BKM120 (Buparlisib) is one of the most advanced phosphoinositide 3-kinase (PI3K) inhibitors for the treatment of cancer, but it interferes as an off-target effect with microtubule polymerization. Here, we developed two chemical derivatives that differ fr
Finally, MD simulations were performed to elucidate the important interactions between copanlisib and different PI3K subtypes, and highlight the key residues for tight-binding inhibitors. The present study uncovered the principal mechanism of copanlisib's action on PI3K at the theoretical level, and...
As shown in Figure 6a, most of the PI3K inhibitors reduced the level of β-TrCP1 in these cells. Notably, PI3K inhibitors, which are known to inhibit preferentially PI3Kα, markedly reduced the β-TrCP1 protein, whereas PI3K inhibitors (TGX221, TG100-115 and IC-87114) specific to other ...
MicroRNA 介导 PTEN 下调:头颈部鳞状细胞癌对 PI3Kα 抑制剂获得性耐药的新机制 《Drug Resistance Updates》:MicroRNA-mediated PTEN downregulation as a novel non-genetic mechanism of acquired resistance to PI3Kα inhibitors of head & neck squamous cell carcinoma 编辑推荐: 头颈部鳞状细胞癌(HNSCC)对 PI3K...
Davies SP, Reddy H, Caivano M, Cohen P. Specificity and mechanism of action of some commonly used protein kinase inhibitors.Biochem J2000;351: 95–105. Google Scholar Schultz RM, Merriman RL, Andis SL,et al.In vitroandin vivoantitumor activity of the phosphatidylinositol-3-kinase inhibitor,...
The introduction of combined conventional cytostatics and pathway-specific inhibitors has opened new treatment options for several cancer types including hematologic neoplasia such as leukaemias. As the detailed understanding of the combination-induced molecular effects is often lacking, the identification of...
Understanding how small molecule inhibitors of PI3Kα affect essential macromolecular interactions like membrane binding is necessary for a complete definition of the mechanism of action of ATP binding site inhibitors and the discovery of compounds with specific mechanisms of action. In this study we ...
Novel pan PI3K inhibitor-induced apoptosis in APL cells correlates with suppression of telomerase: An emerging mechanism of action of BKM120. Int J Biochem Cell Biol. 2017 Oct;91(Pt A):1–8. doi: 10.1016/j.biocel.2017.08.009. Bashash D, Safaroghli-Azar A, Dadashi M, Safa M, Momeny ...
Despite these advances, novel effective therapies for prostate cancer based on mechanism of action studies are urgently needed. Receptor tyrosine kinases (RTKs) have emerged as new drugable targets for treatment of several human solid and hematological malignancies [10, 11]. For example, imatinib ...
In conclusion, integration of transcriptomic and proteomic data indicate that MSTN inactivation could promote survival and resistance to apoptosis in muscle through the PI3K/Akt/GSK-3β survival pathway and through a mechanism that involves regulation of pro- and anti-apoptotic factors. A combination ...