pan-AKT inhib 
Welcome,         Profile    Billing    Logout  
  Companies   Products    Products    Diseases    Trials    News 


123»
  • ||||||||||  Tribbles 1 (TRIB1) pseudokinase forms a complex with and activates Akt in GBM cells (Section 29) -  Mar 5, 2024 - Abstract #AACR2024AACR_5406;    
    TRIB1 can interact with different Akt isoforms in a cell type dependent manner thereby playing a role in their activation and consequent tumorigenic processes. Therefore, targeting TRIB1 mediated Akt activation could be considered a better therapeutic option over targeting Akt directly, which may decrease Akt's oncogenic activities without risking the toxicity associated with available Akt- specific inhibitors.
  • ||||||||||  Truqap (capivasertib) / Otsuka, AstraZeneca
    Journal:  A gain of function mutation in AKT1 increases hexokinase 2 and diminishes oxidative stress in meningioma. (Pubmed Central) -  Feb 26, 2024   
    Treatment with the conventional drug of choice AZD5363 (a pan AKT inhibitor) enhanced cell death and diminished HK2 levels in AKT1 mutants...By affecting metabolism, inflammation, and redox homeostasis AKT1-E17K confers a survival advantage in meningioma cells. Our findings suggest that targeting AKT-HK2 cross-talk to induce ROS-dependent cell death could be exploited as novel therapeutic approach in meningiomas.
  • ||||||||||  MK-2206 / Merck (MSD)
    Review, Journal:  Endoxifen downregulates AKT phosphorylation through protein kinase C beta 1 inhibition in ER?+ breast cancer. (Pubmed Central) -  Dec 20, 2023   
    ENDX's effects on AKT were phenocopied by siRNA-mediated PKC?1 knockdown or treatment with the pan-AKT inhibitor, MK-2206, while overexpression of constitutively active AKT diminished ENDX-induced apoptosis. These findings, which identify PKC?1 as an ENDX target, indicate that PKC?1/ENDX interactions suppress AKT signaling and induce apoptosis in breast cancer.
  • ||||||||||  MK-2206 / Merck (MSD)
    Journal:  AKT2 inhibition accelerates the acquisition of phagocytic ability in iPSCs-derived neutrophils. (Pubmed Central) -  Dec 17, 2023   
    The inhibition of AKT2 has been identified as the key mechanism underlying this acceleration. These results can make a substantial contribution to the development of strategies for the prompt production of clinically applicable iPSC-derived neutrophils, which can potentially lead to the management of severe infections associated with life-threatening neutropenia and the effective treatment of related health conditions in the future.
  • ||||||||||  Preclinical, Journal:  Safety and Toxicology Study of Hu7691, a Novel AKT Inhibitor, following Oral Administration in Rats. (Pubmed Central) -  Nov 24, 2023   
    The No Observed Effect Level (NOAEL) was determined to be no greater than 12.5 mg/kg/day. Based on the observed gender-related toxicity differences in preliminary trials, it is recommended that the high dose reference dose for male animals in formal experiments should not be less than 100 mg/kg/day, while for female animals, it should be less than 50 mg/kg/day.
  • ||||||||||  Journal:  Differential activation of AKT isoforms by growth factors in human myotubes. (Pubmed Central) -  Oct 29, 2023   
    For IGF-I stimulation, AKT1 was significantly higher than AKT2 at 45 and 60?min posttreatment (p?<?0.05 both) and significantly higher than AKT3 at all timepoints (p?<?0.05). Our findings reveal the differential phosphorylation patterns among the AKT isoforms and suggest a potential explanation for the regulatory role of AKT1 in skeletal muscle.
  • ||||||||||  miransertib (MK-7075) / Merck (MSD)
    Journal:  Kaposi's sarcoma-associated herpesvirus viral protein kinase augments cell survival. (Pubmed Central) -  Oct 22, 2023   
    vPK expression also inhibited the cytotoxicity of cisplatin in vitro and in vivo. Collectively, our findings demonstrate that vPK's ability to augment cell survival and promote angiogenesis is critically dependent on AKT signaling, which is relevant for future therapies for treating KSHV-associated cancers.
