R, currently under clinical investigation for advanced pancreatic cancer in combination therapy. "
Effect: modulate
Effect Info: The combination of cabozantinib and CT - 707 induces enhanced apoptosis and exerts synergistic inhibition on the activated AKT signaling pathway.
Note:
Score: 4.0
Pubmed(PMID): 27638856
Sentence Index:
Sentence:

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
AKT1-Thr308
Cancer Intensity
BRCA
COAD
HGSC
ccRCC
GBM
HNSC
LUAD
LUSC
non_ccRCC
PDAC
UCEC

PTM-Disease Association:

source: PTMD
Residue Position State Disease Class PMID
T 308 D Ovarian cancer/carcinoma Phosphorylation 20153512
T 308 D Type 2 diabetes Phosphorylation 15919790 ;  15919790
T 308 D Head and neck squamous cell carcinoma Phosphorylation 21281788
T 308 D Diabetes mellitus Phosphorylation 17272402 ;  20938636 ;  15919790
T 308 P Non-small cell lung cancer/carcinoma Phosphorylation 23091605
T 308 U Chronic lymphocytic leukemia Phosphorylation 16940331
T 308 U Melanoma Phosphorylation 19996208
T 308 U Multiple myeloma Phosphorylation 37781194
T 308 U Neuroblastoma Phosphorylation 17234785
T 308 U Pancreatic cancer/carcinoma/adenocarcinoma Phosphorylation 26676747
T 308 U Rhabdomyosarcoma Phosphorylation 17848913
T 308 U Breast cancer Phosphorylation 33571243
T 308 U Acute myeloid leukemia/acute myelogenous leukemia Phosphorylation 12750723
T 308 U Cholangiocarcinoma Phosphorylation 37752233
T 308 U Lymphocytic leukemia Phosphorylation 20576813
T 308 U Obesity Phosphorylation 35413055
T 308 U Sjogren's syndrome Phosphorylation 34948236
T 308 U Endometrial cancer Phosphorylation 35253622
T 308 U Esophageal squamous cell carcinoma Phosphorylation 36995521

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: