- |||||||||| quercetin (LY294002) / Eli Lilly
Journal: Prostate transmembrane protein androgen induced 1 is induced by activation of osteoclasts and regulates bone resorption. (Pubmed Central) - May 13, 2020 Inhibitors of bone resorption, such as alendronate, bafilomycin A1, and the PI3K inhibitor LY294002, suppressed the expression of Pmepa1 in osteoclasts...In addition, in sites of bone destruction observed in rats with adjuvant-induced arthritis, a marked high level of Pmepa1 expression was associated with the osteoclasts' resorbing bone. Our results suggest that Pmepa1 is a critical regulator of bone resorption and is a promising marker for activated osteoclasts and a potential therapeutic target in pathologic bone destruction.-Xu, X., Hirata, H., Shiraki, M., Kamohara, A., Nishioka, K., Miyamoto, H., Kukita, T., Kukita, A. Prostate transmembrane protein androgen induced 1 is induced by activation of osteoclasts and regulates bone resorption.
- |||||||||| Journal: Overexpression of ERBB4 rejuvenates aged mesenchymal stem cell and enhances angiogenesis via PI3K/AKT and MAPK/ERK pathway. (Pubmed Central) - May 13, 2020
ER4-aged-MSC secreted higher levels of angiopoietin, epithelial neutrophil activating peptide 78, VEGF, and fibroblast growth factor 2, and enhanced tube formation in HUVEC. The impact of ERBB4 on protein expression, proangiogenesis, cell behavior, and cytokine secretion was abolished by inhibiting PI3K/AKT and MAPK/ERK signaling pathway.-Liang, X., Ding, Y., Lin, F., Zhang, Y., Zhou, X., Meng, Q., Lu, X., Jiang, G., Zhu, H., Chen, Y., Lian, Q., Fan, H., Liu, Z. Overexpression of ERBB4 rejuvenates aged mesenchymal stem cell and enhances angiogenesis via PI3K/AKT and MAPK/ERK pathway.
- |||||||||| quercetin (LY294002) / Eli Lilly
Journal: Connexin43 enhances Wnt and PGE2-dependent activation of β-catenin in osteoblasts. (Pubmed Central) - May 13, 2020 Finally, we show that the activation of β-catenin by PGE2 required signaling through the phosphatidylinositol 3-kinase (PI3K)/Akt/glycogen synthase kinase 3 beta (GSK3β) pathway, as the PI3K inhibitor, LY-294002, disrupted the synergy between connexin43 and PGE2. These data show that connexin43 regulates Akt and β-catenin activity and synergistically enhances both Wnt-dependent and Wnt-independent β-catenin signaling in osteoblasts.
- |||||||||| clopidogrel / Generic mfg.
Preclinical, Journal: Chrysin ameliorates cerebral ischemia/reperfusion (I/R) injury in rats by regulating the PI3K/Akt/mTOR pathway. (Pubmed Central) - May 13, 2020 In vivo experiments, the rats were orally administrated with clopidogrel or chrysin once daily for 7 days before the experimental of ischemia and the rats were divided into 5 groups: the sham group, the I/R group, I/R + clopidogrel group, I/R + chrysin (10 mg/kg), I/R + chrysin (20 mg/kg) group...Chrysin markedly decreased the levels of TNF-α, IL-6 and IL-1β in supernatant of OGD/R-induced SH-SY5Y cells via activating PI3K/Akt/mTOR pathway. In conclusion, our study demonstrated that chrysin might be a potential therapeutic agent for cerebral ischemia.
- |||||||||| Journal: PI3Kβ links integrin activation and PI(3,4)P production during invadopodial maturation. (Pubmed Central) - May 13, 2020
Thus, integrin activation of PI3Kβ is coupled to the SHIP2-dependent production of PI(3,4)P which regulates the recruitment of PH domain-containing scaffolds such as lamellipodin to invadopodia. These findings provide novel mechanistic insight into the role of PI3Kβ in the regulation of invadopodia in breast cancer cells.
