Akt
The Ser/Thr kinase AKT, also known as protein kinase B (PKB) has been the focus of tens of thousands of studies in diverse fields of biology and medicine. Activation of PI3K by extracellular stimuli results in activation of AKT in virtually all cells and tissues. The canonical pathway leading to AKT activation is initiated by the stimulation of receptor tyrosine kinases (RTK) or G protein coupled receptors (GPCR) leading to plasma membrane recruitment and activation of one or more isoforms of the class I PI3K family.Activation of PI3K results in the phosphorylation of two key residues on AKT1, T308 in the activation, or T-loop, of the catalytic protein kinase core, and S473 in a C-terminal hydrophobic motif. Phosphorylation of both residues is required for maximal activation of the kinase.
Regulation also occurs on corresponding residues in AKT2 (T309 and S474) and AKT3 (T305 and S472). In addition to signal termination by lipid phosphatases such as PTEN and INPP4B, two critical protein phosphatases function to directly inactivate AKT. There have been many advances in our knowledge of the upstream regulatory inputs into AKT, key multifunctional downstream signaling nodes (GSK3, FoxO, mTORC1), which greatly expand the functional repertoire of Akt, and the complex circuitry of this dynamically branching and looping signaling network that is ubiquitous to nearly every cell in our body. Mouse and human genetic studies have also revealed physiological roles for the AKT network in nearly every organ system. The comprehension of AKT regulation and functions is particularly important given the consequences of AKT dysfunction in diverse pathological settings, including developmental and overgrowth syndromes, cancer, cardiovascular disease, insulin resistance and type-2 diabetes, inflammatory and autoimmune disorders, and neurological disorders.
References
1.Manning BD, et al. Cell. 2017 Apr 20;169(3):381-405. doi: 10.1016/j.cell.2017.04.001.
Regulation also occurs on corresponding residues in AKT2 (T309 and S474) and AKT3 (T305 and S472). In addition to signal termination by lipid phosphatases such as PTEN and INPP4B, two critical protein phosphatases function to directly inactivate AKT. There have been many advances in our knowledge of the upstream regulatory inputs into AKT, key multifunctional downstream signaling nodes (GSK3, FoxO, mTORC1), which greatly expand the functional repertoire of Akt, and the complex circuitry of this dynamically branching and looping signaling network that is ubiquitous to nearly every cell in our body. Mouse and human genetic studies have also revealed physiological roles for the AKT network in nearly every organ system. The comprehension of AKT regulation and functions is particularly important given the consequences of AKT dysfunction in diverse pathological settings, including developmental and overgrowth syndromes, cancer, cardiovascular disease, insulin resistance and type-2 diabetes, inflammatory and autoimmune disorders, and neurological disorders.
References
1.Manning BD, et al. Cell. 2017 Apr 20;169(3):381-405. doi: 10.1016/j.cell.2017.04.001.
Cytoskeleton/Cell Adhesion Molecules
Akt
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YS-67
产品货号 : M37328
cas no: 2761327-15-3
YS-67 是一种有效的 EGFR 抑制剂,其 IC 50 为 5.2 nM。YS-67 显著抑制 p-EGFR 和 p-AKT。YS-67 抑制 A549、PC-9 和 A431 细胞的增殖,IC 50 分别为 4.1、0.5 和 2.1 μM。 -
Xentuzumab
产品货号 : M36725
cas no: 1417158-65-6
Xentuzumab (Anti-Human IGF1 and IGF2 Recombinant Antibody; BI836845) 是重组的人源化单克隆抗体,靶向 IGF 配体 IGF1 和 IGF2。Xentuzumab 抑制 IGF1 和 IGF2 的生长促进信号,抑制 AKT 的激活。 -
Akt3 degrader 1
产品货号 : M36618
cas no: 2836342-69-7
Akt3 degrader 1 (化合物 12l) 是一种选择性的 Akt3 降解剂,能克服 Osimertinib (HY-15772) 诱导的 H1975OR NSCLC 细胞的抗性。Akt3 degrader 1 还具有抗增殖活性,能显著抑制小鼠体内肿瘤的生长。Akt3 degrader 1 可用于耐药性非小细胞肺癌的研究。 -
ZINC00640089
产品货号 : M36484
cas no: 667880-11-7
ZINC00640089 是一种特异性的脂质运载蛋白-2 (LCN2) 抑制剂。ZINC00640089 能抑制细胞增殖、细胞活力并降低 SUM149 细胞的 AKT 磷酸化水平。ZINC00640089 对炎症性乳腺癌 (IBC) 具有较好的研究潜力。 -
Hu7691 free base
产品货号 : M35148
cas no: 2241232-43-7
Hu7691 free base 是一种具有口服活性的,选择性 Akt 抑制剂,对 Akt1、Akt2 和 Akt3 的 IC50 分别为 4.0 nM、97.5 nM、28 nM。Hu7691 free base 抑制肿瘤生长并降低小鼠的皮肤毒性。