- |||||||||| pictilisib (GDC-0941) / Roche, dactolisib (RTB101) / resTORbio
Journal: Virtual docking screening and QSAR studies to explore AKT and mTOR inhibitors acting on PI3K in cancers. (Pubmed Central) - Jun 11, 2020 The most predicted AKT and mTOR inhibitors present respectively pIC50 activities between 9.26-9.93 and 9.59-9.87. After docking and several comparisons, inhibitors with better predictions showed better affinity and interaction with PI3K compared to pictilisib and dactolisib, so we found that 4 inhibitors of AKT and 14 mTOR inhibitors met the criteria of Lipinski and Veber and could be future drugs.
- |||||||||| Journal: Dual-target inhibitors based on BRD4: Novel therapeutic approaches for cancer. (Pubmed Central) - Jun 11, 2020
In this review, we summarize the molecular interplay between BRD4 and other proteins. Moreover, we summarize the corresponding dual targeting inhibitors, for example HDAC/BRD4 dual inhibitors, PLK1/BRD4 dual inhibitors, PI3K/BRD4 dual inhibitors and so on, in cancer therapy and we make an insight into the structure-activity relationships of these dual-target agents.
- |||||||||| sirolimus / Generic mfg.
Review, Journal: PI3K pathway defects leading to immunodeficiency and immune dysregulation. (Pubmed Central) - Jun 10, 2020 Although a small group of patients reported to underactivate PI3Kδ show predominantly humoral defects and autoimmune features, more than 200 patients have been described with overactivation of PI3Kδ, presenting with a much more complex phenotype of combined immunodeficiency and immune dysregulation. The clinical and immunologic characterization, as well as current pathophysiologic understanding and specific therapies for PI3K pathway defects leading to immunodeficiency and immune dysregulation, are reviewed here.
- |||||||||| quercetin (LY294002) / Eli Lilly
Journal: Apelin shorten QT interval by inhibiting Kir2.1/I via a PI3K way in acute myocardial infarction. (Pubmed Central) - Jun 10, 2020 In cultured neonatal mouse cardiomyocytes, Apelin (1 μmol/L) restored hypoxia-induced Kir2.1 down-regulation, which was abolished by IP3K inhibitor LY-294002...These results showed that Apelin enhanced I/Kir2.1 currents via IP3K pathway as by rescue ischemia- and hypoxia-induced RMP depolarization and prolongation of QT interval, which may prevent or cure acute ischemic-mediated arrhythmias. This study brings new information to anti-arrhythmic theories and provides a potential target for the clinical management of acute ischemia-related arrhythmias.
- |||||||||| dactinomycin / Generic mfg.
Journal: BMP9 directly induces rapid GSK3-β phosphorylation in a Wnt-independent manner through class I PI3K-Akt axis in osteoblasts. (Pubmed Central) - Jun 10, 2020 Furthermore, BMP9-induced GSK3-β phosphorylation was not inhibited by pretreatment with actinomycin D, cycloheximide, or Brefeldin A, indicating it is independent of Wnt protein secretion...Notably, BMP9-induced GSK3-β phosphorylation was inhibited by small interfering RNA against endoglin and GIPC PDZ domain-containing family, member 1. Taken together, our present findings have indicated that BMP9 directly activates GSK3β-β-catenin signaling pathway through class I PI3K-Akt Axis in osteoblasts, which may be essential for the potent osteoinductive activity of BMP9.-Eiraku, N., Chiba, N., Nakamura, T., Amir, M. S., Seong, C.-H., Ohnishi, T., Kusuyama, J., Noguchi, K., Matsuguchi, T. BMP9 directly induces rapid GSK3-β phosphorylation in a Wnt-independent manner through class I PI3K-Akt axis in osteoblasts.