- |||||||||| volagidemab (REMD-477) / Amgen, REMD Bio
Trial completion date: Glucagon Receptor Inhibition to Enable Breast Cancer Patients to Benefit From PI3K Inhibitor Therapy (REMD-477) (clinicaltrials.gov) - May 10, 2020 P1, N=9, Not yet recruiting, Evidence from the 3D skin model demonstrates that the protection of SKPs against UV-mediated damage is primarily via the PI3K/Akt-mediated activation of the Nrf2/HO-1 pathway, indicating that SKPs may be a promising candidate for the treatment of photodermatoses. Trial completion date: Feb 2024 --> Jul 2023
- |||||||||| bb21217 / bluebird bio, BMS
Correlative Analysis from CRB-402: An Ongoing Phase 1 Clinical Study of bb21217 Anti-BCMA CAR T Cell Therapy () - May 9, 2020 - Abstract #ASGCT2020ASGCT_99; P1 Immunophenotyping data from ex vivo clinical samples, including memory phenotypes, and their relationship to DP phenotype and clinical outcome, will also be presented. These early data suggest that bb21217 DP enriched for early memory phenotypes is associated with more robust peak expansion and more durable disease control than bb21217 DP enriched for effector Phenotypes.
- |||||||||| Zydelig (idelalisib) / Gilead, Aliqopa (copanlisib) / Bayer
Clinical, Journal: Class 1 PI3K Clinical Candidates and Recent Inhibitor Design Strategies: A Medicinal Chemistry Perspective. (Pubmed Central) - May 9, 2020 The search for novel PI3K inhibitors has been at the forefront of academic and industrial medicinal chemistry with over 600 medicinal chemistry-based publications and patents appearing to date, leading to 38 clinical candidates and the launch of two drugs, idelalisib in 2014 and copanlisib in 2017. This Perspective will discuss medicinal chemistry design approaches to novel isoform-selective inhibitors through consideration of brief case histories of compounds that have progressed into clinical development or that have revealed new structural motifs in this highly competitive area of research.
- |||||||||| Review, Journal: The PI3K-AKT network at the interface of oncogenic signalling and cancer metabolism. (Pubmed Central) - May 9, 2020
Aberrant activation of this signalling network is one of the most frequent events in human cancer and serves to disconnect the control of cell growth, survival and metabolism from exogenous growth stimuli. Here we discuss our current understanding of the molecular events controlling cellular metabolism downstream of PI3K and AKT and of how these events couple two major hallmarks of cancer: growth factor independence through oncogenic signalling and metabolic reprogramming to support cell survival and proliferation.
- |||||||||| sirolimus / Generic mfg.
Journal: Mir-215-5p induces autophagy by targeting PI3K and activating ROS-mediated MAPK pathways in cardiomyocytes of chicken. (Pubmed Central) - May 7, 2020 Our results showed that overexpression of miR-215-5p could trigger myocardial autophagy through PI3K-threonine-protein kinase (AKT)-target of rapamycin (TOR) pathway...On the contrary, miR-215-5p inhibitor can enhance cell survival capacity against autophagy by inhibiting ROS-mitogen-activated protein kinase (MAPK) pathways and activating the PI3K/AKT/TOR pathway in cardiomyocytes. Together, our findings support that miR-215-5p may modulate cell survival programs by regulating autophagy, and miR-215-5p acts as an autophagic regulator in the regulatory feedback loop that regulates cardiomyocyte survival by modulating the PI3K/AKT/TOR pathway and ROS-dependent MAPK pathways.
- |||||||||| Review, Journal: PIK3CA in cancer: the past 30 years. (Pubmed Central) - May 7, 2020
Efforts to target PI3K were on the rise from that moment on, accompanied by the first clinical trials for PI3K inhibitor therapies. In the fourth decade of research, PI3K-based cancer drugs will continue to emerge, as will new knowledge regarding other uncovered functions of this protein and pathway.