  • ||||||||||  Truqap (capivasertib) / Otsuka, AstraZeneca
    Capivasertib (C) + fulvestrant (F) for patients (pts) with aromatase inhibitor (AI)-resistant HR+/HER2 (Hall 401) -  Oct 6, 2023 - Abstract #ESMOAsia2023ESMO_Asia_413;    
    P3
    The most frequent AEs with C + F were diarrhoea (60.6% vs 11.3% P + F) and hyperglycaemia (57.7% vs 17.7%); the most frequent grade ?3 AEs were rash maculopapular (8.5% vs 0%), rash and diarrhoea (both 7.0% vs 0%); grade ?3 hyperglycaemia was 1.4% vs 0%. AEs leading to C/F discontinuation were reported in 11.3% for C + F vs 3.2% for P + F. Conclusions Similar to the Global population, the benefit
  • ||||||||||  SOX2 Deregulated Squamous Carcinomas Are Vulnerable to AKT3 Inhibition (Exhibit Hall) -  Jul 25, 2023 - Abstract #IASLCWCLC2023IASLC_WCLC_1212;    
    AEs leading to C/F discontinuation were reported in 11.3% for C + F vs 3.2% for P + F. Conclusions Similar to the Global population, the benefit Taken together, our work suggests that SOX2-amplified squamous cancers may be vulnerable to isoform-specific inhibition of AKT3.
  • ||||||||||  ipatasertib (RG7440) / Roche
    Preclinical, Journal:  Impact of AKT1 on cell invasion and radiosensitivity in a triple negative breast cancer cell line developing brain metastasis. (Pubmed Central) -  Jul 24, 2023   
    The impact of AKT1-knockout (AKT1_KO) and AKT-inhibition using Ipatasertib on MDA-MB-231 BR cells was assessed using in vitro cell proliferation and migration assays...AKT1-inhibition showed altered gene expression profile leading to modified cell migration, clonogenic survival and radioresistance in MDA-MB-231BR. We conclude, that AKT1-inhibition in combination with radiotherapy contribute to novel treatment strategies for breast cancer brain metastases.
  • ||||||||||  ipatasertib (RG7440) / Roche, nirogacestat (PF-03084014) / SpringWorks Therap, Rituxan (rituximab) / Biogen, Zenyaku Kogyo, Roche
    Journal:  DLBCL associated NOTCH2 mutations escape ubiquitin-dependent degradation and promote chemo-resistance. (Pubmed Central) -  May 26, 2023   
    Targeting CHOP-resistant DLBCL tumors with the Phase 3 clinical trial molecules nirogacestat, a selective g-secretase inhibitor, and ipatasertib, a pan-AKT inhibitor, synergistically promotes DLBCL death. These findings establish the rationale for therapeutic strategies aimed at targeting the oncogenic pathway activated in KLHL6- or NOTCH2-mutated DLBCL.
  • ||||||||||  vevorisertib (ARQ 751) / Merck (MSD)
    P1 data, Clinical Trial,Phase I, Journal, Metastases:  Phase 1b study of pan-AKT inhibitor vevorisertib alone or with paclitaxel or fulvestrant in PIK3CA/AKT/PTEN-mutated advanced solid tumors. (Pubmed Central) -  May 23, 2023   
    P1b
    These findings establish the rationale for therapeutic strategies aimed at targeting the oncogenic pathway activated in KLHL6- or NOTCH2-mutated DLBCL. Vevorisertib alone or with paclitaxel or fulvestrant had a manageable safety profile, and vevorisertib alone or with paclitaxel had minimal to modest antitumor activity in this patient population with PIK3CA/AKT/PTEN-mutated advanced solid tumors.
