PI3K inhib 
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  • ||||||||||  Synribo (omacetaxine mepesuccinate) / Teva, Zalypsis (PM00104) / PharmaMar
    Review, Journal:  Translating molecular insights into clinical success: alkaloid-based therapies for leukemia. (Pubmed Central) -  Oct 30, 2024   
    This review discusses several potent alkaloids, such as homoharringtonine, chaetominine, matrine, and jerantinine B, which induce apoptosis, cell cycle arrest, and autophagy and inhibit signaling pathways including PI3K/Akt/mTOR, MAPK, and NF-?B...In addition, targeting leukemia stem cells (LSCs) with alkaloids such as zalypsis offers promise due to its ability to induce apoptosis without significantly affecting normal hematopoietic stem cells...For example, jerantinine B targets AML cells, while vincristine has shown success in lymphocytic leukemia...However, adverse effects such as neutropenia and hepatotoxicity necessitate careful management. Collectively, these findings emphasize the need for further research into alkaloid-based combination therapies to enhance efficacy and minimize toxicity, providing a promising avenue for innovative leukemia treatments.
  • ||||||||||  OP-11 / Ohara Pharma
    Journal:  ZSTK474 targeting PIK3R3 inhibits the Wilms' tumor through G0 / G1 phase arrest. (Pubmed Central) -  Oct 28, 2024   
    These findings suggest that l-securinine holds promise as a potential lead for future drug development in the fight against pancreatic adenocarcinoma. This research provides insight into the potential of ZSTK474 and other PI3K inhibitors for treating nephroblastoma.
  • ||||||||||  LY294002 / Eli Lilly
    Preclinical, Journal:  Shisandra Decoction Alleviates Parkinson's Disease Symptoms in a Mouse Model Through PI3K/AKT/mTOR Signalling Pathway. (Pubmed Central) -  Oct 28, 2024   
    PD mice were further divided into four groups of ten mice each: MPTP group, LY294002 group, Sch D group, and LY2940002 + Sch D group...The neuroprotective effect of Sch D may involve the suppression of abnormal autophagy and its antioxidant properties, which indirectly reduces ?-syn accumulation. Future studies should assess the impact of Sch D on oxidative stress markers to evaluate its antioxidant effects.
  • ||||||||||  eganelisib (IPI-549) / Infinity Pharma
    Journal:  STING agonists and PI3K? inhibitor co-loaded ferric ion-punicalagin networks for comprehensive cancer therapy. (Pubmed Central) -  Oct 26, 2024   
    The therapeutic effect of various nanohybrids were validated in the mice with spontaneous tumor in the colorectal area and tumor-bearing mice, which lead to the increase of ferroptosis, the activation of STING signaling pathway, and the repolarization of macrophages. Collectively, the cGAMP and IPI-549 co-loaded nanohybrids effectively reshaped the tumor immune microenvironment, and exhibited prominent treatment effect of anti-colorectal cancer in vitro, patient-derived organoids, and in vivo.
  • ||||||||||  chloroquine phosphate / Generic mfg.
    Journal:  Benzo(a)pyrene promotes autophagy to impair endometrial decidualization via inhibiting CXCL12/CXCR4 axis. (Pubmed Central) -  Oct 26, 2024   
    Using autophagy inhibitors 3-methyladenine and chloroquine in combination with BaP to treat DSCs, successfully weakened BaP-induced autophagy, and relieved decidual injury...In summary, this study demonstrates that BaP induces autophagy in DSCs by inhibiting the CXCL12/CXCR4 axis, leading to damage in endometrial decidualization during early pregnancy. The findings provide a critical chemokine-mediated regulatory mechanism involved in embryo implantation and contribute valuable knowledge to the reproductive toxicology of BaP.
  • ||||||||||  Preclinical, Journal:  Humanized patient-derived xenograft mouse model bearing ovarian clear cell carcinoma. (Pubmed Central) -  Oct 25, 2024   
    The findings provide a critical chemokine-mediated regulatory mechanism involved in embryo implantation and contribute valuable knowledge to the reproductive toxicology of BaP. This pioneering study successfully develop a humanized PDX model for OCCC, highlighting differential responses to treatments compared to conventional PDX models.
