- |||||||||| Journal: Deep Sea Water Alleviates Tau Phosphorylation and Cognitive Impairment via PI3K/Akt/GSK-3β Pathway. (Pubmed Central) - Mar 25, 2022
Taken together, these data elucidated that DSW could improve Tau hyperphosphorylation and cognitive impairment, which were closely related with the stimulation of Akt/GSK-3β signaling, and the neuroprotective effects of DSW should be contributed to the synergistic effects of major and trace elements in it, such as Mg, V, Cr, Zn, and Se. These experimental evidence indicated that DSW may be explored as natural neuroprotective food for the prevention and treatment of AD.
- |||||||||| Xalkori (crizotinib) / Pfizer, Lynparza (olaparib) / Merck (MSD), AstraZeneca
Clinical, Journal, PARP Biomarker: MET inhibition enhances PARP inhibitor efficacy in castration-resistant prostate cancer by suppressing the ATM/ATR and PI3K/AKT pathways. (Pubmed Central) - Mar 24, 2022 Further analysis of the underlying molecular mechanism underlying the MET suppression-induced drug sensitivity revealed that olaparib and crizotinib could together downregulate the ATM/ATR signaling pathway, inducing apoptosis by inhibiting the phosphoinositide 3-kinase/protein kinase B (PI3K/AKT) pathway, enhancing the olaparib-induced antitumour effect in DU145 and PC3 cells. In conclusion, we demonstrated that MET inhibition enhances sensitivity of CRPC to PARP inhibitors by suppressing the ATM/ATR and PI3K/AKT pathways and provides a novel, targeted therapy regimen for CRPC.
- |||||||||| Preclinical, Journal: Antiandrogenic activity of Riboflavin 5'-phosphate (FMN) in 22Rv1 and LNCaP human prostate cancer cell lines. (Pubmed Central) - Mar 24, 2022
Our data suggest that the androgen receptor signaling is regulated through PI3K-Akt-MDM2 pathway in 22Rv1 cells. Together, our results indicate that FMN facilitated the degradation of androgen receptor in 22Rv1 cells and inhibited the expression of androgen regulated genes by competing the binding of DHT to androgen receptor in LNCaP cells, demonstrating its therapeutic potential as an antiandrogen.
- |||||||||| Iclusig (ponatinib) / Takeda, Otsuka, Incyte, lestaurtinib (CEP-701) / Teva, Kyowa Kirin
Journal: Ponatinib, Lestaurtinib and mTOR/PI3K inhibitors are promising repurposing candidates against Entamoeba histolytica. (Pubmed Central) - Mar 23, 2022 Two classes of compounds are most interesting for further investigations: the Bcr-Abl TK inhibitors, with the ponatinib (EC 0.39) as most potent and mTOR or PI3K inhibitors with 8 compounds in clinical development, of which 4 have nanomolar potency. Overall, these are promising candidates and represent a significant advance for drug development against E. histolytica.
- |||||||||| Venclexta (venetoclax) / Roche, AbbVie, Gazyva (obinutuzumab) / Roche, Biogen, Nippon Shinyaku, Rituxan (rituximab) / Biogen, Zenyaku Kogyo, Roche
Review, Journal, IO biomarker: Current Treatment of Chronic Lymphocytic Leukemia: The Diminishing Role of Chemoimmunotherapy. (Pubmed Central) - Mar 23, 2022 While novel-agent-based front-line approaches are appropriate for most patients, fludarabine, cyclophosphamide, and rituximab (FCR) remains a consideration for a selected population of young patients with immunoglobulin heavy chain variable region gene (IGHV)-mutated disease because of the possibility of a prolonged remission following FCR...Finally, we examine therapies with combinations of novel agents, and novel agents in development, including covalent and noncovalent BTK inhibitors, PI3K inhibitors, B-cell lymphoma 2 (BCL2) inhibitors, immunotherapies, and cellular therapies. With effective approved options and new agents in development, the role of chemoimmunotherapy in the management of CLL has diminished.
- |||||||||| LY294002 / Eli Lilly
Journal: Inhibition of PI3K/AKT/mTOR Signalling Pathway Activates Autophagy and Suppresses Peritoneal Fibrosis in the Process of Peritoneal Dialysis. (Pubmed Central) - Mar 23, 2022 In this experiment, a high-glucose (HG)-induced peritoneal fibrosis rat model was successfully established via intraperitoneal injection of HG peritoneal dialysate, and the phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002 and the mechanistic target of rapamycin (mTOR) inhibitor rapamycin were used to treat peritoneal fibrosis rats...The current data indicated that inhibition of PI3K/AKT/mTOR signalling pathway activated autophagy and suppressed PF in the process of PD. Therefore, intervention in this signalling pathway may become a research goal for the prevention and treatment of PF, which has important clinical significance.
- |||||||||| Review, Journal: New Advances in Targeted Therapy of HER2-Negative Breast Cancer. (Pubmed Central) - Mar 23, 2022
However, molecular targeted therapy is mainly aimed at HER2-positive breast cancer and has not yet achieved satisfactory curative effect on HER2-negative breast cancer. This article describes the potential targets that may be used for breast cancer treatment from the aspects of PI3K/AKT signaling pathway, DDR, angiogenesis, the cell cycle, breast cancer stem cells, etc., and explores possible inhibitors for the treatment of HER2-negative breast cancer, such as PI3K inhibitors, AKT inhibitors and m-TOR inhibitors that inhibit the PI3K/AKT signaling pathway, small molecule tyrosine kinase inhibitors that restrain angiogenesis, CDK inhibitors, aurora kinase inhibitors and HDAC inhibitors that block cell cycle, as well as the drugs targeting breast cancer stem cells which have been a hit, aiming to provide a new idea and strategy for the treatment of HER2-negative breast cancer.
