- |||||||||| pictilisib (GDC-0941) / Roche, PI-103 / Roche
Modulation of YBX1 phosphorylation determines epidermal stem cell function (ePoster Stage 5; Poster Hall space (NS Building)) - Mar 4, 2023 - Abstract #ISID2023ISID_447; Furthermore, PI3K inhibitors increase the speed of epidermal wound closure in a wound healing model and epidermal regeneration model utilizing 3D skin equivalents. Our findings have uncovered a new level of posttranscriptional control of aging epidermal stem cell function by YBX1, which is required to maintain epidermal regenerative potential.
- |||||||||| Review, Journal: Development and safety of PI3K inhibitors in cancer. (Pubmed Central) - Mar 2, 2023
Here, the focus is on the development of PI3K inhibitors in cancer therapy, with particular emphasis on isoform-specific PI3K inhibitors. The most common adverse effects of PI3K inhibitors are also covered, as well as potential mechanisms and management approaches.
- |||||||||| LY294002 / Eli Lilly
Preclinical, Journal: Anti-inflammatory Effect of a Limonin Derivative In Vivo and Its Mechanisms in RAW264.7 Cells. (Pubmed Central) - Mar 2, 2023 The data indicated that I-C-1 likely acts as an inhibitor of PI3K, exerting anti-inflammatory effects by inhibiting the PI3K/AKT/NF-?B signaling pathway. Based on these findings, we believe that I-C-1 has the potential to be further developed as a potential therapeutic agent for inflammatory-related diseases.
- |||||||||| Aliqopa (copanlisib) / Bayer
Enrollment change, Trial completion date, Trial termination, Trial primary completion date: Safety, Tolerability, Efficacy and Pharmacokinetics of Copanlisib in Pediatric Patients (clinicaltrials.gov) - Mar 1, 2023 P1/2, N=31, Terminated, No abstract available N=142 --> 31 | Trial completion date: Apr 2027 --> Feb 2023 | Recruiting --> Terminated | Trial primary completion date: Feb 2025 --> Feb 2023; no anticipated benefit over available standard therapies
- |||||||||| Ukoniq (umbralisib) / TG Therap, Briumvi (ublituximab-xiiy) / TG Therap, Neuraxpharm, Calquence (acalabrutinib) / AstraZeneca
Enrollment closed, Enrollment change, Combination therapy: Acalabrutinib, Umbralisib, and Ublituximab for the Treatment of Previously Untreated Mantle Cell Lymphoma (clinicaltrials.gov) - Mar 1, 2023 P2, N=12, Active, not recruiting, N=142 --> 31 | Trial completion date: Apr 2027 --> Feb 2023 | Recruiting --> Terminated | Trial primary completion date: Feb 2025 --> Feb 2023; no anticipated benefit over available standard therapies Suspended --> Active, not recruiting | N=27 --> 12
- |||||||||| Journal: Turning down PI3K/AKT/mTOR signalling pathway by natural products: an in silico multi-target approach. (Pubmed Central) - Mar 1, 2023
Besides, MM-GBSA binding free energy calculations, MD simulations, and ADMET prediction were carried out, leading to 5 potential triple-target inhibitors namely, ZINC000014644152, ZINC000014760695, ZINC000014644839, ZINC000095099451, and ZINC000005998557. In conclusion, these inhibitors may be possible leads for inhibiting PI3K/AKT/mTOR pathway, and they may be further evaluated in vitro and clinically as anticancer agents.
- |||||||||| FDA Accelerated Approval: Oncology Nurse Implications with PI3K Inhibitors (Poster Monitor 15) - Feb 28, 2023 - Abstract #ONS2023ONS_368;
Timely completion of these studies is important for ensuring safe and effective therapies are available to patients. Oncology nurses, especially those directly involved in clinical trials, are well positioned to improve future drug development in this space and should be familiar with the current regulatory landscape.
- |||||||||| Zejula (niraparib) / GSK, J&J, Aliqopa (copanlisib) / Bayer
Trial completion date, Trial primary completion date: Niraparib and Copanlisib in Treating Patients With Recurrent Endometrial, Ovarian, Primary Peritoneal, or Fallopian Tube Cancer (clinicaltrials.gov) - Feb 28, 2023 P1, N=44, Recruiting, Oncology nurses, especially those directly involved in clinical trials, are well positioned to improve future drug development in this space and should be familiar with the current regulatory landscape. Trial completion date: Dec 2022 --> Dec 2023 | Trial primary completion date: Dec 2022 --> Dec 2023
- |||||||||| chloroquine phosphate / Generic mfg., temozolomide / Generic mfg.
