PI3K inhib 
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  • ||||||||||  Review, Journal:  Therapeutic landscape of advanced HER2-positive breast cancer in 2022. (Pubmed Central) -  Oct 20, 2022   
    Another newer agent approved for third- or later-line therapy in the metastatic setting is margetuximab, an Fc-engineered anti-HER2 monoclonal antibody, in combination with chemotherapy. Other novel agents currently under clinical trials are the drugs that indirectly target HER2, including immune cell cycle inhibitors, PI3K/mTOR inhibitors, and immunotherapy agents.
  • ||||||||||  Piqray (alpelisib) / Novartis, Mekinist (trametinib) / Novartis, Tafinlar (dabrafenib) / Novartis
    TUMOUR-AGNOSTIC INDICATIONS: ARE WE MOVING TOWARDS A MUTATION-DRIVEN APPROACH IN PRECISION ONCOLOGY? () -  Oct 19, 2022 - Abstract #AIOM2022AIOM_99;    
    P2
    These results suggest that MAPs based on an agnostic approach may offer a viable therapeutic oppor- tunity for pts affected by tumors harboring actionable mutations and lacking therapeutic alternatives. Despite further data are needed to confirm the effectiveness of this approach, MAPs have a crucial role both in patient’s care and generation of real-world data that might support clini- cal practice and future areas of investigation.
  • ||||||||||  parsaclisib (INCB50465) / Incyte
    Trial completion date:  CITADEL-203: A Study of INCB050465 in Relapsed or Refractory Follicular Lymphoma (clinicaltrials.gov) -  Oct 19, 2022   
    P2,  N=126, Active, not recruiting, 
    Silibinin might be a good candidate for PCO prevention; however, functional evaluation of silibinin using in vivo models is a pre-requisite. Trial completion date: Mar 2023 --> Jun 2023
  • ||||||||||  Review, Journal, BRCA Biomarker, PD(L)-1 Biomarker, IO biomarker:  Breast cancer: an up-to-date review and future perspectives. (Pubmed Central) -  Oct 18, 2022   
    Innovation technologies of precision medicine may guide individualized treatment escalation or de-escalation in the future. In this review, we summarized the latest scientific information and discussed the future perspectives on breast cancer.
  • ||||||||||  Piqray (alpelisib) / Novartis
    Trial completion date, Combination therapy, Metastases:  BYL719 and Letrozole in Post-Menopausal Patients With Hormone Receptor-Positive Metastatic Breast Cancer (clinicaltrials.gov) -  Oct 18, 2022   
    P1,  N=46, Active, not recruiting, 
    While copanlisib did not result in tumor regression, more data are needed to fully explore the role of the PI3K pathway in the pathogenesis of osteosarcoma. Trial completion date: Aug 2022 --> Oct 2023
  • ||||||||||  Preclinical, Journal:  Insilco and Invitro approaches identify novel dual PI3K/AKT pathway inhibitors to control acute myeloid leukemia cell proliferations. (Pubmed Central) -  Oct 16, 2022   
    Computational screening, enzyme inhibition and cell proliferation assays show compound C16,5-{[(1,3-dioxo-1H-benzo[de]isoquinolin-2(3H)-yl)amino]methylene}-1-phenyl-2,4,6(1H,3H,5H)-pyrimidinetrione has better affinity for PI3KCG, delta, and AKT kinases compared to their respective known/established inhibitors, and has significant anti-cell proliferation activity in AML cells with a GI values of 77.25 nM and 49.65 nM in THP-1 and HL-60 cells, respectively. This work proposes a novel dual inhibitor that selectively targets PI3K/AKT and suppresses cell proliferation in AML cells as a potential lead molecule for treating AML cancers.
  • ||||||||||  Review, Journal:  Novel approaches to antiplatelet therapy. (Pubmed Central) -  Oct 16, 2022   
    Here we review the pharmacologic approaches to platelet inhibition currently available and in development for their effects on platelet activation in vitro and on thrombosis in animal models and in humans. An ideal antithrombotic agent should selectively target events crucial for pathological thrombus formation without affecting hemostasis, an objective so far not achieved: if one or more of the novel agents in development will reach this goal this will represent a great step forward in the prevention of ischemic cardiovascular events.
  • ||||||||||  Genetic and Physiological Effects of Insulin-Like Growth Factor-1 (IGF-1) on Human Urate Homeostasis (Exhibit Hall, Orange County Convention Center, West Building) -  Oct 13, 2022 - Abstract #KIDNEYWEEK2022KIDNEY_WEEK_3745;    
    Conclusion The combined results of infusion, genetics, and transport experiments suggest that IGF-1 reduces SU by activating urate secretory transporters and inhibiting insulin’s action. IGF-1 antagonizes the effects of insulin on urate transporters, indicating complex interactions in hyperuricemia associated with metabolic syndrome and hyperinsulinemia.
