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  • ||||||||||  Zyclara (imiquimod) / Mochida, Viatris, Bausch Health
    Journal:  Essential Oil of Matricaria chamomilla Alleviate Psoriatic-Like Skin Inflammation by Inhibiting PI3K/Akt/mTOR and p38MAPK Signaling Pathway. (Pubmed Central) -  Jan 15, 2024   
    At the same time, we prepared imiquimod-induced psoriatic-like skin inflammation in mice to investigate thoroughly the potential inhibition functions of MCEO on psoriatic skin injury and inflammation...MCEO ameliorated skin injury in IMQ-induced psoriatic-like skin inflammation of mice by downregulating the levels of inflammatory cytokines but not IL-17A. Thus, anti-inflammatory plant drugs with different targets with combined applications were a potential therapeutic strategy in psoriasis.
  • ||||||||||  Preclinical, Journal:  Exploration of anti?osteosarcoma activity of asiatic acid based on network pharmacology and in (Pubmed Central) -  Jan 12, 2024   
    In addition, asiatic acid decreased the levels of phosphorylated (p?)PI3K/PI3K and p?AKT/AKT, increased reactive oxygen species (ROS) and upregulated the levels of p?ERK1/2/ERK1/2, p?p38/p38 and p?JNK/JNK in osteosarcoma cells. These results demonstrated that asiatic acid inhibited osteosarcoma cells proliferation by inhibiting PI3K/AKT and activating ROS/MAPK signaling pathways, suggesting asiatic acid is a potential agent against osteosarcoma.
  • ||||||||||  imatinib / Generic mfg.
    Journal, PARP Biomarker, IO biomarker:  Imatinib inhibits oral squamous cell carcinoma by suppressing the PI3K/AKT/mTOR signaling pathway. (Pubmed Central) -  Jan 12, 2024   
    Furthermore, imatinib suppressed migration and colony formation while promoting OSCC cell apoptosis by enhancing p53, Bax, and PARP expression levels and reducing Bcl-2 expression. Imatinib also inhibited the PI3K/AKT/mTOR signaling pathway and induced OSCC cell apoptosis, demonstrating the potential of imatinib as a treatment for oral cancer.
  • ||||||||||  palazestrant (OP-1250) / Olema Pharma
    Phase classification, Enrollment change, Combination therapy, Metastases:  Phase 1b Combo w/ Ribociclib and Alpelisib (clinicaltrials.gov) -  Jan 11, 2024   
    P1,  N=90, Recruiting, 
    Furthermore, a combination of ATR and PI3K inhibition by treatment with elimusertib and copanlisib has in Phase classification: P1b --> P1 | N=60 --> 90
  • ||||||||||  Journal:  A combined opposite targeting of p110? PI3K and RhoA abrogates skin cancer. (Pubmed Central) -  Jan 10, 2024   
    Together, our findings highlight the importance of targeting cancer cells and macrophages for skin cancer therapy, emerge a reverse link between ATX and RhoA and illustrate the benefit of p110? PI3K inhibition as a combinatorial regimen for the treatment of skin cancers.
  • ||||||||||  LY294002 / Eli Lilly
    Preclinical, Journal:  Periplaneta americana extract promotes hard palate mucosal wound healing via the PI3K/AKT signaling pathway in male mice. (Pubmed Central) -  Jan 10, 2024   
    Taken together, RA exerted antidepressant activities by modulating the hippocampal glucocorticoid signaling and hippocampal neurogenesis, which related to the BDNF/TrkB/PI3K signaling axis regulating GR nuclear translocation, provide evidence for the application of RA as a candidate for depression. Periplaneta americana extract shows promising effects for the promotion of hard palate mucosal wound healing and may be a novel candidate for clinical translation.
  • ||||||||||  Review, Journal:  Development of small-molecule inhibitors that target PI3K?. (Pubmed Central) -  Jan 8, 2024   
    Achieving selectivity can be accomplished through three primary strategies, namely, binding to the induced lipophilic pocket, targeting the unique amino acid residue of PI3K?, or using atropisomerism to lock conformation. In this review, we focus on advances in the development of these ?-isoform-selective PI3K inhibitors, providing potential guidance for the further development of novel clinical candidates.
  • ||||||||||  Journal:  PI3K signaling promotes formation of lipid-laden foamy macrophages at the spinal cord injury site. (Pubmed Central) -  Jan 8, 2024   
    RNA sequencing and in vitro analysis of foamy macrophages revealed increased autophagy and decreased phagocytosis after PI3K inhibition as potential mechanisms for reduced lipid accumulation. Together, our data suggest that the formation of pro-inflammatory foamy macrophages after SCI is due to the activation of PI3K signaling, which increases phagocytosis and decreases autophagy.
  • ||||||||||  LY294002 / Eli Lilly
    Journal:  Angiotensin-(1-7) Improves Islet ?-cell Dedifferentiation by Activating PI3K/Akt/FoxO1 Pathway. (Pubmed Central) -  Jan 8, 2024   
    Together, our data suggest that the formation of pro-inflammatory foamy macrophages after SCI is due to the activation of PI3K signaling, which increases phagocytosis and decreases autophagy. Ang-(1-7) may prevent high glucose-induced pathological dedifferentiation of pancreatic ?-cell by activating the PI3K/Akt/FoxO1 signaling pathway.