  • ||||||||||  Journal:  Denervation?induced NRG3 aggravates muscle heterotopic ossification via the ErbB4/PI3K/Akt signaling pathway. (Pubmed Central) -  Oct 25, 2024   
    In vivo, inhibition of the PI3K/Akt pathway effectively protected against muscle HO induced by peripheral nerve injury in mice. The present study demonstrated that the regulatory roles of NRG3 and the PI3K/Akt pathway in peripheral nerve injury exacerbated muscle HO and highlights a potential therapeutic intervention for treatment of peripheral nerve injury?induced muscle HO.
  • ||||||||||  Keytruda (pembrolizumab) / Merck (MSD), Erbitux (cetuximab) / Eli Lilly, Opdivo (nivolumab) / BMS
    Journal, PD(L)-1 Biomarker, IO biomarker:  Future investigative directions for novel therapeutic targets in head and neck cancer. (Pubmed Central) -  Oct 23, 2024   
    Identification of predictive biomarkers may guide the use of targeted agents and combination therapies. Clinical trials supported by strong preclinical data in relevant models are more likely to advance treatment options.
  • ||||||||||  Aspergillus-induced Activation of NLRP3 Inflammasome Can be Regulated by PI3K-? (PEARL; 3F) -  Oct 21, 2024 - Abstract #KATRDIC2024KATRDIC_235;    
    may have potential for treating fungi-induced severe allergic lung inflammation. Moreover, in a specific molecular phenotype of severe asthma, targeting the NLRP3 inflammasome may be a potential treatment avenue to address COVID-19.
  • ||||||||||  carboplatin / Generic mfg., cisplatin / Generic mfg.
    Review, Journal:  Potential antitumor activity of triptolide and its derivatives: Focused on gynecological and breast cancers. (Pubmed Central) -  Oct 21, 2024   
    In addition, TPL and its derivatives exert synergistic antitumor effects against gynecological and breast cancers when combined with existing antitumor drugs, such as carboplatin, cisplatin, and PI3K inhibitors. Moreover, we highlight the clinical potential of TPL analogs against cancer from bench to bedside and their prospects for future applications in gynecologic and breast cancers.
  • ||||||||||  Tirazone (tirapazamine) / Teclison, SRI International
    Journal:  Studies related to the enhanced the effect of 5-aminolevulinic acid-based photodynamic therapy combined with tirapazamine. (Pubmed Central) -  Oct 19, 2024   
    Moreover, we highlight the clinical potential of TPL analogs against cancer from bench to bedside and their prospects for future applications in gynecologic and breast cancers. 5-ALA-PDT combined with TPZ can inhibit cell proliferation, increase apoptosis, and inhibit the PI3K/Akt/mTOR pathway, thus inhibiting tumor growth and metastasis and improving anti-cancer effects.
  • ||||||||||  Piqray (alpelisib) / Novartis
    Journal:  Quantum biochemistry description of PI3K? enzyme bound to selective inhibitors. (Pubmed Central) -  Oct 17, 2024   
    In this work, molecular dynamics and quantum calculations were performed to investigate the molecular features guiding the binding of selective inhibitors, alpelisib and GDC-0326, into the ATP-binding pocket of PI3K?...In addition, residues Trp780, Ile800, Tyr836, Ile848, Gln859 Val850, Val851, Ile932 and Met922 are common hotspots for both inhibitors. Overall, the results from this work contribute to improving the understanding of the molecular mechanisms controlling selectivity and highlight important interactions to be considered during the rational design of new agents.Communicated by Ramaswamy H. Sarma.
  • ||||||||||  Piqray (alpelisib) / Novartis, Mekinist (trametinib) / Novartis, BeiGene, buparlisib (AN2025) / Adlai Nortye
    The combination of PI3Ki (phosphatidylinositol-3-kinase inhibitor) and MEKi (mitogen-activated protein kinase inhibitor) as a promising treatment option for melanoma patients with NRAS-mutated tumors. (ePoster Self-Study 3) -  Oct 17, 2024 - Abstract #ADO2024ADO_564;    
    In monotherapy, the pan-PI3K inhibitor BKM120 (activity against p110 alpha, beta, gamma, and delta isoforms) is able to induce growth inhibition and apoptosis in most of the melanoma models tested to date, whereas BYL719, an alpha-specific inhibitor, has limited antitumor activity as monotherapy...Initial in vivo test results (in ovo) on chick chorioallantoic membrane (CAM) showed reduced tumor burden and micrometastases by using the p110alpha-specific BYL719 in combination with trametinib...These data show that the combination of PI3K inhibitors with MEK inhibitors could be a new therapeutic option for melanoma patients. By using PI3K?-selective inhibitors, potential side effects could be reduced compared to pan-PI3K inhibitors.