- |||||||||| buparlisib (AN2025) / Adlai Nortye
Trial termination: Neoadjuvant BKM120 in High-risk Prostate Cancer (clinicaltrials.gov) - Jan 13, 2021 P2, N=11, Terminated, Thus, we identified a novel non-cell autonomous neuroprotective signaling cascade mediated through PI3K that requires recruitment of ZC3H14 and may present a promising strategy to promote astrocyte-secreted pro-survival signals. Completed --> Terminated; Lack of Accrual
- |||||||||| Journal: Nrf2 activation through the PI3K/GSK-3 axis protects neuronal cells from Aβ-mediated oxidative and metabolic damage. (Pubmed Central) - Jan 13, 2021
Results support the use of copanlisib 0.8 mg/kg (or flat-dose equivalent of 60 mg) in solid tumors and lymphoma, and provide a biomarker hypothesis for studies of copanlisib combined with immune checkpoint inhibitors (NCT03711058). Our study provides insights into the complex molecular mechanisms triggered by oligAβ which profoundly affect mitochondrial performance and argues for the inclusion of small molecules targeting the PI3K/GSK-3 axis and Nrf2-mediated pathways as part of the current or future combinatorial therapies.
- |||||||||| Journal: MiR-489 inhibited the development of gastric cancer via regulating HDAC7 and PI3K/AKT pathway. (Pubmed Central) - Jan 13, 2021
Our study provides insights into the complex molecular mechanisms triggered by oligAβ which profoundly affect mitochondrial performance and argues for the inclusion of small molecules targeting the PI3K/GSK-3 axis and Nrf2-mediated pathways as part of the current or future combinatorial therapies. Correctively, miR-489 played as a tumor suppressor in GC cell growth by targeting HDAC7, and miR-489 might function as a novel biomarker for diagnosis or therapeutic targets of human GC.
- |||||||||| samotolisib (LY3023414) / Eli Lilly
Journal: Overexpression of ABCB1 and ABCG2 contributes to reduced efficacy of the PI3K/mTOR inhibitor samotolisib (LY3023414) in cancer cell lines. (Pubmed Central) - Jan 12, 2021 Furthermore, stimulatory effect of LY3023414 on the ATPase activity of ABCB1 and ABCG2, as well as in silico molecular docking analysis of LY3023414 binding to the substrate-binding pockets of these transporters provided additional insight into the manner in which LY3023414 interacts with both transporters. In conclusion, we report that LY3023414 is a substrate for ABCB1 and ABCG2 transporters implicating their role in the development of resistance to LY3023414, which can have substantial clinical implications and should be further investigated.
- |||||||||| Journal: 2,5-Hexanedione influences primordial follicular development in cultured neonatal mouse ovaries by interfering with the PI3K signaling pathway via miR-214-3p. (Pubmed Central) - Jan 12, 2021
In the present study, whole neonatal mouse ovaries were exposed to 2,5-HD in vitro and then assessed for progesterone levels to determine the effects of this compound on ovary function...Furthermore, the effects of 2,5-HD on the gene expression of the PI3K/AKT/FOXO3 and follicular development were blocked by 740Y-P (a PI3K activator), miR-214-3p was abnormally expressed, and luciferase reporter assay results demonstrated that the 3' untranslated region of PI3K was a direct target of miR-214-3p. Overall, the results of the present study indicate that 2,5-HD exposure inhibits follicular development, and the underlying mechanism may involve interference with miR-214-3p-mediated regulation of the PI3K signaling pathway.
- |||||||||| Journal: Role of the PI3K/Akt pathway in cadmium induced malignant transformation of normal prostate epithelial cells. (Pubmed Central) - Jan 12, 2021
Taken together, our study reveals that the PI3K/Akt signaling is one of the main molecular pathways involved in Cd-driven transformation of normal prostate epithelial cells to malignant form. Understanding the molecular mechanisms involved in the Cd-driven malignant transformation of normal prostate cells will provide a significant insight to develop better therapeutic strategies for Cd-induced prostate cancer.
- |||||||||| Journal, Cancer stem cells: A Novel Therapeutic Approach for Colorectal Cancer Stem Cells: Blocking the PI3K/Akt Signaling Axis With Caffeic Acid. (Pubmed Central) - Jan 12, 2021
In addition, we also revealed that PI3K/Akt signaling may be linked to multiple colorectal CSC-associated characteristics, such as radio-resistance, stem-like property, and tumorigenic potential. To the best of our knowledge, this is the first study demonstrating that caffeic acid effectively targets colorectal CSC populations by inhibiting the growth and/or self-renewal capacity of colorectal CSCs through PI3K/Akt signaling in vitro and in vivo.
