MK-2206 / Merck (MSD) - LARVOL DELTA

Concurrent Inhibition of AKT and GLUT1 Reveals Endpoint-Specific Effects on Glucose Metabolism and Cell Death in HepG2 Hepatocyte-Derived Cells. (PubMed, Biomedicines) - "MK-2206, a potent allosteric AKT inhibitor, and BAY-876, a highly selective GLUT1 inhibitor, represent targeted approaches to disrupt these processes... Dual AKT/GLUT1 targeting produces endpoint-specific patterns of pharmacological interaction on insulin-responsive metabolism, proliferation, and cell death in HepG2 hepatocyte-derived cells, distinguishing combination-specific effects from AKT-driven effects. These findings support an endpoint-specific pharmacological framework in which AKT signaling and BAY-876-mediated GLUT1 pharmacological effects jointly influence glucose handling and cell fate in a hepatocyte-derived model."

Journal • Diabetes • ANXA5 • CASP3 • SLC2A1

Apigenin activates AKT1 to coordinate MTOR-mediated anti-apoptosis and FOXO3-driven antioxidant defense in calcium oxalate nephropathy. (PubMed, Int J Surg) - "The functional role of AKT1 was further examined using the specific inhibitor MK-2206, siRNA-mediated knockdown, and FOXO3 overexpression experiments...Anti-apoptosis via the mTOR pathway and antioxidant defense through the FOXO3-Keap1-Nrf2 axis. This study provides comprehensive evidence of apigenin's AKT1-centered mechanism of action in CaOx nephropathy, supporting its potential as a novel therapeutic agent for kidney stone disease."

IO biomarker • Journal • CNS Disorders • Renal Calculi • Renal Disease • BAX • BCL2 • FOXO3 • KEAP1

ADAM17-Driven NKG2D Ligand Shedding Defines a Leukemia-Intrinsic Immune Evasion Program That Predicts Venetoclax Resistance and Reveals MEK and PI3K as Therapeutic Vulnerabilities in AML (SOHO 2026) - "Drug vulnerability mapping identified MEK inhibitors (trametinib, selumetinib), the HDAC inhibitor panobinostat, and PI3K/AKT/mTOR inhibitors (GDC-0941, MK-2206, and INK-128) as selectively active in NK-high AML (all FDR <0.001). An ADAM17-centered NK immune evasion score identifies venetoclax-resistant AML across two independent cohorts and associates with a survival disadvantage equivalent to an 88% increase in hazard per SD of score. This phenotype is consistent with BCL2 independence and engagement of compensatory MAPK and PI3K survival signaling, nominating MEK and PI3K inhibitors as biologically therapeutic alternatives for refractory patients. Prospective biomarker-stratified trials are required before clinical implementation of this scoring approach."

IO biomarker • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Oncology • ADAM17 • BCL2 • HLA-E • NKG2D • SMAD3 • TGFB1 • TIMP3 • ULBP1 • ULBP2

Multi-Omics Integration Identifies CDH3-Driven Malignant Progression and Pathology-Based Risk Stratification in Thymic Epithelial Tumors (IASLC-WCLC 2026) - "Drug-sensitivity analyses prioritized BMS-754807 and MK-2206 as candidate agents, both of which showed antitumor activity in xenograft and patient-derived organoid models. Multi-omic and histopathologic analyses identified CDH3 as a biomarker and functional driver of aggressive disease, associated with poor prognosis, genomic instability, and macrophage/fibroblast-rich microenvironments. Functional and pharmacologic evidence further supported CDH3 as a potentially targetable mediator of aggressive TET biology, with pharmacologic inhibition showing antitumor effects in xenograft and organoid models."

Oncology • Solid Tumor • Thymic Carcinoma • Thymic Epithelial Tumor • Thymus Cancer • CDH3 • CTGF • LRP1 • TGFB1 • VIM

Pathologic complete response (pCR) rates for HR+/HER2- breast cancer by molecular subtype in the I-SPY2 Trial. (ASCO 2022) - P2 | "Investigational agents are given with control weekly paclitaxel x 12, followed by AC x 4...For MK2206, BP Luminal pts were more likely to achieve pCR... Our data suggest that MP2 and BP Basal signatures identify a subset of HR+/HER2- BC more likely to respond to neoadjuvant therapy; and that an immune signature can identify pts more likely to respond to pembrolizumab. These findings will aid in guiding prioritization of targeted agents with the goal to optimize pCR for all pts."

Clinical • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • HER-2

Network pharmacological combined with in vivo and in vitro validation reveals the mechanisms of atrazine-induced Parkinson's disease-related neurotoxicity. (PubMed, Toxicol Appl Pharmacol) - "ATR-triggered microglial activation, proinflammatory cytokine release and PI3K/AKT/JNK phosphorylation were detected in BV2 cells, which were reversed by AKT inhibitor MK2206...Notably, the in vitro (40 μM) and in vivo (25 mg/kg/d) doses used in this study are substantially higher than typical human environmental exposure levels; these findings cannot be directly extrapolated to human health risk assessment. This study provides a candidate intervention strategy for ATR-associated neuronal injury observed in the experimental model."

