PI3K inhib 
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  • ||||||||||  vistusertib (AZD2014) / AstraZeneca, AZD8186 / AstraZeneca
    Journal:  mTOR inhibition amplifies the anti-lymphoma effect of PI3Kβ/δ blockage in diffuse large B-cell lymphoma. (Pubmed Central) -  Nov 16, 2022   
    Collectively, our study reveals that subsets of DLBCLs are addicted to PI3Kβ/δ signaling and thus identifies a previously unappreciated role of the PI3Kβ isoform in DLBCL survival. Furthermore, our data demonstrate that combined targeting of PI3Kβ/δ and mTOR is effective in all major DLBCL subtypes supporting the evaluation of this strategy in a clinical trial setting.
  • ||||||||||  Journal:  The MASTL/PP2A cell cycle kinase-phosphatase module restrains PI3K-Akt activity in an mTORC1-dependent manner. (Pubmed Central) -  Nov 16, 2022   
    MASTL is directly phosphorylated by mTORC1, thereby limiting the PP2A/B55-dependent dephosphorylation of IRS1 and GRB10 downstream of mTORC1. Downregulation of MASTL results in increased glucose uptake in vitro and increased glucose tolerance in adult mice, suggesting the relevance of the MASTL-PP2A/B55 kinase-phosphatase module in controlling AKT and maintaining metabolic homeostasis.
  • ||||||||||  TGX-221 / Wuhan University, Pfizer
    Journal:  Platelet p110β mediates platelet-leukocyte interaction and curtails bacterial dissemination in pneumococcal pneumonia. (Pubmed Central) -  Nov 16, 2022   
    Using a mouse model of Streptococcus pneumoniae-induced pneumonia, we find that both platelet-specific p110β deficiency and pharmacologic inhibition of p110β with TGX-221 exacerbate disease pathogenesis by preventing platelet-monocyte and neutrophil interactions, diminishing their infiltration and enhancing bacterial dissemination...Our results demonstrate that platelet p110β dysfunction exacerbates pulmonary infection by impeding leukocyte functions. Thereby, our findings provide important insights into the immunomodulatory potential of PI3K inhibitors in bacterial infection.
  • ||||||||||  Journal:  Galangin inhibits neointima formation induced by vascular injury via regulating the PI3K/AKT/mTOR pathway. (Pubmed Central) -  Nov 15, 2022   
    In terms of mechanisms, galangin inhibited the PI3K/AKT/mTOR pathway, thereby suppressing VSMC's switch from a contractile to a synthetic phenotype, inhibiting VSMC proliferation, migration and phenotypic switching and upregulating the Beclin1 protein expression levels and the ratio of LC3BII/I, promoting VSMC autophagy, and thereby inhibiting neointimal hyperplasia after vascular injury. Our study suggests that galangin inhibits neointimal hyperplasia after vascular injury by inhibiting smooth muscle cell proliferation, migration and phenotypic switching and by promoting autophagy, and that galangin may be a promising drug for the prevention and treatment of vascular restenosis after PCI.
  • ||||||||||  Review, Journal:  Targeting PI3K/Akt signaling in prostate cancer therapy. (Pubmed Central) -  Nov 15, 2022   
    Anti-tumor compounds suppress PI3K/Akt signaling in impairing prostate tumor progression. Furthermore, upstream regulators such as miRNAs, lncRNAs and circRNAs regulate PI3K/Akt signaling and it has clinical implications for prostate cancer patients.
  • ||||||||||  omipalisib (GSK2126458) / GSK
    Journal:  LncRNA RHPN1-AS1 inhibition induces autophagy and apoptosis in prostate cancer cells via the miR-7-5p/EGFR/PI3K/AKT/mTOR signaling pathway. (Pubmed Central) -  Nov 15, 2022   
    Furthermore, overexpression of RHPN1-AS1 promoted phosphorylation of phosphatidylinositol 3-kinase (PI3K), AKT and mTOR, inhibited LC3-I to LC3-II conversion and reduced apoptosis in PCa cells, while GSK2126458 (an inhibitor of PI3K) reversed the effect of RHPN1-AS1 on PCa cells. In summary, RHPN1-AS1 acted as a ceRNA of miR-7-5p to upregulate EGFR expression, silencing RHPN1-AS1 suppressed PCa tumor progression by inducing autophagy and apoptosis in PCa cells through the miR-7-5p/EGFR/PI3K/AKT/mTOR pathway.