  • ||||||||||  Tuning Kidney Organoids to Generate High-Fidelity Proximal Tubule Cells (Exhibit Hall, Orange County Convention Center, West Building) -  Oct 13, 2022 - Abstract #KIDNEYWEEK2022KIDNEY_WEEK_1227;    
    As such, these studies inform in vitro nephrogenesis strategies building regenerative therapeutics. Percentage of total read counts from day 18 bulk RNA-seq of whole-organoid samples (n = 2).
  • ||||||||||  LY294002 / Eli Lilly
    Aldehyde Dehydrogenase 2 Alleviates Mitochondrial Dysfunction by Regulating Aerobic Glycolysis via PI3K/AKT/mTOR Pathway in AKI (Exhibit Hall, Orange County Convention Center, West Building) -  Oct 13, 2022 - Abstract #KIDNEYWEEK2022KIDNEY_WEEK_1012;    
    Furthermore, LY294002 partially reversed the cell apoptosis percentage (15.50%± 0.67 versus 19.50% ± 0.68, P <0.05) of ALDH2 knockdown in MA-induced HK2 cells. Conclusion ALDH2 prevented tubular injury and apoptosis by rescuing mitochondrial dysfunction and aerobic glycolysis via the PI3K/AKT/mTOR pathway in cisplatin and MA-induced AKI.
  • ||||||||||  Journal:  VEGF-A promotes the motility of human melanoma cells through the VEGFR1-PI3K/Akt signaling pathway. (Pubmed Central) -  Oct 13, 2022   
    These findings suggest that the motility of melanoma cells is regulated by signals mediated through the PI3K/Akt kinase pathway with the activation of VEGFR1 tyrosine kinase by VEGF. Thus, the downregulation of signaling via VEGF-A/VEGFR1 might be an effective therapeutic approach that could prevent the progression of malignant melanoma.
  • ||||||||||  Piqray (alpelisib) / Novartis
    Review, Journal:  Development of PI3Kα inhibitors for tumor therapy. (Pubmed Central) -  Oct 13, 2022   
    In this review, we briefly describe PI3Kα and its role in tumorigenesis, summarize the clinical trial results of some PI3Kα inhibitors as well as the synthetic routes of alpelisib, and finally give our proposal for the development of novel PI3Kα inhibitors for tumor therapy. HighlightsWe summarize the progress of PI3Kα and PI3Kα inhibitors in cancer from the second half of the 20th century to the present.We describe the clinical trial results of PI3Kα inhibitors as well as the synthetic routes of the only approved PI3Kα inhibitor alpelisib.Crystal structure of alpelisib bound to the PI3Kα receptor binding domain.This review gives proposal for the development of novel PI3Kα inhibitors and will serve as a complementary summary to other reviews in the research field of PI3K inhibitors.
  • ||||||||||  Preclinical, Journal:  The Effect of Melatonin on OCT4 Expression and Granulosa Cell Growth in Female Mice. (Pubmed Central) -  Oct 12, 2022   
    In conclusion, this study shows that melatonin inhibits ovarian cell development by downregulating the OCT4 expression level, which is possibly mediated by inhibiting the PI3K/Akt and GSK3β/β-catenin pathway. Melatonin attenuates the effects of gonadotropin on ovarian granulosa cells as a negative regulator.
  • ||||||||||  Tagrisso (osimertinib) / AstraZeneca
    Journal:  AZD9291 suppresses proliferation and migration of nasopharyngeal carcinoma cells by inhibiting the PI3K-AKT-mTOR pathway (Pubmed Central) -  Oct 11, 2022   
    Our results demonstrate how LMDS-1 and -2 are likely to work as TRKB agonists to exert neuroprotection in Aβ cells, which may shed light on the potential application in therapeutics of AD. AZD9291 suppresses proliferation and attenuates repair and migration capacities of nasopharyngeal carcinoma cells by inhibiting the EGFR/PI3K/AKT/mTOR signaling pathway, suggesting the potential value of AZD9291 in the treatment of nasopharyngeal carcinoma.
  • ||||||||||  tamoxifen / Generic mfg.
    Breast cancer microenvironment change after neoadjuvant endocrine treatment (Hemisfair Ballroom 1&2) -  Oct 10, 2022 - Abstract #SABCS2022SABCS_1823;    
    NET influences the composition and/or functional state of the infiltrating immune cells. Furthermore, changes in the immune micro-environment are also associated with treatment response.