- |||||||||| fasudil / Generic mfg.
Journal: Dual efficacy of Fasudil at improvement of survival and reinnervation of flap through RhoA/ROCK/PI3K/Akt pathway. (Pubmed Central) - Mar 23, 2022 As for reinnervation, Neurofilament-200 fluorescent staining revealed that at days 15 and 30 after flap harvest, only in the Fasudil group could new axons be observed. It can be concluded that Fasudil could simultaneously improve the survival and axon growth after flap harvest, a dual efficacy achieved by inhibition of the RhoA/ROCK pathway, which in turn activates /PI3K/AKT pathway.
- |||||||||| Zydelig (idelalisib) / Gilead
Journal: P300/CBP inhibition sensitizes mantle cell lymphoma to PI3Kδ inhibitor idelalisib. (Pubmed Central) - Mar 17, 2022 Therefore, additional inhibition of p300/CBP blocked MAPK/ERK signaling, which rendered maintaining activation to PI3K-mTOR downstream signals p-S6 and p-4E-BP1, thus leading to suppression of cell growth and tumor progression and eliminating the intrinsic resistance to idelalisib ultimately. Our results provide a promising combination therapy for MCL and highlight the potential use of epigenetic inhibitors targeting p300/CBP to reverse drug resistance in tumor.
- |||||||||| Journal: Epicatechin gallate prevents the de novo synthesis of fatty acid and the migration of prostate cancer cells. (Pubmed Central) - Mar 17, 2022
PI3K/AKT/mTOR signaling pathway, which exhibits regulatory effect on lipogenesis, is also inhibited under epicatechin gallate treatment, while pretreatment with AKT activator SC79 or mTOR activator MHY1485 blocks the inhibitory effect of epicatechin gallate on the expression of lipogenic genes and the migration of prostate cancer cells. In conclusion, this study revealed that epicatechin gallate impairs the synthesis of fatty acids via inhibition PI3K/AKT/mTOR signaling pathway and then attenuates the migration of prostate cancer cells.
- |||||||||| Review, Journal: Regulation of miR-30b in cancer development, apoptosis, and drug resistance. (Pubmed Central) - Mar 17, 2022
In addition, miR-30 plays a significant role in alleviating drug resistance in tumor cells. Although the use of miR-30b as a clinical diagnostic indicator or anticancer drug is still facing great difficulties in the short term, with the deepening of research, the potential application of miR-30b is emerging.
- |||||||||| LY294002 / Eli Lilly, PD98059 / Wayne State University
Journal, IO biomarker: Euphorbia angustifolia lactone B inhibits A549 proliferation and induces apoptosis. (Pubmed Central) - Mar 16, 2022 Moreover, 20 μ mol/L LY294002 (an PI3K inhibitor) + 120μg/mL JB and 10μmol/L PD98059 (an ERK inhibitor) +120μg/mL JB also increased apoptosis rates of A549 cells. JB could induced cell apoptosis through promoting endogenous mitochondrial signal transduction pathway and inhibiting PI3K/ERK pathway.
- |||||||||| Review, Journal: Thiram exposure in environment: A critical review on cytotoxicity. (Pubmed Central) - Mar 16, 2022
We have summarized several impacts of thiram on animals: the effects of the perspectives of oxidative stress, mitochondrial damage, autophagy, apoptosis, and the IHH/PTHrP pathway on regulating abnormal skeletal development in particular tibial dyschondroplasia and kyphosis; angiogenesis inhibition was investigated from the perspective of angiogenesis factor inhibition, PI3K/AKT signaling pathway and CD147; the inhibition effect of thiram on fibroblasts and erythrocytes via the perspective of oxidative stress, mitochondrial damage and inhibition of growth factors in animal skin fibroblasts and erythrocytes; studied fertilized egg size, reduced fertility, neurodegeneration, and immune damage from the perspectives of CYP51 inhibition and dopamine-b-hydroxylase inhibition in the reproductive system, vitamin D deficiency in the nervous system, and inflammatory damage in the immune system; embryonic dysplasia in terms of thyroid hormone repression in animal embryonic development and repression of the SOX9a transcription factor. The elucidation of the mechanisms of toxicity of thiram on various organs of animals at molecular level will enable a more detailed understanding of the mechanisms of toxicity of thiram in animals and will facilitate the exploration of the treatment of thiram poisoning at molecular level.
- |||||||||| LY294002 / Eli Lilly
Preclinical, Journal: Calcium-Prolactin Secretion Coupling in Rat Pituitary Lactotrophs Is Controlled by PI4-Kinase Alpha. (Pubmed Central) - Mar 15, 2022 Wortmannin, a PI3K and PI4K inhibitor, but not LY294002, a PI3K inhibitor, blocked spontaneous action potential driven PRL release with a half-time of ~20 min when applied in 10 µM concentration, leading to accumulation of intracellular PRL content...In contrast, PIK93, a specific inhibitor of PI4KB, and ISA2011B and UNC3230, specific inhibitors of PIP5K1A and PIP5K1C, respectively, did not affect PRL release. These experiments revealed a key role of PI4KA in calcium-secretion coupling in pituitary lactotrophs downstream of voltage-gated and PI(4, 5)P2-dependent calcium signaling.
|