  • ||||||||||  Journal:  Spermidine activates adipose tissue thermogenesis through autophagy and fibroblast growth factor 21. (Pubmed Central) -  Jan 7, 2024   
    Knockdown of Fgf21 or inhibition of PI3K/AKT and AMPK pathways in brown adipocytes abolished the thermogenesis-promoting effect of spermidine, suggesting that the effect of spermidine on adipose tissue thermogenesis might be regulated by FGF21 signaling via the PI3K/AKT and AMPK pathways. The present study provides new insight into the mechanism of spermidine on obesity and its metabolic complications, thereby laying a theoretical basis for the clinical application of spermidine.
  • ||||||||||  LY294002 / Eli Lilly
    Chemoprotective Mechanisms of Skullcapflavone in Aflatoxin-induced toxICIty in Thle-3 Hepatocytes (Room 06, C-2) -  Jan 6, 2024 - Abstract #APASL2024APASL_1536;    
    Remarkably, LYS294002, a specific inhibitor of PI3K, impaired SKI protective effect on THLE-3 suggesting the role of the pathway. This study is the first report describing the protective activities of SKI against AFB1-induced toxicity on human hepatocytes and may help contribute to the development of pharmaceutical leads targeting aflatoxin poisoning and carcinogenicity.
  • ||||||||||  Halaven (eribulin mesylate) / Eisai, Aliqopa (copanlisib) / Bayer
    Trial completion date, Trial primary completion date, Combination therapy, Metastases:  Testing the Addition of Copanlisib to Eribulin for the Treatment of Advanced-Stage Triple Negative Breast Cancer (clinicaltrials.gov) -  Jan 3, 2024   
    P1/2,  N=106, Active, not recruiting, 
    HSP90AA1, EGFR, STAT1, and JAK2 may be the most relevant potential therapeutic targets for THA in the treatment of UC. Trial completion date: Dec 2023 --> Dec 2024 | Trial primary completion date: Dec 2023 --> Dec 2024
  • ||||||||||  LY294002 / Eli Lilly
    Preclinical, Journal:  Rosmarinic Acid Inhibits Ultraviolet B-Mediated Oxidative Damage via the AKT/ERK-NRF2-GSH Pathway In Vitro and In Vivo. (Pubmed Central) -  Dec 27, 2023   
    Treatment with the phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002, the ERK inhibitor U0126, and small interfering RNA (siRNA) gene silencing suppressed RA-enhanced GCLC, GSS, and NRF2 expression, respectively...These results suggest that RA protects against UVB-induced oxidative damage by activating AKT and ERK signaling to regulate NRF2 signaling and enhance GSH biosynthesis. Thus, RA treatment may be a promising approach to protect the skin from UVB-induced oxidative damage.
  • ||||||||||  Journal:  FBXO3 stabilizes USP4 and Twist1 to promote PI3K-mediated breast cancer metastasis. (Pubmed Central) -  Dec 26, 2023   
    Clinically, elevated expression of p110?/FBXO3/USP4/Twist1 is associated with poor overall survival (OS) and recurrence-free survival (RFS) of breast cancer patients. Taken together, this study reveals that the FBXO3-USP4-Twist1 axis is pivotal in PI3K-mediated breast tumor metastasis and that FBXO3/USP4 may be potential therapeutic targets for breast cancer treatment.
  • ||||||||||  Journal:  Human cytomegalovirus attenuates AKT activity by destabilizing insulin receptor substrate proteins. (Pubmed Central) -  Dec 25, 2023   
    Despite its penchant for remodeling host cell signaling pathways, our results reveal that HCMV relies upon a cell-intrinsic negative regulatory feedback loop to inactivate AKT. Given that pharmacological inhibition of PI3K/AKT potently induces HCMV reactivation from latency, our findings also imply that the expression of UL38 activity must be tightly regulated within latently infected cells to avoid spontaneous reactivation.
  • ||||||||||  The Mosaic Mind - Somatic Brain Mosaicism in Neurodevelopmental Disorders and Epilepsy (MTCC - 718) -  Dec 23, 2023 - Abstract #ACMG2024ACMG_385;    
    In many cases epilepsy surgery may offer a cure or provide significant improvement in seizure control and developmental outcomes. Advances in both genetics and neuroimaging (such as 7T MRI,FDG-PET, SPECT, and functional MRI ) continue to provide us with a better understanding of these disorders and are leading to improvement in medical and surgical therapies.Learning Objectives Explain somatic brain mosaicism in autism, intellectual disability, and neuropsychiatric disorders Identify deep sequencing and CSF cfDNA to detect somatic mosaicism in malformations of cortical development (MCD) Demonstrate how to clinically assess for brain mosaicism to improve care for children with intractable focal epilepsy Identify the role of neuroimaging in diagnosis and treatment in FCD and MCD Describe how genetic testing from SEEG brain samples could improve diagnosis and treatment of disease