- |||||||||| Journal: APLNR is involved in ATRA-induced growth inhibition of nasopharyngeal carcinoma and may suppress EMT through PI3K-Akt-mTOR signaling. (Pubmed Central) - Jun 10, 2020
Our study further demonstrated that low expression of APLNR promoted EMT in NPC cells by activating the PI3K-protein kinase B-mammalian target of rapamycin signaling pathway. Taken together, our data suggest that APLNR could potentially predict prognosis for patients with NPC and inhibit proliferation, migration, invasion, and EMT in nasopharyngeal cancer cells.-Liu, Y., Liu, Q., Chen, S., Liu, Y., Huang, Y., Chen, P., Li, X., Gao, G., Xu, K., Fan, S., Zeng, Z., Xiong, W., Tan, M., Li, G., Zhang, W. APLNR is involved in ATRA-induced growth inhibition of nasopharyngeal carcinoma and may suppress EMT through PI3K-Akt-mTOR signaling.
- |||||||||| Journal: Dopamine D receptor protected against hyperglycemia-induced endothelial dysfunction via PI3K /eNOS pathway. (Pubmed Central) - Jun 10, 2020
More importantly, the expression level of D receptor was also dramatically down-regulated in the arterial endothelium of rats with streptozotocin-(STZ)-induced diabetes, and the STZ-induced impairment of acetylcholine-induced vasodilation was reversed by activation of D receptor. In conclusion, our results indicated that dopamine D receptor protected against hyperglycemia-induced endothelial dysfunction via the PI3K/eNOS pathway, which may provide a novel strategy in the treatment of diabetes.
- |||||||||| quercetin (LY294002) / Eli Lilly, U0126 / Promega
Preclinical, Journal: Leukotriene B induces proliferation of rat pulmonary arterial smooth muscle cells via modulating GSK-3β/β-catenin pathway. (Pubmed Central) - Jun 9, 2020 In addition, inactivation or lack of GSK-3β up-regulated β-catenin and cyclin D1 in PASMCs. Taken together, our study indicates that activation of PI3K/Akt and ERK1/2 pathways mediate LTB-induced PASMCs proliferation by modulating GSK-3β/β-catenin/cyclin D1 axis and suggests that targeting this pathway might have potential value in alleviating vascular remodeling and benefit PAH.
- |||||||||| quercetin (LY294002) / Eli Lilly
Journal, IO Biomarker: Sodium Tanshinone II Sulfonate A Ameliorates Hypoxia-Induced Pulmonary Hypertension. (Pubmed Central) - Jun 9, 2020 In addition, hypoxia-induced increases in PAP, cardiac hypertrophy, and lung expression of the proteins PI3K/Akt/mTOR/autophagy pathway were partially reversed by treatment with LY294002. STS alleviates hypoxia-induced PH by promoting apoptosis, inhibiting PI3K/AKT/mTOR pathway, up-regulating autophagy, and inhibiting inflammatory responses.
- |||||||||| Clinical, Journal: Clinical significance of PI3K/Akt/mTOR signaling in gastric carcinoma. (Pubmed Central) - Jun 9, 2020
Alterations of mTOR pathway protein expression are associated with reduced survival in gastric cancer. Significance was noted in the association of pS6 positivity and eIF4E positivity e with reduced survival in univariate analysis and the association of PTEN loss and reduced DFS in univariate analysis as well as multivariate analysis for DFS.
- |||||||||| cisplatin / Generic mfg.
Journal: MARK2 enhances cisplatin resistance via PI3K/AKT/NF-κB signaling pathway in osteosarcoma cells. (Pubmed Central) - Jun 9, 2020 Mechanistically, MARK2 overexpression enhanced P-glycoprotein expression and decreased cell apoptosis through PI3K/AKT/NF-κB signaling pathway activation, resulting in cisplatin resistance. Our results suggest that high MARK2 expression can enhance cisplatin resistance in osteosarcoma cells, supporting the potential of MARK2 as a new therapeutic target and biomarker for predicting cisplatin resistance in osteosarcoma.
