Akt2 (myr)
- Known as:
- Akt2 (myr)
- Catalog number:
- 000042A
- Product Quantity:
- 250ul
- Category:
- -
- Supplier:
- ABM
- Gene target:
- Akt2 (myr)
Related genes to: Akt2 (myr)
- Gene:
- AKT2 NIH gene
- Name:
- AKT serine/threonine kinase 2
- Previous symbol:
- -
- Synonyms:
- -
- Chromosome:
- 19q13.2
- Locus Type:
- gene with protein product
- Date approved:
- 1992-11-05
- Date modifiied:
- 2016-10-05
- Gene:
- MYO1B NIH gene
- Name:
- myosin IB
- Previous symbol:
- -
- Synonyms:
- myr1
- Chromosome:
- 2q32.3
- Locus Type:
- gene with protein product
- Date approved:
- 1996-04-04
- Date modifiied:
- 2016-10-05
- Gene:
- MYO1C NIH gene
- Name:
- myosin IC
- Previous symbol:
- -
- Synonyms:
- myr2
- Chromosome:
- 17p13.3
- Locus Type:
- gene with protein product
- Date approved:
- 1996-04-04
- Date modifiied:
- 2014-11-19
- Gene:
- MYO1D NIH gene
- Name:
- myosin ID
- Previous symbol:
- -
- Synonyms:
- KIAA0727, myr4, PPP1R108
- Chromosome:
- 17q11.2
- Locus Type:
- gene with protein product
- Date approved:
- 1996-04-04
- Date modifiied:
- 2015-09-04
Related products to: Akt2 (myr)
Related articles to: Akt2 (myr)
- Non-small-cell lung cancer (NSCLC), the predominant histological subtype accounting for more than 85% of lung cancer cases, remains the leading cause of cancer-related mortality worldwide. Despite the clinical advances afforded by targeted therapies, the frequent emergence of oncogenic driver mutations drives drug resistance and therapeutic failure, underscoring the critical need for novel molecular targets and alternative therapeutic strategies. AKT1, a serine/threonine kinase and central effector of the PI3K/AKT/mTOR signaling cascade, regulates key oncogenic processes including cell growth, survival, proliferation, and apoptotic evasion, and dysregulated hyperactivation is observed in 30-75% of NSCLC cases. Selective allosteric inhibition of AKT1, which targets the unique PH-kinase domain interface rather than the highly conserved ATP-binding pocket, has emerged as a more isoform-specific and therapeutically advantageous strategy compared with pan-AKT or ATP-competitive inhibition. In the present study, a ChemDiv AKT1-targeted compound library comprising 14,043 small molecules was subjected to hierarchical structure-based virtual screening using sequential high-throughput virtual screening (HTVS), standard precision (SP), and extra precision (XP) docking protocols, followed by binding free energy calculations using the MM-GBSA method. The top XP-ranked compounds, compound 1 (docking score: -11.771 kcal/mol), compound 2 (-11.428 kcal/mol), and compound 3 (-11.167 kcal/mol), achieved more favourable XP docking scores at the AKT1 allosteric site (PDB ID: 3O96) than established pan-AKT inhibitors, including MK-2206, miransertib, Bay1125976, and vevorisertib, although MM-GBSA rescoring did not reproduce this ordering. Comparative docking against the allosteric sites of AKT2 and AKT3 revealed a consistent preference for AKT1 across all three compounds, with a magnitude closely comparable to that of the reference allosteric ligand Inhibitor VIII, whose experimentally determined isoform rank order the protocol reproduced. Comprehensive 300-ns all-atom molecular dynamics (MD) analysis, encompassing RMSD and RMSF profiling, principal component analysis, dynamic cross-correlation matrix analysis, free energy landscape evaluation, and protein-ligand contact profiling, consistently demonstrated that compounds 1 and 2 maintain stable, high-affinity interactions with AKT1, exhibiting persistent engagement with the critical allosteric residues Trp80 and Tyr272 throughout the simulation trajectory. Furthermore, both compounds exhibited favourable pharmacokinetic profiles with predicted human oral absorption values over 80%, supporting their potential for preclinical development. - Source: PubMed
Publication date: 2026/09/08
Das RajuSultana ArminDas KantuChowdhury DipannitaChoi Seong WooWoo Joohan - Macrophage immune dysregulation in sepsis contributes to secondary infections and poor outcomes. Immunosuppression, a key feature of this dysregulation, has been linked to the acquisition of cellular senescence-like features in cancer. However, the mechanistic connection between immune tolerance, a well-established cellular model of immunosuppression, and macrophage senescence remains poorly understood. Here, using an in vitro model of lipopolysaccharide (LPS)-induced tolerance, we found that immune-tolerant macrophages acquired a senescent phenotype. Unexpectedly, nicotinamide phosphoribosyltransferase (NAMPT) mRNA and protein levels were markedly upregulated in tolerant macrophages despite profound suppression of MYC proto-oncogene (MYC), a canonical transcriptional regulator of NAMPT. Mechanistically, this paradoxical accumulation of NAMPT was driven by reduced expression of the RNA helicase DEAD-box helicase 6 (DDX6), thereby enhancing NAMPT mRNA stability. However, increased NAMPT abundance was uncoupled from its enzymatic activity owing to diminished AKT serine/threonine kinase 2 (AKT2)-mediated phosphorylation. Treatment with SC79, a pan-AKT activator, restored NAMPT phosphorylation and activity, attenuated senescence-associated markers, and enhanced bactericidal function in tolerant macrophages. In a murine model of sepsis, alveolar macrophages similarly exhibited reduced DDX6 and AKT2 expression, together with elevated NAMPT abundance, corroborating the in vitro findings. Collectively, these results identify a dual-layer regulatory mechanism in which DDX6 controls NAMPT abundance, whereas AKT2 dictates its activity. The uncoupling of NAMPT abundance from its enzymatic activity drives senescence during immune tolerance, identifying AKT2-NAMPT as a potential therapeutic axis to restore immune competence in sepsis. - Source: PubMed
