MK-2206

Interventions utilizing a range of inhibitors at the in vitro level, including the PDGFR-β inhibitor AG1296, the PI3K inhibitor LY294002, the AKT inhibitor MK2206, and the FAK inhibitor Y15, demonstrated that E. multilocularis protoscoleces protein (EmP) induces angiogenesis through PDGFR/PI3K/AKT/FAK signaling pathway. Our findings provide new perspectives on how E. multilocularis infection triggers pathological angiogenesis in the host liver, and may provide a novel anti-angiogenic therapeutic strategy against E. multilocularis infection.

These subtypes exhibited distinct drug sensitivities (C1 sensitive to panobinostat, MK-2206, 17-AAG; C2 sensitive to venetoclax) and predicted immunotherapy responses (C1 potentially benefiting more from anti-PD-1)...Crucially, aberrant PKM2 overexpression was linked to imatinib (IM) resistance...To mitigate vMO toxicity, IL3-Lamp2b-engineered exosomes were developed, demonstrating efficient vMO loading, targeted delivery to leukemia cells, potent PKM splicing correction, significant IM resistance reversal, and minimal stromal cell toxicity. This work defines glycolysis-based AML subtypes with therapeutic implications and establishes engineered exosome-delivered vMO as a promising strategy to overcome drug resistance in hyper-glycolytic myeloid leukemia.

Combinatorial effects with hormone therapies (tamoxifen, fulvestrant, and letrozole) and the AKT inhibitor MK2206 were evaluated. Xanthene- and pyran-based hybrids-particularly SJ028, SJ064, and SJ078-showed strong antitumor activity through apoptosis induction, cell cycle arrest, and PI3K/AKT pathway modulation. Their preserved efficacy in resistant models and synergistic interactions with hormone therapies contrasted with the antagonism observed with AKT inhibition, highlighting their potential as promising candidates for the treatment of hormone-responsive and -resistant cancers.

Exosomal miR-20b-5p represses MASTL, remodels PI3K-AKT, and attenuates Ara-C responses in AML models. Seed-mutant reporters and 3'-UTR-independent rescue support target specificity. Findings are mechanistic and hypothesis-generating; clinical relevance requires confirmation in primary blasts and prospective validation.

This work demonstrates that the adipogenically differentiated MSCs enhance the survival and chemoresistance of AML cells by modulating metabolic and signaling pathways. It provides integrated insights into the microenvironment-driven mechanisms of AML drug resistance and presents potential therapeutic targets to enhance treatment efficacy.

The in vitro results were confirmed with in vivo mouse models. 4EGI-1 strongly inhibited NPC growth and metastasis, and 4EGI-1 may develop as the potential therapy for the treatment of metastatic NPC.

④ Histopathological analysis (H&E staining) of bone marrow and spleen tissues confirmed that the combined regimen decreased both tumor cell infiltration and the proportion of abnormal megakaryocytes in these organs. The combination of AKT inhibitor MK2206 and Ruxolitinib is effective at significantly ameliorating disease symptoms and reducing tumor infiltration in vivo in mice with a myeloproliferative tumor transplantation driven by a CALR gene mutation.

Furthermore, several targeted drugs, including MK-2206, pazopanib, JNK inhibitor VIII, PLX4720, and NU-7441, were associated with risk scores. This study identified five TRP-related biomarkers associated with RC prognosis, providing novel insights into the role of TRP channels in RC development. These findings may contribute to a deeper understanding of RC pathogenesis and offer potential targets for personalized therapy.

In this study, we investigated the effects of conventional chemotherapeutics, Cisplatin and 5-fluorouracil (5-FU), in combination with small molecule inhibitors (SMIs) targeting the PI3K/AKT signaling pathway, on NSCLC cell viability...Dose-response analyses were performed to determine the optimal concentrations of Cisplatin, 5-FU, the AKT inhibitor MK2206, and the PI3K inhibitor BKM120, both as monotherapies and in combination treatments...Mechanistic studies revealed that apoptosis induction was mediated through the apoptotic pathway regulated by the Bcl-2 family and activation of caspase-3 and caspase-6. These findings highlight the therapeutic potential of combining PI3K/AKT inhibitors with conventional chemotherapy to overcome resistance mechanisms in NSCLC.

HL-60 cells were treated with Idelalisib, MK-2206, and Everolimus, selective PI3K, AKT, and mTOR inhibitors, either individually or in combination. PI3K/AKT/mTOR inhibitors significantly induce autophagy-related gene expression in AML cells. These findings support combining such inhibitors with autophagy modulators as a potential strategy to improve AML treatment outcomes.

In vitro experiments using the AKT inhibitor MK‑2206 indicated that AKT is involved in the ER‑α36 knockdown‑induced changes in LMP and lysosomal localization in liver cancer cells. In summary, the present study revealed that ER‑α36 plays a role in regulating the autophagy and proliferation of liver cancer cells, which is associated with the modulation of AKT signaling, LMP and lysosome localization. These findings highlight an important role of ER‑α36 in liver tumorigenesis.

Taken together, this study provides the first experimental evidence to demonstrate that all G12 mutation cell lines are sensitive to VS6766 applied either alone or combined with 5-FU or AKT inhibitor.