Journal • Preclinical • CNS Disorders • Inflammation • Movement Disorders • Parkinson's Disease

Integrative docking and molecular dynamics identify potential allosteric modulators of AKT1. (PubMed, J Mol Graph Model) - "The top XP-ranked compounds, compound 1 (docking score: -11.771 kcal/mol), compound 2 (-11.428 kcal/mol), and compound 3 (-11.167 kcal/mol), achieved more favourable XP docking scores at the AKT1 allosteric site (PDB ID: 3O96) than established pan-AKT inhibitors, including MK-2206, miransertib, Bay1125976, and vevorisertib, although MM-GBSA rescoring did not reproduce this ordering. Comprehensive 300-ns all-atom molecular dynamics (MD) analysis, encompassing RMSD and RMSF profiling, principal component analysis, dynamic cross-correlation matrix analysis, free energy landscape evaluation, and protein-ligand contact profiling, consistently demonstrated that compounds 1 and 2 maintain stable, high-affinity interactions with AKT1, exhibiting persistent engagement with the critical allosteric residues Trp80 and Tyr272 throughout the simulation trajectory. Furthermore, both compounds exhibited favourable pharmacokinetic profiles with predicted human oral absorption values over..."

Journal • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • AKT1 • AKT2

PD16, a steroidal saponin, induces apoptosis in colorectal cancer via inhibiting the AKT/GSK3β signaling pathway. (PubMed, Eur J Pharmacol) - "Additionally, combination treatment with the AKT inhibitor MK-2206 enhanced PD16-induced apoptotic effects and further suppressed AKT/GSK3β signaling...In xenograft mouse models, PD16 markedly inhibited CRC tumor growth with concomitant downregulation of the AKT/GSK3β pathway, without major organ toxicity. Collectively, these findings provide the first evidence that PD16 exerts pro-apoptotic effects in CRC cells through the AKT/GSK3β pathway inhibition, thereby confirming it as a valuable novel therapeutic candidate for CRC."

IO biomarker • Journal • Colorectal Cancer • Oncology • Solid Tumor • BCL2 • CASP3 • CASP9

PCSK9 as a Key Gene of Metastasis in Lung Adenocarcinoma: A Multi-omics and Experimental Validation Study. (PubMed, Front Biosci (Landmark Ed)) - "PCSK9 expression is associated with the prognosis and diagnosis of LUAD. This molecule activates the PI3K/AKT signaling pathway, thereby driving invasion, metastasis, and proliferation in LUAD."

Journal • Retrospective data • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • PCSK9

Insulin enhances RAGE ectodomain shedding by inducing Rab14-dependent ADAM10 cell surface trafficking in human aortic endothelial cells. (PubMed, PLoS One) - "Likewise, knockdown of AKT1, AKT2, or AKT3 using siRNA, as well as treatment with the pan-AKT inhibitor MK-2206, inhibited insulin-induced ADAM10 cell surface translocation and RAGE ectodomain shedding...Conversely, Rab14 knockdown blocked insulin-induced ADAM10 cell surface translocation and RAGE ectodomain shedding, thereby abolishing the protective effect of insulin against AGE-BSA-induced ICAM-1 expression. Collectively, these findings demonstrate that insulin promotes Rab14-mediated trafficking of ADAM10 to the cell surface through AKT activation in HAECs, resulting in enhanced RAGE ectodomain shedding."

Journal • ADAM10 • AKT2 • ICAM1

Regulatory role of lncRNA DANCR in osteogenic differentiation of bone marrow mesenchymal stem cells through targeting the miR-19a-3p/PTEN/AKT/mTOR pathway. (PubMed, In Vitro Cell Dev Biol Anim) - "LncRNA DANCR knockdown activated the AKT/mTOR pathway, whereas lncRNA DANCR overexpression or MK-2206 treatment disrupted this activation. Silencing of lncRNA DANCR facilitates BMSC OD by binding to miR-19a-3p and further regulating the PTEN/AKT/mTOR pathway."

Journal • Osteoporosis • Rheumatology • DANCR • MIR19A • RUNX2 • SPP1

Salvianolic acid A promotes angiogenesis after stroke by targeting AKT to alleviate oxidative stress. (PubMed, Brain Res Bull) - "AKT inhibitor MK-2206 counteracted the pro-angiogenic effect of SAA. In conclusion, SAA promotes post-stroke angiogenesis by targeting AKT and activating Nrf2-mediated antioxidant signaling, thereby protecting vascular endothelial function and improving neurological recovery. These findings provide new insights into vascular repair after IS and highlight SAA as a potential therapeutic candidate for stroke recovery via modulating angiogenesis."

