PI3K inhib 
Welcome,         Profile    Billing    Logout  
 67 Companies  59 Products   59 Products   344 Diseases   342 Trials   12240 News 


«12...106107108109110111112113114115116...229230»
  • ||||||||||  Verzenio (abemaciclib) / Eli Lilly
    Clinical, Review, Journal:  Treatment of Luminal Metastatic Breast Cancer beyond CDK4/6 Inhibition: Is There a Standard of Care in Clinical Practice? (Pubmed Central) -  May 21, 2021   
    In addition, they are about to become a part of adjuvant treatment for patients with high-risk luminal disease based on positive results from the first randomized phase 3 trial on abemaciclib...Here we review current evidence from pro- and retrospective studies and give an outlook on future developments with respect to novel therapeutic agents, including oral SERD and AKT inhibitors, which have the potential to change the therapeutic landscape in the future. Furthermore, clinical treatment algorithms and current research will also be discussed.
  • ||||||||||  Arzerra (ofatumumab) / Novartis, Genmab, Opdivo (nivolumab) / Ono Pharma, BMS
    [VIRTUAL] Approaches to Therapy of Richter Syndrome (LEVEL 4, GRAND BALLROOM G-L) -  May 20, 2021 - Abstract #SOHO2021SOHO_170;    
    P2
    Conclusions Relapsed/refractory patients with CLL on novel agents are a new high-risk prognostic group with an extremely adverse outcome upon transformation. An international and common effort in developing preclinical models, prognosticators, biobanks, and databases should be pursued to improve outcomes in patients with RS.
  • ||||||||||  [VIRTUAL] Potential New Therapeutic Approaches for Myelofibrosis () -  May 20, 2021 - Abstract #SOHO2021SOHO_158;    
    Targeting the p53-HDM2 Axis KRT-232 is a first-in-class, potent, bioavailable inhibitor of HDM2 (key negative regulator of p53) that was assessed in a phase 2 study (KRT-232-101) and showed promising clinical efficacy and tolerability in TP53-wild type patients with MF who failed ruxolitinib treatment.17 A randomized phase 3 trial comparing KRT-232 (240 mg on days 1–7/28-day cycle) to BAT in MF patients refractory /resistant to JAK inhibitors has been launched...In the phase 2 study IMbark, the higher dose of imetelstat (9.4 mg/ kg) yielded a median overall survival of 29.9 months in patients with intermediate-2 or high-risk MF relapsed/refractory to JAK inhibitors.18 In light of the aforementioned promising result, a pivotal international phase 3 trial (IMpactMF) was launched to evaluate the survival advantage – an unprecedented trial endpoint for investigational MF medications – that imetelstat may confer to JAK-inhibitor-refractory MF patients.19 Conclusions The era of JAK1/2 inhibitor monotherapies in MF has ushered the way to the clinical development of a suite of promising novel medications spanning various biological mechanisms (for example, inhibitors of BET, HDM2, BCL-2/ BCL-XL, and telomerase, among others). Several highly promising candidates are currently evaluated in regulatory phase 3 clinical trials in the frontline and second line settings; these studies may lead to approval of novel medications that will significantly improve the current MF treatment paradigm.
  • ||||||||||  celecoxib oral / Generic mfg.
    Clinical, Journal:  Aberrant cell migration contributes to defective airway epithelial repair in childhood wheeze. (Pubmed Central) -  May 20, 2021   
    Importantly, the FDA-approved drug celecoxib - and its non-COX2-inhibiting analogue, dimethyl-celecoxib - stimulated the PI3K/Akt-integrin α5β1 axis and restored airway epithelial repair in cells from children with wheeze...Collectively, these results identify airway epithelial restitution via targeting the PI3K/Akt-integrin axis as a novel therapeutic avenue for childhood wheeze and asthma. We propose that the next step in the therapeutic development process should be a proof-of-concept clinical trial since relevant animal models to test the crucial underlying premise are unavailable.
