AKT 

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  • ||||||||||  LY294002 / Eli Lilly, erastin - Whitehead Institute for Biomedical Research, Dana / Farber Cancer Institute, Columbia University, Prolexys
    Journal:  The roles of autophagy, ferroptosis and pyroptosis in the anti-ovarian cancer mechanism of harmine and their crosstalk. (Pubmed Central) -  Mar 23, 2024   
    LY294002 and siFOXO3 rescued the inhibition of the PI3K/AKT/mTOR/FOXO3 signalling pathway and the promotion of autophagy by Har...Interestingly, pretreatment with chloroquine (CQ), erastin, rapamycin (Rap), or ferrostatin-1 (Fer-1) increased or reversed the ferroptosis and pyroptosis promoted by Har, respectively...In conclusion, Har exerts its anti-ovarian cancer effect not only by promoting autophagy by regulating the PI3K/AKT/mTOR/FOXO3 signalling pathway but also by promoting ferroptosis and pyroptosis. Additionally, there is complex crosstalk between autophagy, ferroptosis, and pyroptosis in ovarian cancer.
  • ||||||||||  Epidaza (chidamide) / Chipscreen, Meiji Seika, Eisai, HUYA Bioscience
    Journal:  Design, synthesis and activity evaluation of arctigenin derivatives with HDAC inhibition activity. (Pubmed Central) -  Mar 21, 2024   
    Among them, compound B7 exhibited significantly higher antiproliferative activity in the MV411 cell line compared to the positive control, tucidinostat...Further mechanistic studies indicated that compound B7 induced apoptosis through the Caspase-3 pathway in MV411 cells and enhanced histone acetylation levels in the MV411 cell line. These findings highlight the broad potential application of these arctigenin derivatives in cancer therapy.
  • ||||||||||  MK-2206 / Merck (MSD)
    Journal:  Promotion of non-small cell lung cancer tumor growth by FHL2 via inducing angiogenesis and vascular permeability. (Pubmed Central) -  Mar 20, 2024   
    Vascular endothelial growth factor A (VEGFA) enzyme-linked immunosorbent assay (ELISA) assay, Western blot analysis, and MK-2206 were used to investigate the specific mechanism mediated by FHL2...We further confirmed that FHL2 also promoted NSCLC tumor growth in vivo. Our study revealed the role of FHL2 in NSCLC and the mechanism by which FHL2 promotes NSCLC tumorigenesis, providing novel insights into targeted therapy for NSCLC.
  • ||||||||||  metformin / Generic mfg.
    Journal:  Just a spoonful of metformin helps the medicine go down. (Pubmed Central) -  Mar 19, 2024   
    To tackle this mechanism of resistance, the authors added the PKC inhibitor enzastaurin to their drug combination and showed that this triple therapy led to improved survival. This approach paves the way for improved outcomes for patients with DIPG and other brain tumors.
  • ||||||||||  Kinenza (enzastaurin) / Denovo, Aytu BioPharma, paxalisib (GDC-0084) / Kazia
    Journal:  PI3K/mTOR is a therapeutically targetable genetic dependency in diffuse intrinsic pontine glioma. (Pubmed Central) -  Mar 18, 2024   
    Therapeutic adaptation was assessed using spatial transcriptomics and ATAC-sequencing, identifying changes in myelination and tumor immune microenvironment crosstalk. Together, we have identified a clinically relevant DIPG therapeutic combinatorial approach.
  • ||||||||||  ABTL0812 / Ability Pharma
    Trial completion, Trial completion date, Trial primary completion date, Combination therapy, Metastases:  PanC-ASAP: ABTL0812 in Combination With FOLFIRINOX for First-line Treatment of Metastatic Pancreatic Study (clinicaltrials.gov) -  Mar 17, 2024   
    P1/2,  N=150, Completed, 
    Trial completion date: Dec 2024 --> Jun 2024 Trial completion date: Sep 2028 --> Jan 2024 | Trial primary completion date: Dec 2024 --> Jan 2024 | Recruiting --> Completed
  • ||||||||||  Kinenza (enzastaurin) / Denovo, Aytu BioPharma, Rydapt (midostaurin) / Novartis
    Review, Journal:  Marine-Derived Bisindoles for Potent Selective Cancer Drug Discovery and Development. (Pubmed Central) -  Mar 17, 2024   
    Consequently, they exhibit immense potential in the field of anti-tumor drug development, especially in the field of anti-tumor drug resistance. In the future, these compounds may serve as promising leads in the discovery and development of novel cancer therapeutics.
