| Id: | acc4915 |
| Group: | 2sens |
| Protein: | Akt |
| Gene Symbol: | Akt1 |
| Protein Id: | P31750 |
| Protein Name: | AKT1_MOUSE |
| PTM: | phosphorylation |
| Site: | Ser473 |
| Site Sequence: | ERRPHFPQFSYSASGTA---- |
| Disease Category: | Cancer |
| Disease: | Melanoma |
| Disease Subtype: | PTEN-deficient / BRAF-mutant |
| Disease Cellline: | |
| Disease Info: | |
| Drug: | selumetinib |
| Drug Info: | "Selumetinib is a selective, orally bioavailable inhibitor of mitogen - activated protein kinase kinases 1 and 2 (MEK1/2). It is used in the treatment of certain types of cancer, such as neurofibromatosis type 1 - related plexiform neurofibromas. " |
| Effect: | inhibit |
| Effect Info: | "SAR260301 selectively inhibits PI3Kbeta, significantly reduces the phosphorylation level of AKT in PTEN-deficient melanoma, thereby blocking the PI3K-AKT pathway signaling, enhancing the sensitivity to BRAF/MEK inhibitors, and the combination therapy shows synergistic antitumor activity." |
| Note: | |
| Score: | 5.0 |
| Pubmed(PMID): | 27196754 |
| Sentence Index: | 27196754_4-5 |
| Sentence: | "Herein, we provide a detailed biological characterization of SAR260301, and show that this compound has outstanding biochemical and cellular selectivity for the PI3Kbeta isoform versus the alpha, delta, and gamma isoforms and a large panel of protein and lipid kinases. We demonstrate that SAR260301 blocks PI3K pathway signaling preferentially in PTEN-deficient human tumor models, and has synergistic antitumor activity when combined with vemurafenib (BRAF inhibitor) or selumetinib (MEK inhibitor) in PTEN-deficient/BRAF-mutated human melanoma tumor models." |
Sequence & Structure:
MNDVAIVKEGWLHKRGEYIKTWRPRYFLLKNDGTFIGYKERPQDVDQRESPLNNFSVAQCQLMKTERPRPNTFIIRCLQWTTVIERTFHVETPEEREEWATAIQTVADGLKRQEEETMDFRSGSPSDNSGAEEMEVSLAKPKHRVTMNEFEYLKLLGKGTFGKVILVKEKATGRYYAMKILKKEVIVAKDEVAHTLTENRVLQNSRHPFLTALKYSFQTHDRLCFVMEYANGGELFFHLSRERVFSEDRARFYGAEIVSALDYLHSEKNVVYRDLKLENLMLDKDGHIKITDFGLCKEGIKDGATMKTFCGTPEYLAPEVLEDNDYGRAVDWWGLGVVMYEMMCGRLPFYNQDHEKLFELILMEEIRFPRTLGPEAKSLLSGLLKKDPTQRLGGGSEDAKEIMQHRFFANIVWQDVYEKKLSPPFKPQVTSETDTRYFDEEFTAQMITITPPDQDDSMECVDSERRPHFPQFSYSASGTA
No data.
No data.
Protein Tractability:
source: Open TargetsNo data.
PTM Intensity:
source: CPTACNo data.
PTM-Disease Association:
source: PTMD| Residue | Position | State | Disease | Class | PMID |
|---|---|---|---|---|---|
| S | 473 | D | Alzheimer's disease | Phosphorylation | 35834993 ; 36843923 |
| S | 473 | D | Colonic inflammation | Phosphorylation | 36735734 |
| S | 473 | D | Diabetes mellitus | Phosphorylation | 17130464 ; 16777975 ; 15033922 ; 15033922 ; 16777975 ; 17130464 ; 35739993 |
| S | 473 | D | Turner syndrome | Phosphorylation | 33910978 |
| S | 473 | U | Cardiomyopathy | Phosphorylation | 35358489 |
| S | 473 | U | Diabetes mellitus | Phosphorylation | 35358489 |
| S | 473 | U | Endometrial cancer/carcinoma | Phosphorylation | 16585156 |
| S | 473 | U | Melanoma | Phosphorylation | 26565903 |
| S | 473 | U | Non-small cell lung cancer | Phosphorylation | 35961388 |
| S | 473 | U | Hepatocellular carcinoma | Phosphorylation | 33500384 |
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: DecryptMNo data.
Function score:
source: funscoRNo data.