  • ||||||||||  Journal:  GREB1 regulates PI3K/Akt signaling to control hormone-sensitive breast cancer proliferation. (Pubmed Central) -  May 20, 2021   
    Critically, growth suppression of estrogen-dependent breast cancer cells by GREB1 knockdown is rescued by expression of constitutively activated Akt. Together, these data identify a novel molecular function by which GREB1 regulates breast cancer proliferation through Akt activation and provides a mechanistic link between estrogen signaling and the PI3K pathway.
  • ||||||||||  Journal:  Identification of Novel Thiazolo[5,4-b]Pyridine Derivatives as Potent Phosphoinositide 3-Kinase Inhibitors. (Pubmed Central) -  May 20, 2021   
    Enzymatic Inhibition results showed that compound 19a inhibited PI3Kα, PI3Kγ, or PI3Kδ with a nanomolar IC value, but its inhibitory activity on PI3Kβ was approximately 10-fold reduced. Further docking analysis revealed that the N-heterocyclic core of compound 19a was directly involved in the binding to the kinase through the key hydrogen bonds interaction.
  • ||||||||||  Journal, IO biomarker:  Synergistic Carcinogenesis of HPV18 and MNNG in Het-1A Cells through p62-KEAP1-NRF2 and PI3K/AKT/mTOR Pathway. (Pubmed Central) -  May 20, 2021   
    Taken together, MNNG&HPV regulates autophagy and further accelerates cell appreciation by activating the p62/KEAP1/NRF2 and PI3K/AKT/mTOR pathway. MNNG&HPV may improve Het-1A cell autophagy to contribute to excessive cell proliferation, reduced apoptosis, and protection from oxidative damage, thus accelerating the process of cell malignant transformation and leading to cancerous cells.
  • ||||||||||  Journal:  SUMOylation modulates the stability and function of PI3K-p110β. (Pubmed Central) -  May 20, 2021   
    Finally, we show that the regulatory subunit p85β counteracts the conjugation of SUMO to p110β. In summary, our data reveal that SUMO is a novel p110β interacting partner with a positive effect on the activation of the PI3K pathway.
  • ||||||||||  ipatasertib (GDC-0068) / Roche, capivasertib (AZD5363) / Otsuka, AstraZeneca
    Review, Journal, PARP Biomarker, IO biomarker:  AKT Inhibitors: New Weapons in the Fight Against Breast Cancer? (Pubmed Central) -  May 20, 2021   
    As such, trials combining capivasertib and ipatasertib with CDK4/6 inhibitors, immune checkpoint inhibitors, and PARP inhibitors are currently ongoing. This review summarizes the available evidence on AKT inhibition in breast cancer, reporting both efficacy and toxicity data from clinical trials along with the available translational correlates and then focusing on the potential use of these drugs in new combination strategies.
  • ||||||||||  Journal, PARP Biomarker, IO biomarker:  Cardamonin inhibits the progression of oesophageal cancer by inhibiting the PI3K/AKT signalling pathway. (Pubmed Central) -  May 20, 2021   
    Moreover, the EC9706 xenograft model further confirmed that CAR can significantly inhibit tumour growth in vivo. In summary, CAR exhibited a strong anticancer effect on human oesophageal cancer cells and promoted apoptosis by inhibiting the PI3K/AKT signalling pathway, suggesting that CAR can be used as new strategy for oesophageal cancer treatment.
  • ||||||||||  Review, Journal:  Recent Updates on the Involvement of PI3K/AKT/mTOR Molecular Cascade in the Pathogenesis of Hyperproliferative Skin Disorders. (Pubmed Central) -  May 20, 2021   
    On the contrary, PI3K/AKT/mTOR role in AD is less characterized, even though recent evidence demonstrates the relevant function for mTOR pathway in the regulation of epidermal barrier formation and stratification. In this review, we provide the most recent updates on the role and function of PI3K/AKT/mTOR molecular axis in the pathogenesis of different hyperproliferative skin disorders, and highlights on the current status of preclinical and clinical studies on PI3K-targeted therapies.