Publication date: 2026/09/10
Li QilanHe MeiShi PeichiLi XuefengXu ZiliYao LuDu XinyiSong ChaoyingLi ChangJiang LangYang XiaoboZhang DingyuXu JiqianShang You - Aging, as an inevitable biological process, is an inevitable process of multisystem functional decline, with cellular senescence being one of its hallmarks. Although total saponins from (TSG) offer health benefits, its precise anti-aging mechanisms have not been fully elucidated. - Source: PubMed
Publication date: 2026/07/06
Tan Yu-JingJin Wen-QiWang JingWang HuiLou Ting-TingSun Li-WeiLiu Fang-BingZhang Shuai - The Akt family of serine/threonine kinases plays a crucial role in various cellular processes, including proliferation, survival, and metabolism. Three Akt isoforms (Akt1, Akt2, and Akt3) have distinct physiological roles, and while individual isoform dysregulation is disease-linked, unselective Akt inhibition leads to side effects. Here, we report the development of selective covalent-allosteric Akt inhibitors (CAAIs) targeting Akt2 and Akt3 while sparing Akt1. Guided by protein x-ray crystallography and molecular modeling, key structural differences within the allosteric pockets of the isoforms were identified and exploited in a structure-based design strategy. By stabilizing the inactive kinase conformation, CAAIs overcome the intrinsic selectivity limitations of ATP-competitive inhibitors. After biological characterization, the pyrazole-containing inhibitors emerged as the most potent and selective Akt2 inhibitors, while inhibitors with pyridines as an isoform-selective element were predominantly targeting Akt3 selectively. Importantly, these new inhibitors were also evaluated in patient-derived colorectal cancer organoids. Co-crystal structures of inhibitors bound to an engineered construct mimicking the Akt2 allosteric pocket elucidated the molecular basis of isoform selectivity, guiding further optimization. This work not only establishes a framework for the development of isoform-selective therapeutics but also highlights the potential for unraveling isoform-specific functions in signaling pathways relevant to cancer biology. - Source: PubMed
Publication date: 2026/09/07
D'Angelo Giovanni DaniloPervanidis Kosmas AlexandrosAthanasiadis IoannisLukianchikov VladimirScrima AndreaDepta LauraStier SaraMüller Matthias PFarin Henner FQuambusch LenaRauh Daniel - AKT (protein kinase B, PKB) coordinates the balance between anabolic and catabolic signaling in skeletal muscle through distinct ubiquitin chain types. Some E3 ubiquitin ligases (E3s) and deubiquitinases (DUBs) form stable binary complexes via non-catalytic interfaces, adding a regulatory layer unavailable to either enzyme alone. This mechanistic synthesis review presents a systematic literature analysis (inception to May 2026; 26 eligible studies). It identified four E3-DUB pairs proposed to regulate AKT in skeletal muscle. These are TRAF6-CYLD (plasma-membrane K63-ubiquitination), MUL1-USP9X (mitochondrial K48-ubiquitination of AKT2), CHIP-UCH37 (proteasome-proximal quality control), and SCF-Skp2-USP37 (PHLPP1/2-dependent control of AKT Ser473 phosphorylation). All four interfaces are structurally separate from the catalytic sites and are regulated by upstream kinase phosphorylation. Evidence for the four pairs is markedly uneven. TRAF6-CYLD is supported by endogenous co-immunoprecipitation and functional data in muscle models. CHIP and UCH37 each act on AKT-related substrates independently and are individually well documented, but a direct CHIP-UCH37 interaction has not itself been demonstrated. SCF-Skp2-USP37 interaction data rest on a real but non-muscle direct interaction, whereas MUL1-USP9X has no reported direct interaction at all; CHIP-UCH37, SCF-Skp2-USP37, and MUL1-USP9X are therefore all presented as testable hypotheses of varying strength. In chronic atrophy, available data are consistent with disruption of these complexes contributing to AKT suppression through parallel, largely independent mechanisms. However, simultaneous disruption of all four has not been demonstrated in a single system. Available gene expression and protein datasets from sarcopenic muscle broadly support these predictions, though direct experimental validation in human tissue remains pending. This complex-centric framework recasts AKT ubiquitination as an integrated regulatory framework. Each structurally autonomous interface may represent a potentially distinct target for muscle-wasting conditions that currently lack approved therapies. - Source: PubMed
Dabur Rajesh