ReviewCurrent medicinal chemistry2011
Novel inhibitors of AKT: assessment of a different approach targeting the pleckstrin homology domain.
Review in Current medicinal chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed.
- Review
- An active allosteric mechanism in ASAP1-mediated Arf1 GTP hydrolysis redefines PH domain function.Nature communications · 2025Article
- Redefining the role of IL-18 in post-surgical recovery and sepsis: a key mediator of inflammation resolution.Journal of translational medicine · 2025Article
- The PH domain in the ArfGAP ASAP1 drives catalytic activation through an unprecedented allosteric mechanism.bioRxiv : the preprint server for biology · 2024Article
- Capturing Autoinhibited PDK1 Reveals the Linker's Regulatory Role, Informing Innovative Inhibitor Design.Journal of chemical information and modeling · 2024Article
- Structural investigation of Trypanosoma cruzi Akt-like kinase as drug target against Chagas disease.Scientific reports · 2024Article
- Taenia solium cysticerci's extracellular vesicles Attenuate the AKT/mTORC1 pathway for Alleviating DSS-induced colitis in a murine model.Journal of extracellular vesicles · 2024Article
- Targeting the PI3K/AKT/mTOR and RAF/MEK/ERK pathways for cancer therapy.Molecular biomedicine · 2022Review
- Reining in BTK: Interdomain Interactions and Their Importance in the Regulatory Control of BTK.Frontiers in cell and developmental biology · 2021Review
- Inositol Polyphosphate-Based Compounds as Inhibitors of Phosphoinositide 3-Kinase-Dependent Signaling.International journal of molecular sciences · 2020Review
- The structural determinants of PH domain-mediated regulation of Akt revealed by segmental labeling.eLife · 2020Article
- Discovery of Small Molecules That Target the Phosphatidylinositol (3,4,5) Trisphosphate (PIPMolecular pharmacology · 2020Article
- Allosteric AKT Inhibitors Target Synthetic Lethal Vulnerabilities in E-Cadherin-Deficient Cells.Cancers · 2019Article
- Activation of Insulin Signaling in Adipocytes and Myotubes byNutrients · 2019Article
- Discovery of a small-molecule inhibitor of specific serine residue BAD phosphorylation.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Inositol-C2-PAF acts as a biological response modifier and antagonizes cancer-relevant processes in mammary carcinoma cells.Cellular oncology (Dordrecht, Netherlands) · 2018Article
- RBL2/p130 is a direct AKT target and is required to induce apoptosis upon AKT inhibition in lung cancer and mesothelioma cell lines.Oncogene · 2018Article
- Identification of 4-phenylquinolin-2(1H)-one as a specific allosteric inhibitor of Akt.Scientific reports · 2017Article
- Acetyl-lupeolic acid inhibits Akt signaling and induces apoptosis in chemoresistant prostate cancer cellsOncotarget · 2017Article
- Inhibitory effect of Ginkgol C17:1 on the biological behavior of tumor cells.Oncology letters · 2017Article
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Abstract
Protein kinase B/AKT plays a central role in cancer. The serine/threonine kinase is overexpressed or constitutively active in many cancers and has been validated as a therapeutic target for cancer treatment. However, targeting the kinase activity has revealed itself to be a challenge due to non-selectivity of the compounds towards other kinases. This review summarizes other approaches scientists have developed to inhibit the activity and function of AKT. They consist in targeting the pleckstrin homology (PH) domain of AKT. Indeed, upon the generation of 3-phosphorylated phosphatidylinositol phosphates (PI3Ps) by PI3-kinase (PI3K), AKT translocates from the cytosol to the plasma membrane and binds to the PI3Ps via its PH domain. Thus, several analogs of PI3Ps (PI Analogs or PIAs), alkylphospholipids (APLs), such as edelfosine or inositol phophates (IPs) have been described that inhibit the binding of the PH domain to PI3Ps. Recent allostertic inhibitors and small molecules that do not bind the kinase domain but affect the kinase activity of AKT, presumably by interacting with the PH domain, have been also identified. Finally, several drug screening studies spawned novel chemical scaffolds that bind the PH domain of AKT. Together, these approaches have been more or less sucessfull in vitro and to some extent translated in preclinical studies. Several of these new AKT PH domain inhibitors exhibit promising anti-tumor activity in mouse models and some of them show synergy with ionizing radiation and chemotherapy. Early clinical trials have started and results will attest to the validity and efficacy of such approaches in the near future.
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