  • ||||||||||  MK-2206 / Merck (MSD), ipatasertib (RG7440) / Roche, capivasertib (AZD5363) / Otsuka, AstraZeneca
    Development of novel inhibitors of the serum/glucocorticoid induced kinase (SGK) family to address limitations of AKT/PI3K/mTOR inhibitors in breast cancer (Hall 1) -  Oct 10, 2022 - Abstract #SABCS2022SABCS_1176;    
    For example, strong Bliss synergy index scores > 18 were obtained with different SGK1 inhibitors when combined with either AKT inhibitors MK-2206, ipatasertib, or capivasertib, in the JIMT-1 breast cancer cell line, which is a model of resistance to AKT, PI3K, and HER2-directed therapies. These results suggest that the combination of SGK with AKT inhibitors could be an effective therapeutic strategy to alleviate toxicities associated with AKT/PI3K/mTOR inhibitors by lowering their required dose, while maintaining anti-tumor activity and delaying the development of resistance.
  • ||||||||||  STX-478 / Scorpion Therap
    STX-478, a mutant-selective PI3Kα H1047X inhibitor clinical candidate with a best-in-class profile: Pharmacology and therapeutic activity as monotherapy and in combination in breast cancer xenograft models (Hall 1) -  Oct 10, 2022 - Abstract #SABCS2022SABCS_1094;    
    When combined with fulvestrant, lapatinib, or abemaciclib, STX-478 demonstrated synergistic anti-proliferative activity in cell lines with relevant ER/HER2 status...In the T47D (PI3Kα H1047R) breast cancer model, STX-478 (100 mg/kg) monotherapy caused tumor regression whereas alpelisib caused only stasis...In an ER+/HER2+ PDX model (PI3Kα H1047R/R108H), palbociclib and STX-478 (100 mg/kg) monotherapy resulted in similar efficacy while the combination was well tolerated and yielded tumor regression...The significant CNS exposure of STX-478 is expected to enable this treatment for patients with brain tumors and brain metastases not afforded by existing options. STX-478 is currently in IND enabling studies and is expected to enter human clinical trials in 2023.
  • ||||||||||  Piqray (alpelisib) / Novartis
    Novel targeting of semaphorin 7a-mediated survival signaling in ER+ breast cancer (Hall 1) -  Oct 10, 2022 - Abstract #SABCS2022SABCS_945;    
    Also, addition of exogenous SEMA7A protein reduces SIM2s expression and promoter activity. Since SIM2s correlates with inhibition of PI3K/Akt signaling and decreased SEMA7A, and SEMA7A promotes survival signaling, we are investigating additional therapeutic strategies to prevent endocrine therapy resistance via direct inhibition of SEMA7A and/or restoration of SIM2s, including inhibition of COX-2 and Akt signaling.
  • ||||||||||  Ibrance (palbociclib) / Pfizer, Kisqali (ribociclib) / Novartis, Verzenio (abemaciclib) / Eli Lilly
    CDK4/6 inhibitors modulate the ubiquitin–proteasome pathway in ER+ breast cancer by downregulation of UBE2C/S/T (Hall 1) -  Oct 10, 2022 - Abstract #SABCS2022SABCS_754;    
    We further demonstrate the UBE2C/UBE2T expression levels are associated with breast cancer survival, and HR(+) breast cancer cells demonstrate dependence on the UBE2C. Our study suggests a novel link between CDK4/6 inhibitor and UPP pathway, adding to the potential mechanisms of their clinical efficacy in cancer.
  • ||||||||||  Herceptin (trastuzumab) / Roche, Perjeta (pertuzumab) / Roche
    ESAM reduces anti-HER2 therapy sensitivity by activating mTOR pathway in HER2 positive breast cancer (Hall 1) -  Oct 10, 2022 - Abstract #SABCS2022SABCS_495;    
    High ESAM expression is associated with poor prognosis in patients with HER2 positive breast cancer. ESAM can activate mTOR pathway, promote cell proliferation and reduce the sensitivity of HER2 positive breast cancer cells to trastuzumab and pertuzumab, which can be inhibited by the application of PI3K/mTOR inhibitors.
  • ||||||||||  Piqray (alpelisib) / Novartis
    Potentiating alpelisib in PI3K pathway overactive triple negative breast cancers (Hall 1) -  Oct 10, 2022 - Abstract #SABCS2022SABCS_480;    
    Testing with in vivo models of each drug combination has thus far confirmed that each is synergistic per CDI metrics. Those combinations are currently being tested for efficacy in the metastatic setting with a set of basal-like PDXs.