  • ||||||||||  ipatasertib (RG7440) / Roche
    Journal:  Proteogenomic characterization of ferroptosis regulators reveals therapeutic potential in glioblastoma. (Pubmed Central) -  May 13, 2023   
    Vevorisertib alone or with paclitaxel or fulvestrant had a manageable safety profile, and vevorisertib alone or with paclitaxel had minimal to modest antitumor activity in this patient population with PIK3CA/AKT/PTEN-mutated advanced solid tumors. In summary, our study characterized the proteogenomic landscape of ferroptosis regulators and identified that HSPB1 could be a candidate target for ferroptosis-inducing therapy strategy for GBM.
  • ||||||||||  capivasertib (AZD5363) / Otsuka, AstraZeneca
    Capivasertib (C) and fulvestrant (F) for patients (pts) with aromatase inhibitor (AI)-resistant HR+/HER2 (On Demand | Hall A; Poster Bd # 288) -  Apr 26, 2023 - Abstract #ASCO2023ASCO_3259;    
    P3
    Clinical trial information: NCT04305496. >aGroup terms (preferred terms): diarrhea (diarrhea, frequent bowel movements, gastrointestinal hypermotility); rash (rash, rash macular, maculopapular rash, rash papular, rash pruritic) and hyperglycemia (blood glucose increased, hyperglycemia).
  • ||||||||||  Piqray (alpelisib) / Novartis, capivasertib (AZD5363) / Otsuka, AstraZeneca
    Review, Journal:  Drugging the PI3K/AKT/mTOR Pathway in ER+ Breast Cancer. (Pubmed Central) -  Mar 16, 2023   
    Here, we review the role of the PI3K/AKT/mTOR pathway in ER+ advanced breast cancer, highlighting the genomic contexts in which the various inhibitors of this pathway may have superior activity. We also discuss selected trials with agents targeting the PI3K/AKT/mTOR and related pathways as well as the rationale supporting the clinical development of triple combination therapy targeting ER, CDK4/6 and PI3K/AKT/mTOR in ER+ advanced breast cancer.
  • ||||||||||  Mekinist (trametinib) / Novartis, capivasertib (AZD5363) / Otsuka, AstraZeneca
    Inhibition of both MAPK and AKT pathways overcomes resistance of NRAS-mutant melanoma stem cells to apoptosis (Section 16; Poster Board #4) -  Mar 14, 2023 - Abstract #AACR2023AACR_8380;    
    CD133 may therefore activate a survival pathway where (1) increased AKT phosphorylation and activation induces (2) BAD phosphorylation and inactivation, (3) decreases BAX activation, and (4) reduces caspases-3 and -9 activity and caspase-mediated PARP cleavage, leading to apoptosis suppression and drug resistance in melanoma. Targeting nodes of the AKT and MAPK survival pathways with both trametinib and AZD5363 highlights the potential for combination therapies for NRAS-mutant melanoma stem cells for the development of more effective treatments for patients with high-risk melanoma.
  • ||||||||||  Piqray (alpelisib) / Novartis
    Identification of novel regulators of response to PI3Ka inhibition in PIK3CA mutant gastric cancer (Section 15; Poster Board #27) -  Mar 14, 2023 - Abstract #AACR2023AACR_7350;    
    These data suggest that while CBFB loss is a key step in the development of PI3K? inhibitor resistance, PIK3CA mutant gastric tumors may be good candidates for clinical success with BYL719 alone and resistance could be prevented with combination with a PIM kinase inhibitor.
  • ||||||||||  miransertib (MK-7075) / Merck (MSD)
    Journal:  Identification of allosteric inhibitor against AKT1 through structure-based virtual screening. (Pubmed Central) -  Dec 16, 2022   
    Molecular docking and simulation analysis revealed that Bianthracene III (hit 1), 10-acetonyl Knipholonecyclooxanthrone (hit 2), Abyssinoflavanone VII (hit 5) and 8-c-p-hydroxybenzyldiosmetin (hit 6) had a better binding affinity, stability, and compactness than the reference compound. Notably, hit 1, hit 2 and hit 5 had molecular features required for allosteric inhibition.