- |||||||||| AG-1296 - Friedrich / Schiller University of Jena, Wuhan University, Zhejiang University
Journal: Endothelial progenitor cells promote viability and nerve regenerative ability of mesenchymal stem cells through PDGF-BB/PDGFR-β signaling. (Pubmed Central) - Jan 9, 2021 EPCs-derived paracrine factors containing PDGF-BB (platelet-derived growth factor) were detected, and MSCs were pre-treated with PDGF-BB, while co-MSCs were pre-treated with PDGFR inhibitor AG1296...To our knowledge, our study first demonstrates that EPCs promote viability and potential nerve regenerative ability of MSCs through PDGF-BB/PDGFR-β signaling and its downstream PI3K/Akt and MEK/Erk pathways. mTOR acts as a co-mediator in PI3K/Akt and MEK/Erk pathways.
- |||||||||| Preclinical, Journal: Molecular determinants of response to PI3K/akt/mTOR and KRAS pathways inhibitors in NSCLC cell lines. (Pubmed Central) - Jan 9, 2021
Interestingly, we found that p53 mutational status separates the cell lines according to their sensitivity to PI3K pathway inhibitors treatments. The alterations considered in the PI3K/akt/mTOR and in the KRAS/MEK/ERK pathways in the different NSCLC cell lines are not sufficient to drive treatment choice but rather p53 status is a potential biomarker for the activity of this class of drugs.
- |||||||||| quercetin (LY294002) / Eli Lilly
Journal: Neuroprotective effects of mGluR5 activation through the PI3K/Akt pathway and the molecular switch of AMPA receptors. (Pubmed Central) - Jan 8, 2021 These protective effects of DHPG and VU0092273 were prevented by inhibition of PI3K/Akt pathway by LY294002...Furthermore, immunohistochemical assays confirmed the neuroprotective effect of VU0092273 and revealed activation of glia, indicating the involvement reactive astrogliosis in the mechanisms of neuroprotection. Our data suggest that selective activation/potentiation of mGlu5 signalling represents a promising strategy for the development of new interventions to reduce or prevent ischemia-induced neuronal death.
- |||||||||| sirolimus / Generic mfg.
Journal: Brain-penetrant PQR620 mTOR and PQR530 PI3K/mTOR inhibitor reduce huntingtin levels in cell models of HD. (Pubmed Central) - Jan 8, 2021 Induction of autophagy, for example by the inhibition of mechanistic target of rapamycin (mTOR) signaling, has been shown to reduce HTT levels and aggregates...As proof of principle, reduction of aggregates and levels of soluble mHTT were demonstrated upon treatment with both compounds. Originally developed for cancer treatment, these second generation mTORC1/2 and PI3K/mTOR inhibitors show brain penetrance and efficacy in cell models of HD, making them candidate molecules for further investigations in HD.
- |||||||||| Journal: MicroRNA-425-5p promotes breast cancer cell growth by inducing PI3K/AKT signaling. (Pubmed Central) - Jan 8, 2021
Moreover, miR-425-5p bound to the 3'UTR of PTEN mRNA, and downregulated the expression levels of PTEN in both mRNA and protein levels in breast cancer cells. Collectively, the results above demonstrated that miR-425-5p was involved in the tumorigenesis of breast cancer by inducing PI3K/AKT signaling and indicated that miR-425-5p could be as a potential target for breast cancer therapy in the future.
- |||||||||| bleomycin / Generic mfg.
Journal: CXCL16/CXCR6 axis promotes bleomycin-induced fibrotic process in MRC-5 cells via the PI3K/AKT/FOXO3a pathway. (Pubmed Central) - Jan 8, 2021 The results from this investigation may contribute to the development of protection against soft tissue changes induced by smokeless tobacco in the human oral cavity. CXCL16/CXCR6 axis promotes proliferation and collagen production of MRC-5 cells by the PI3K/AKT/FOXO3a signaling pathway, and inhibition of the CXCL16/CXCR6 axis may provide a new therapeutic strategy targeting pulmonary fibrosis.
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