- |||||||||| Journal: PIP4K2A as a negative regulator of PI3K in PTEN-deficient glioblastoma. (Pubmed Central) - May 7, 2020
Overexpression of PIP4K2A suppressed cellular and clonogenic growth in vitro and impeded tumor growth in vivo. Our results unravel a novel tumor-suppressive role of PIP4K2A for the first time and support the feasibility of combining oncogenomics with in vivo RNAi screen.
- |||||||||| Review, Journal: Phosphoinositide Phosphatases in Cancer Cell Dynamics-Beyond PI3K and PTEN. (Pubmed Central) - May 7, 2020
Recent studies have argued the role of phosphoinositides in cancer cell dynamics, including actin cytoskeletal rearrangement at the plasma membrane and the organization of intracellular compartments. The focus of this review is to summarize the impact of the activities of phosphoinositide phosphatases on intracellular signaling related to cancer cell dynamics and to discuss how the abnormalities in the activities of the enzymes alter the levels of phosphoinositides in cancer cells.
- |||||||||| Review, Journal: Receptor tyrosine kinases in PI3K signaling: the therapeutic targets in cancer. (Pubmed Central) - May 7, 2020
Blockage of PI3K pathway by targeted therapy on RTKs with tyrosine kinases inhibitors (TKIs) and monoclonal antibodies (mAbs) has achieved great progress in past decades; however, there still remain big challenges during their clinical application. In this review, we provide an overview about the most frequently encountered alterations in RTKs and focus on current therapeutic agents developed to counteract their aberrant functions, accompanied with discussions of two major challenges to the RTKs-targeted therapy in cancer - resistance and toxicity.
- |||||||||| Journal: Active PI3K abrogates central tolerance in high-avidity autoreactive B cells. (Pubmed Central) - May 7, 2020
Upon stimulation with T cell help factors, these B cells secrete antibodies in vitro but remain unable to secrete autoantibodies in vivo. Overall, our data demonstrate that activation of the PI3K pathway leads high-avidity autoreactive B cells to breach central, but not late, stages of peripheral tolerance.
- |||||||||| Review, Journal: Emerging role of PI3K/AKT in tumor-related epigenetic regulation. (Pubmed Central) - May 7, 2020
Increasing evidence has demonstrated that critical epigenetic modifiers are directly or indirectly modulated by PI3K/AKT signaling, and participate in oncogenicity of PI3K cascade in cancers. In this review, we revisit the mechanism of the PI3K/AKT signaling pathway modulating epigenetic reprogramming in cancer and attempt to establish the connection between PI3K/AKT cascade and the epigenome.
- |||||||||| Review, Journal: Role of the PI3K/AKT/mTOR signaling pathway in ovarian cancer: Biological and therapeutic significance. (Pubmed Central) - May 7, 2020
Despite the availability of strong pre-clinical and clinical data of PI3K/AKT/mTOR pathway inhibitors in OC, there is no FDA approved inhibitor available for the treatment of OC. Here, we outline the importance of PI3K/AKT/mTOR signaling pathway in OC tumorigenesis, proliferation and progression, and pre-clinical and clinical experience with several PI3K/AKT/mTOR pathway inhibitors in OC.
- |||||||||| AUM302 / AUM Biosci, doxorubicin hydrochloride / Generic mfg.
Journal: Anti-tumor effects of PIM/PI3K/mTOR triple kinase inhibitor IBL-302 in neuroblastoma. (Pubmed Central) - May 7, 2020 While IBL-302 treatment alone reduced tumor growth in vivo, combination therapy with low-dose cisplatin inhibited neuroblastoma PDX growth. Complementing conventional chemotherapy treatment with PIM/PI3K/mTOR inhibition has the potential to improve clinical outcomes and reduce severe late effects in children with high-risk neuroblastoma.
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