  • ||||||||||  Journal, IO biomarker:  Immunotherapy combinations for chronic lymphocytic leukemia: Advantages and disadvantages. (Pubmed Central) -  Nov 15, 2022   
    Rituximab and obinutuzumab have been combined with chemotherapy, and more recently, with BTK inhibitors, PI3K inhibitors and venetoclax...Venetoclax is typically combined with anti-CD20 Mabs in CLL. Generally, the optimal sequencing of therapies remains to be established, and the selection of upfront therapy needs to be tailored to the individual patient.
  • ||||||||||  LY294002 / Eli Lilly, PF-573228 / Pfizer
    Journal:  Periodontal Ligaments Enhance Neurite Outgrowth in Trigeminal Ganglion Neurons through Wnt5a Production Induced by Mechanical Stimulation. (Pubmed Central) -  Nov 15, 2022   
    Similarly, PF573228, a focal adhesion kinase inhibitor, attenuated Akt- and ERK1/2-phosphorylation and Wnt5a expression...These findings reveal the indirect mechanisms that Wnt5a, released from the connective tissues in response to mechanical stimulation, enhances the outgrowth of the peripheral nerves. Our study suggests that the peripheral connective tissues regulate peripheral nerve homeostasis and that Wnt5a signaling could be targeted for the treatment of peripheral nerve disorders.
  • ||||||||||  bortezomib / Generic mfg.
    Journal:  Effects of cancer-associated point mutations on the structure, function, and stability of isocitrate dehydrogenase 2. (Pubmed Central) -  Nov 14, 2022   
    Using overlapping PCR, transfection, immunoblotting, immunoprecipitation, measurements of enzyme activity, glucose, lactic acid, ATP, and reactive oxygen species (ROS), cell viability, protein degradation assays post-inhibition of the 26S proteasome (bortezomib) or HSP90 (17-AAG), and a homology model, we demonstrated that the properties of ten cancer-associated IDH2 variants (R140G/Q/W and R172S/K/M/W/G/C/P) arising from point mutations are closely related to their structure and stability...The homology model further revealed that changes in conformation and IDH2 protein stability appeared to be associated with these point mutations. Taken together, our findings provide information important for understanding the molecular mechanisms of IDH2 mutations in tumors.
  • ||||||||||  LY294002 / Eli Lilly, SB202190 / Amgen, PD98059 / Wayne State University
    Journal:  Seeking an Important Role on Metabolomics-Effects of β-Estradiol on Lipoprotein Metabolism in Mammary Tumors (Pubmed Central) -  Nov 12, 2022   
    In addition, the effect of E on active LPL secretion was markedly suppressed by an inhibitor of mammalian target of rapamycin complex (mTORC) 1 and 2, KU0063794, but not by the mTORC1 inhibitor, rapamycin. Furthermore, a small interfering RNA (siRNA)-mediated decrease in the expression of rapamycin-insensitive companion of mTOR (Rictor), a pivotal component of mTORC2, suppressed the secretion of LPL by E. Stimulatory secretion of LPL by E from the tumor cells is closely associated with activation of mTORC2 rather than mTORC1, possibly via the MAPK cascade.
  • ||||||||||  vancomycin / Generic mfg.
    Preclinical, Journal:  P2X4 receptor stimulation enhances MrgprB2-mediated mast cell activation and pseudoallergic reactions in mice. (Pubmed Central) -  Nov 12, 2022   
    ATP alone induced minimal PMC degranulation but markedly enhanced degranulation induced by the MrgprB2 agonist compound 48/80 (CP48/80), substance P, PAMP-12, and vancomycin...In MC-deficient Kit mice, reconstitution with MCs obtained from wild-type mice led to a more severe anaphylactic response to CP48/80 compared to that from P2X4R-deficient mice. P2X4R-mediated effect may be involved in MrgprB2-mediated MC activation in vivo and is a potential target for alleviating pseudoallergic reactions.
  • ||||||||||  Piqray (alpelisib) / Novartis
    Journal:  Alpelisib for the treatment of PIK3CA-related head and neck lymphatic malformations and overgrowth. (Pubmed Central) -  Nov 9, 2022   
    Guaianolide 8 was the most potent sesquiterpene lactone, inhibiting the PI3K/AKT pathway with an IC value of 8.9 ± 0.9 μM. Individuals with head and neck PROS treated with alpelisib had decreased malformation size and locoregional overgrowth, improved function and symptoms, and fewer invasive procedures.