Journal: Magnolol induces cytotoxic autophagy in glioma by inhibiting PI3K/AKT/mTOR signaling. (Pubmed Central) - Feb 27, 2023 Temozolomide is the only FDA-approved drug for its management...To confirm the cytotoxic effect of Magnolol-induced autophagy, we used Chloroquine, a late-stage autophagy inhibitor...Additionally, Magnolol showed no toxicity in non-cancerous cell lines as well as rat organs. Thus, we concluded that Magnolol is an excellent candidate for developing new therapeutic strategies for glioma management.
- |||||||||| Journal, Tumor cell: A Peptide-Conjugated Probe with Cleavage-Induced Morphological Change for Treatment on Tumor Cell Membrane. (Pubmed Central) - Feb 17, 2023
Thus, the promoted Ca influx by DP-induced cell membrane breakage and decreased Na /K -ATPase activity by LFA-assembled nanofibers wrapping the cells can inhibit PI3K-Akt signaling pathway, leading to the inhibition of tumor cell growth and metastasis. This peptide-conjugated probe undergoes in situ morphological transformation on the cell membrane, exhibiting great potential in tumor therapy.
- |||||||||| doxorubicin hydrochloride / Generic mfg.
Journal: Stomatin-like protein 2 deficiency exacerbates adverse cardiac remodeling. (Pubmed Central) - Feb 14, 2023 We developed doxorubicin (Dox), angiotensin (Ang) II, and myocardial ischemia-reperfusion (I/R) injury induced cardiac remodeling model and Dox treated H9C2 cell injury model using SLP-2 knockout (SLP-2) mice and H9C2 cells with low SLP-2 expression...In addition, the oxidative stress, apoptosis and autophagy levels of H9C2 cells with low SLP-2 expression were further enhanced, and the PI3K-Akt-mTOR signaling pathway was further inhibited under Dox stimulation. Our results suggest that SLP-2 deficiency promotes myocardial fibrosis, disrupts normal mitochondrial function, overactivates autophagy via PI3K-Akt-mTOR signaling pathway, affects the level of ubiquitination, leads to irreversible myocardial damage, and ultimately exacerbates adverse cardiac remodeling.
- |||||||||| LY294002 / Eli Lilly
Journal: SHP-2-induced M2 polarization of tumor associated macrophages via IL-4 regulate colorectal cancer progression. (Pubmed Central) - Feb 14, 2023 The relationship between SHP-2 and PI3K pathway was further verified by adding PI3K inhibitor LY294002...In terms of cellular behavior, wound healing and transwell data showed that low expression of SHP-2 enhanced the migration and invasion abilities of CRC cells. The low expression of SHP-2 induced by PHPS1 may regulate M2 polarization of TAMs and release of exosomes through PI3K/AKT pathway, thereby enhancing the migration and invasion ability of CRC cells.
- |||||||||| sirolimus / Generic mfg.
Review, Journal: Current State and Future Challenges for PI3K Inhibitors in Cancer Therapy. (Pubmed Central) - Feb 12, 2023 The phosphoinositide 3 kinase (PI3K)-protein kinase B (PKB/AKT)-mammalian target of the rapamycin (mTOR) axis is a key signal transduction system that links oncogenes and multiple receptor classes which are involved in many essential cellular functions...As the oncogenic activation of the PI3K/AKT/mTOR pathway often occurs alongside mutations in other signalling networks, combination therapy should be considered. In this review, we highlight recent advances in the knowledge of the PI3K pathway and discuss the current state and future challenges of targeting this pathway in clinical practice.
- |||||||||| Journal: PEDF Protects Endothelial Barrier Integrity during Acute Myocardial Infarction via 67LR. (Pubmed Central) - Feb 12, 2023
The activation of phosphorylation of PI3K-AKT-mTOR by PEDF was blocked after silencing 67LR, as were the protective effects of PEDF on ZO-1. Therefore, we have reason to believe that PEDF increased ZO-1 expression through the 67LR-dependent PI3K-AKT-mTOR signaling pathway, thus maintaining tight junction stability and protecting cardiac function.
- |||||||||| Journal: Metabolic stress-induced human beta-cell death is mediated by increased intracellular levels of adenosine. (Pubmed Central) - Feb 10, 2023
It is concluded that intracellular adenosine/2'-deoxyadenosine regulates negatively the PI3K pathway and is therefore an important mediator of beta-cell apoptosis. Adenosine levels are controlled, at least in part, by ADA1, and strategies to upregulate ADA1 activity, during conditions of metabolic stress, could be useful in attempts to preserve beta-cell mass in diabetes.
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