  • ||||||||||  capivasertib (AZD5363) / Otsuka, AstraZeneca
    Analysis of single-cells using reverse phase protein array (RPPA) technology () -  Nov 30, 2022 - Abstract #DKK2022DKK_2135;    
    Background: Therapy with Capivasertib, a potent pan-AKT inhibi- tor, does not lead to response in all breast cancer patients with PIK3CA mutated tumor cells... We have established a new and highly sensitive method to measure expression and phosphorylation of treatment relevant proteins in single cells to measure activation of key cancer driving signaling pathways.
  • ||||||||||  MK-2206 / Merck (MSD), Kinenza (enzastaurin) / Denovo, Aytu BioPharma
    Endoxifen downregulates AKT phosphorylation through protein kinase C beta 1 in ER+/HER2- breast cancer (Hall 1) -  Oct 10, 2022 - Abstract #SABCS2022SABCS_946;    
    Taken together, these findings suggest that ENDX may exert anticancer activity via dual effects on blocking ERα as well as by targeting PKCβ1 for degradation, thus suppressing AKT signaling and induction of apoptosis. These preclinical findings will be studied in a planned neoadjuvant trial comparing ENDX with exemestane and ovarian function suppression (EVANGELINE) that will activate in the Fall of 2022.
  • ||||||||||  sirolimus / Generic mfg.
    Unexpected role for AKT signaling during motor skill learning in mice (SDCC Halls B-H) -  Oct 10, 2022 - Abstract #Neuroscience2022NEUROSCIENCE_12202;    
    We previously demonstrated in mice that the mechanistic target of rapamycin (mTOR) plays a critical role in the learning of a complex motor skill...These data were at a preliminary stage. Nevertheless, they raised the interesting possibility that Akt3 kinases play a critical role in the molecular processes of motor memory encoding.
  • ||||||||||  Ibrance (palbociclib) / Pfizer
    Preclinical, Journal:  miR-199a-3p increases the anti-tumor activity of palbociclib in liver cancer models. (Pubmed Central) -  Aug 30, 2022   
    At the molecular level, the combination caused the simultaneous decrease of the phosphorylation of both RB1 and of AKT. Our findings provide pre-clinical evidence for the efficacy of the combination miR-199a-3p/palbociclib as anti-HCC treatment or as a new approach to overcome sorafenib resistance.
  • ||||||||||  Journal:  AKT1 Transcriptomic Landscape in Breast Cancer Cells. (Pubmed Central) -  Jul 29, 2022   
    Representative experimental validation studies in two breast cancer cell lines showed a reasonable concurrence between the expression data from the RNA-sequencing and qRT-PCR or data from ex vivo inhibition of AKT1 activity in cancer patient-derived cells. In brief, findings presented here provide a resource for further understanding of AKT1-dependent modulation of gene expression in breast cancer cells and broaden the scope and significance of AKT1 targets and their functions.
  • ||||||||||  capivasertib (AZD5363) / Otsuka, AstraZeneca
    Review, Journal, PARP Biomarker:  "The emerging role of capivasertib in breast cancer". (Pubmed Central) -  May 4, 2022   
    Toxicity profile proved to be manageable with hyperglycemia (20-24%), diarrhea (14-17%) and maculopapular rash (11-16%) being the most common grade ≥3 adverse events. Ongoing Phase III trials of capivasertib in combination with fulvestrant (CAPItello-291), CDK4/6 inhibitor palbociclib (CAPItello-292) and paclitaxel (CAPItello- 290) will better clarify the therapeutic role of capivasertib in breast cancer.
  • ||||||||||  capivasertib (AZD5363) / Otsuka, AstraZeneca
    Preclinical efficacy of abiraterone plus capivasertib in mouse Pten-deficient prostate cancer (E-Poster Website) -  Mar 9, 2022 - Abstract #AACR2022AACR_6749;    
    Additionally, mice treated with combination therapy also had enrichments in genes sets associated to T cell, NK cell and as well as T cell activation, cytotoxicity, and interferon gamma signature. The findings from this study provide preclinical evidence for the efficacy of combination therapy with abiraterone plus capivasertib and provides insights into its immunomodulatory effects and influence on antitumor immunity.