- |||||||||| Piqray (alpelisib) / Novartis, taselisib (GDC-0032) / Roche, buparlisib (BKM120) / Novartis, Adlai Nortye
Biomarker, Journal: Exploring Biomarkers of Phosphoinositide 3-Kinase Pathway Activation in the Treatment of Hormone Receptor Positive, Human Epidermal Growth Receptor 2 Negative Advanced Breast Cancer. (Pubmed Central) - Jun 8, 2020 Combining buparlisib, a pan-PI3K-targeted agent, with ET demonstrated modest clinical benefits in patients with aromatase inhibitor-resistant, HR+, human epidermal growth receptor 2 negative (HER2-) ABC in two phase III trials...In early clinical trials, promising disease control benefits were demonstrated with the PI3K isoform-selective inhibitors alpelisib and taselisib in patients with PIK3CA-mutated HR+, HER2- ABC...Early-phase studies have confirmed that patients with PIK3CA mutations respond best to PI3Kα-isoform inhibition. Ongoing phase III trials will provide further data regarding the efficacy and safety of PI3K inhibitors in patients with different biomarker profiles.
- |||||||||| Garamycin (gentamicin sulfate) / Generic mfg.
Journal: Pasireotide protects mammalian cochlear hair cells from gentamicin ototoxicity by activating the PI3K-Akt pathway. (Pubmed Central) - Jun 8, 2020 Auditory brainstem response analysis confirmed the protective effect of pasireotide, and we found a significant threshold shift at all measured frequencies (4, 8, 16, 24, and 32 kHz). Together, these findings indicate that pasireotide is a novel otoprotective peptide acting via the PI3K-Akt pathway and may be of therapeutic value for HC protection from ototoxic insults.
- |||||||||| Ossirene (AS101) / Cassiopea, Feramda
Journal: Endometriosis triggers excessive activation of primordial follicles via PI3K-PTEN-Akt-Foxo3 pathway. (Pubmed Central) - Jun 8, 2020 The current study describes the excessive activation of primordial follicles and the role of the PI3K-PTEN-Akt-Foxo3 pathway in the reduction of ovarian reserve associated with endometriosis. Our results suggest that a PI3K-PTEN-Akt inhibitor should be considered for further investigation as promising medicines for the prevention of the ovarian reserve reduction in endometriosis patients.
- |||||||||| Preclinical, Journal, IO Biomarker: Protective Effect Of Vasicine Against Myocardial Infarction In Rats Via Modulation Of Oxidative Stress, Inflammation, And The PI3K/Akt Pathway. (Pubmed Central) - Jun 8, 2020
Furthermore, VAS suppressed apoptosis when tested on animals suffering from ISO-induced MI, by decreasing the expression of cleaved Caspase-3 and Bax while increasing the expression of Bcl-2. In conclusion, vasicine has a protective effect against MI in vivo, through inhibiting oxidative stress, inflammation and excessive autophagy, to suppress apoptosis via activation of the PI3K/Akt/mTOR signaling pathway.
- |||||||||| Review, Journal: Targeting PI3K/AKT/mTOR-mediated autophagy for tumor therapy. (Pubmed Central) - Jun 8, 2020
Targeting PI3K/AKT/mTOR-mediated autophagy is an important therapeutic strategy for a variety of tumors, and plays important roles in enhancing the chemosensitivity of tumor cells and avoiding drug resistance. Therefore, we summarized the roles of PI3K/AKT/mTOR-mediated autophagy in tumorigenesis, progression, and drug resistance of tumors, which may be utilized to design preferably therapeutic strategies for various tumors.
- |||||||||| Journal, PARP Biomarker, IO Biomarker: Methyl lucidone induces apoptosis and G/M phase arrest via the PI3K/Akt/NF-κB pathway in ovarian cancer cells. (Pubmed Central) - Jun 8, 2020
Interestingly, ML also inhibited the activity of PI3K/Akt and NF-κB.Discussion and ML caused G/M phase arrest and apoptosis in ovarian cancer cells by activating intrinsic apoptotic pathways and suppressing the PI3K/Akt survival pathway. ML may be a potential anticancer agent to suppress ovarian cancer proliferation; thus, to improve the survival rate of cancer patients.
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