  • ||||||||||  hydroquinone / Generic mfg.
    Preclinical, Journal:  Tert-butylhydroquinone protects the retina from oxidative stress in STZ-induced diabetic rats via the PI3K/Akt/eNOS pathway. (Pubmed Central) -  Nov 9, 2022   
    This study aims to investigate whether tert-butylhydroquinone protects the retina from oxidative stress in STZ-induced experimental diabetic rats through the activation of phosphinositide 3-kinase (PI3K)/Akt/endothelial nitric oxide synthase (eNOS) pathway.In vitro, NO, reactive oxygen species(ROS), eNOS, p-eNOS Ser1179, Akt, p-Akt Ser473 and L-NAME protein expression was analyzed within rMC-1 cells cultivated within normal control(NC), high glucose (HG) and HG-containing tert-butyl hydroquinone (tBHQ) (5 μM) medium...tBHQ alleviates oxidative stress during diabetic retinopathy by upregulating the PI3K/Akt/eNOS pathway and partially restoring the structure and function of the retina. It may play a role in delaying vision loss caused by diabetic retinopathy.
  • ||||||||||  Inlyta (axitinib) / Pfizer
    Journal:  Novel therapeutic approaches for salivary gland carcinomas (Pubmed Central) -  Nov 8, 2022   
    Moreover, cross-entity therapeutics such as antiandrogenic therapy, HER2 inhibition, and PI3K inhibition are also coming to the fore. For metastatic/recurrent salivary gland carcinomas that cannot be treated with targeted therapy, platinum-based chemotherapies continue to be therapy of choice.
  • ||||||||||  Piqray (alpelisib) / Novartis
    Preclinical, Journal:  Short-term PI3K inhibition prevents breast cancer in preclinical models. (Pubmed Central) -  Nov 8, 2022   
    Furthermore, we showed that alpelisib suppressed ex vivo expansion of patient-derived atypical hyperplasia. Together, these data indicate that the progression of precancerous breast lesions heavily depends on the PI3K signaling, and that prophylactic targeting of PI3K activity can prevent breast cancer.
  • ||||||||||  LY294002 / Eli Lilly
    Preclinical, Journal:  Gracillin exerts anti-melanoma effects in vitro and in vivo: role of DNA damage, apoptosis and autophagy. (Pubmed Central) -  Nov 6, 2022   
    Induction of DNA damage, inhibition of PI3K/AKT/mTOR signaling and suppression of STAT3 signaling are involved in gracillin-mediated cell cycle arrest, autophagic cell death and apoptosis, respectively, in melanoma cells. These findings provide novel insights into the anti-melanoma molecular mechanisms of gracillin, and suggest a potential role of gracillin in melanoma management.
  • ||||||||||  LY294002 / Eli Lilly
    Journal:  NGF regulates sertoli cell growth and prevents LPS-induced junction protein damage via PI3K/AKT/NFκB signaling. (Pubmed Central) -  Nov 5, 2022   
    We further demonstrated that NGF prevented the inflammatory response of Sertoli cells via the PI3K/AKT/NFκB signaling pathway, similar to the effect of the PI3K-inhibitor, LY294002, which is modified by the PI3K activator, 740Y-P. These results provide insights for devising strategies for protecting the male reproductive system and curing or preventing associated pathological conditions.
  • ||||||||||  Nplate (romiplostim) / Amgen, Kyowa Kirin, Promacta (eltrombopag) / Novartis
    Low-Dose Rhein Sensitizes Platelet Production to Thrombopoietin Receptor Agonists (TPO-RA) in Immune Thrombocytopenia (ENMCC - Hall D) -  Nov 4, 2022 - Abstract #ASH2022ASH_5553;    
    Diacerein, hydrolyzed into its active metabolite rhein after oral administration, is a non-steroidal anti-inflammatory drug used in osteoarthritis...Flow cytometry analysis suggested that the combination therapy significantly increased megakaryocyte percentage and polyploidization than romiplostim in ITP mice... In sum, our data reveal a sensitizing role of rhein to TPO-RA in megakaryocyte polyploidization and platelet formation in ITP, and this novel combination therapy warrants further investigation as an optimized strategy for ITP patients.