  • ||||||||||  LY294002 / Eli Lilly
    Journal:  PI3K/AKT mediated De novo fatty acid synthesis regulates RIG-1/MDA-5-dependent type I IFN responses in BVDV-infected CD8+T cells. (Pubmed Central) -  Mar 13, 2024   
    Treatment with the FASN inhibitor C75 significantly reduces the phosphorylation of PI3K and AKT in BVDV-infected CD8+ T cells, while inhibition of PI3K with LY294002 decreases FASN expression...Moreover, FASN inhibitors induce TBK-1 phosphorylation through the activation of RIG-1 and MDA-5, subsequently activating IRF-3 and ultimately enhancing the IFN-1 response. In conclusion, our study demonstrates that BVDV infection activates the PI3K/AKT pathway to boost de novo fatty acid synthesis, and inhibition of FASN suppresses BVDV replication by activating the RIG-1/MDA-5-dependent IFN response.
  • ||||||||||  Turalio (pexidartinib) / Daiichi Sankyo
    Enrollment closed, Phase classification, Trial completion date, Combination therapy:  PLX3397 Plus Sirolimus in Unresectable Sarcoma and Malignant Peripheral Nerve Sheath Tumors (clinicaltrials.gov) -  Mar 13, 2024   
    P1/2,  N=43, Active, not recruiting, 
    Our data demonstrated, for the first time, that oxidative stress and the AKT/mTOR pathway plays a critical role in Light-induced apoptosis and autophagic cell death in mice and HT-22 cells. Recruiting --> Active, not recruiting | Phase classification: P2 --> P1/2 | Trial completion date: Mar 2024 --> Jun 2024
  • ||||||||||  afuresertib (LAE002) / Laekna Therap
    Trial completion date:  PROFECTA-II: Study With Afuresertib and Paclitaxel in Platinum Resistant Ovarian (clinicaltrials.gov) -  Mar 12, 2024   
    P2,  N=141, Active, not recruiting, 
    Recruiting --> Active, not recruiting | Phase classification: P2 --> P1/2 | Trial completion date: Mar 2024 --> Jun 2024 Trial completion date: Nov 2024 --> Jun 2024
  • ||||||||||  dordaviprone (ONC201) / Chimerix
    Trial completion date, Trial initiation date, Trial primary completion date:  A Study of ONC201 for Refractory Meningioma (clinicaltrials.gov) -  Mar 12, 2024   
    P1,  N=27, Not yet recruiting, 
    Our data endorsed the use of chidamide in patients pretreated with CDK4/6 inhibitors and patients treated with different endocrine combinations. Trial completion date: Jan 2027 --> Apr 2027 | Initiation date: Jan 2024 --> Apr 2024 | Trial primary completion date: Jan 2026 --> Apr 2026
  • ||||||||||  Prezista (darunavir) / J&J, Xalkori (crizotinib) / Pfizer, Viracept (nelfinavir) / ViiV Healthcare, Roche
    New approach for predicting drug-resistant mutations | Poster Board #1820 (In-person; Poster Board #1820; Hall C (Ernest N. Morial Convention Center)) -  Mar 12, 2024 - Abstract #ACSSp2024ACS_Sp_9898;    
    The ?FV score, a product of variability coefficients and atomic fluctuations, accurately identified hotspots for FDA-approved drugs-nelfinavir, darunavir and mainly crizotinib, offering promise in delaying resistance onset. Despite some limitations, particularly in detecting mutations beyond binding sites, this method presents an intriguing avenue for predicting novel clinical mutations, shaping the future of drug resistance research.