  • ||||||||||  Clinical, Journal:  WDR81 regulates adult hippocampal neurogenesis through endosomal SARA-TGFβ signaling. (Pubmed Central) -  May 15, 2021   
    Inhibition of PI3K-III activity or suppression of SARA-dependent TGFβ signaling markedly ameliorated the defective adult neurogenesis in WDR81-deficient mice. Taken together, these findings not only uncover the requirement for the WDR81-SARA-TGFβ axis in adult hippocampal neurogenesis, but also suggest that defective adult hippocampal neurogenesis contributes to the etiology of WDR81-related neurological diseases.
  • ||||||||||  quercetin (LY294002) / Eli Lilly
    Preclinical, Journal:  Dahuang Zhechong pill attenuates CCl4-induced rat liver fibrosis via the PI3K-Akt signaling pathway. (Pubmed Central) -  May 15, 2021   
    In vitro experiments further demonstrated that DHZCP markedly suppressed HSCs proliferation by downregulating PI3K/Akt, which exerted a synergistic effect with the PI3K inhibitor LY294002. To sum up, our results confirmed that DHZCP exerted an antifibrotic effect in the animal model through inactivating the PI3K/Akt pathway, thus protecting rats from liver injury.
  • ||||||||||  chloroquine phosphate / Generic mfg., ibandronate sodium hydrate / Generic mfg.
    Journal:  Activation of autophagy during farnesyl pyrophosphate synthase inhibition is mediated through PI3K/AKT/mTOR signaling. (Pubmed Central) -  May 15, 2021   
    To sum up, our results confirmed that DHZCP exerted an antifibrotic effect in the animal model through inactivating the PI3K/Akt pathway, thus protecting rats from liver injury. These findings provide insights into the role of autophagy in the cardioprotective effects of IBAN and the molecular mechanisms underlying autophagy induction by IBAN.
  • ||||||||||  quercetin (LY294002) / Eli Lilly
    Preclinical, Journal:  Tolerance induced by DHPG postconditioning is mediated by the PI3K/Akt/GSK3β signalling pathway in an in vitro model of cerebral ischemia. (Pubmed Central) -  May 15, 2021   
    DHPG PostC also induces a transient increased in GSK3β phosphorylation and inactivation that is followed by nuclear accumulation of β-catenin, that probably lead to the up-regulation of neuroprotective genes. Our results propose GSK3β as new target for neuroprotection, therefore, we verified that the two GSK3β inhibitors N-(3-Chloro-4-methylphenyl)-5-(4-ni​trophenyl)-1,3,4-oxadiazol-2-amine (TC-G 24) and LiCl are neuroprotective agents in OGD and also can be used as PostC agents.
  • ||||||||||  Journal:  Unsaturated polyurethane films grafted with enantiomeric polylysine promotes macrophage polarization to a M2 phenotype through PI3K/Akt1/mTOR axis. (Pubmed Central) -  May 15, 2021   
    The CD44 and integrins of macrophages participate in the polarization process probably by activating focal adhesion kinase (FAK) and Rho-associated protein kinase (ROCK), and downstream PI3K/Akt1/mTOR signal axis to up regulate M2 related gene expression. This study confirms for the first time that polylysine coating is an effective method to regulate the immune response of biomaterials, and the polylysine-modified thermoplastic PPFU with the advantage to promote M2 polarization may be applied widely in regenerative medicine.
  • ||||||||||  Journal, Cancer stem cells:  Cancer stem cell generation by silenced MAPK enhancing PI3K/AKT signaling. (Pubmed Central) -  May 15, 2021   
    The feasibility of this combination will be explained in this hypothesis through the reports published somewhere. Generation of cancer stem cells using embryonic stem cells/iPSCs will bring new theory in the mechanisms of tumorigenesis and assist drug screening that applies for the precision medicines for individuals.