  • ||||||||||  LY294002 / Eli Lilly
    Journal:  Effect of gold-conjugated resveratrol nanoparticles on glioma cells and its underlying mechanism. (Pubmed Central) -  Mar 10, 2024   
    In addition, the inhibitory role of Rsv-AuNPs in the PI3K/AKT/mTOR signaling pathway was verified by using PI3K inhibitor LY294002...The present study found that Rsv-AuNPs inhibited the proliferation, migration, and invasion of U87 cells and induced apoptosis by inhibiting the activation of PI3K/AKT/mTOR signaling pathway. In the future, Rsv-AuNPs might be applied to the clinical treatment of glioma through more in-depth animal and clinical research.
  • ||||||||||  LY294002 / Eli Lilly
    Journal:  TXNIP Regulates NLRP3 Inflammasome-Induced Pyroptosis Related to Aging via cAMP/PKA and PI3K/Akt Signaling Pathways. (Pubmed Central) -  Mar 9, 2024   
    Furthermore, we conducted experiments to modulate the improvement of TXNIP on NLRP3 inflammasome-induced pyroptosis, that is, the PI3K activator 740 Y-P and the PKA activator DC2797 inhibited the effect, while the PI3K inhibitor LY294002 and the PKA inhibitor H89 enhanced the effect. In conclusion, our study demonstrated that TXNIP regulates NLRP3 inflammasome-induced pyroptosis in HT-22 cells related to aging via the PI3K/Akt and cAMP/PKA pathways.
  • ||||||||||  LY294002 / Eli Lilly
    ANGIOTENSIN II PROMOTES PODOCYTE APOPTOSIS THROUGH THE MODULATION OF CD2AP AND AMPK (SUN-044; Exhibition Hall and Main Foyer) -  Mar 8, 2024 - Abstract #ISNWCN2024ISN_WCN_863;    
    LY294002, a PI3-K inhibitor, reduced CD2AP suppressed by Ang II. Our findings suggest that Ang II induces the relocation and suppression of podocyte CD2AP and AMPKa via Ang II type 1 receptor and through the inhibition of PI3-K signaling, which trigger podocyte apoptosis induced by Ang II.
  • ||||||||||  Turalio (pexidartinib) / Daiichi Sankyo
    Microglial-targeted Gene Therapy: Developing a Disease Modifying Treatment for ALSP Associated with CSF1R Mutations (ALSP-CSF1R) (Colorado Convention Center | Exhibit Hall B-E) -  Mar 8, 2024 - Abstract #AAN2024AAN_4529;    
    Currently, there is no disease-modifying therapy for ALSP-CSF1R and the use of available drugs is limited to managing disease associated symptoms. Our findings suggest that PR009 has the potential to treat the underlying cause of ALSP-CSF1R by expressing hTREM2 in the microglia of patients, resulting in restoration of microglial function and survival.
  • ||||||||||  Zolinza (vorinostat) / Merck (MSD), Epidaza (chidamide) / Chipscreen, Meiji Seika, Eisai, HUYA Bioscience, Farydak (panobinostat) / Secura Bio
    Review, Journal, Epigenetic controller:  Current treatment strategies targeting histone deacetylase inhibitors in acute lymphocytic leukemia: a systematic review. (Pubmed Central) -  Mar 7, 2024   
    Preclinical research has identified chidamide as a potential agent for investigation in more clinical trials in the future. In conclusion, histone deacetylase inhibitors play a significant role in the chemotherapy-free landscape in cancer treatment, particularly in acute lymphocytic leukemia.
  • ||||||||||  LY294002 / Eli Lilly
    Preclinical, Journal:  Echinacoside alleviates glucocorticoid induce osteonecrosis of femoral head in rats through PI3K/AKT/FOXO1 pathway. (Pubmed Central) -  Mar 6, 2024   
    Validation of the PI3K inhibitor (LY294002) and molecular docking of Ech and PI3K/AKT further indicated that Ech could directly enhance PI3K/AKT activity to alleviate Dex-induced inhibition...Our results provide robust evidence that PI3K/AKT/FOXO1 plays a crucial role in the development of SONFH. Moreover, Ech may be a promising candidate drug for the treatment of SONFH.