Journal • Cardiovascular • CNS Disorders • Ischemic stroke • Thrombosis • Vascular Neurology • ANGPT1 • CLDN5 • OCLN • TJP1

Batri-7 Attenuates Established Inflammation-Associated Colorectal Adenoma via PI3K/AKT Inhibition and BAX-Associated Apoptosis. (PubMed, J Ethnopharmacol) - "BT-7 effectively suppresses progression of established IACA in the inflammatory context by inhibiting the PI3K/AKT signaling pathway and activating BAX-associated apoptosis. These preclinical findings demonstrate that BT-7 exerts therapeutic efficacy against established inflammation-associated colorectal adenoma, providing a mechanistic foundation for its further translational investigation."

Journal • Colorectal Cancer • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammation • Oncology • Solid Tumor

Circulating tumor DNA in neoadjuvant-treated breast cancer reflects response and survival. (PubMed, Ann Oncol) - "Lack of ctDNA clearance was a significant predictor of poor response and metastatic recurrence, while clearance was associated with improved survival even in patients who did not achieve pCR. Personalized monitoring of ctDNA during NAC of high-risk early breast cancer may aid in real-time assessment of treatment response and help fine-tune pCR as a surrogate endpoint of survival."

Clinical • Journal • Breast Cancer • Oncology • Solid Tumor

Osteoclasts' extracellular vesicles induce osteogenesis of human periodontal ligament cells via AKT activation. (PubMed, Arch Oral Biol) - "OC-EVs can induce osteogenesis of PDL cells via RANK-RANKL signaling and AKT activation as parallel contributions."

Journal • TNFRSF11A • TNFRSF11B

Cottonseed Oil Attenuates Traumatic Brain Injury by Inhibiting AKT/GSK-3β-mediated Neuroinflammatory Responses. (PubMed, Mol Neurobiol) - "Mechanistically, the neuroprotective effects of CSO were associated with activation of the AKT/GSK-3β signaling pathway, characterized by enhanced phosphorylation of AKT (Ser473) and inhibitory phosphorylation of GSK-3β (Ser9). Pharmacological inhibition of AKT with MK2206 abolished CSO-induced AKT/GSK-3β pathway activation, reduced cell viability, and restored the elevation of IL-1β and IL-6 levels in vitro, confirming that the anti-neuroinflammatory effects of CSO are mediated at least in part through the AKT/GSK-3β signaling axis. Collectively, these findings demonstrate that CSO exerts significant neuroprotective effects in experimental TBI by preserving neurovascular integrity, attenuating neuroinflammation, and activating the AKT/GSK-3β pathway, highlighting CSO as a promising preventive strategy for TBI."

Journal • Cardiovascular • CNS Disorders • Inflammation • Vascular Neurology • AQP4 • IL1B • IL6

Catalase Defines Radiotherapy Resistance and a Therapeutic Vulnerability in Rhabdomyosarcoma. (PubMed, Int J Mol Sci) - "Furthermore, co-targeting catalase and Akt using sub-toxic doses of 3-ATA and MK-2206 cooperatively enhanced oxidative stress-mediated cytotoxicity in resistant cells. Together, these findings identify catalase as a pivotal driver of adaptive radioresistance and establish dual catalase/Akt targeting as a promising pro-oxidant strategy to overcome radiotherapy resistance in RMS."

Journal • Nasopharyngeal Carcinoma • Oncology • Pediatrics • Rhabdomyosarcoma • Sarcoma • Soft Tissue Sarcoma • Solid Tumor • CAT

In silico analysis of graviola (Annona muricata) acetogenins as modulators of kidney cancer pathways | Poster Board #1406 (ACS-Fall 2026) - "Binding free energies were converted to estimated dissociation constants (Kd) and benchmarked against FDA-approved RCC therapies (sunitinib, axitinib, and pazopanib). An exploratory scaffold modification incorporating structural elements of the allosteric AKT inhibitor MK-2206 improved predicted AKT1 binding to −8.19 kcal/mol under identical docking conditions. These findings suggest that translationally weighted, pathway-focused computational screening can identify structurally adaptable natural product scaffolds with potential relevance in therapy-resistant RCC."

Genito-urinary Cancer • Kidney Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • Von Hippel-Lindau Syndrome • AKT1 • BCL2 • CASP3 • PIK3CA

Deciphering the Potential Mechanism of Cordycepin in Alleviating Ulcerative Colitis via the AKT1 Signaling Pathway: An Integrated Approach Combining Network Pharmacology, Molecular Docking, and Experimental Validation. (PubMed, J Inflamm Res) - "In Caco-2 cells, AKT inhibition with MK2206 attenuated the protective effects on tight junction integrity and mitochondrial function against LPS-induced injury. These findings suggest that prophylactic administration of cordycepin, a promising natural compound, alleviates experimental colitis, potentially through modulation of the PI3K/AKT1 signaling pathway and restoration of epithelial barrier integrity."

Journal • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammation • Inflammatory Bowel Disease • Ulcerative Colitis • AKT1 • RELA • TJP1 • TP53

TGα2β-modified adipose-derived stem cell exosomes regulate collagen synthesis in fibroblasts and enhance chronic ulcerative wound repair through the ILK/AKT signaling pathway. (PubMed, Pak J Pharm Sci) - "ITGα2β-modified ADSC-exos regulate collagen synthesis in fibroblasts and facilitate chronic ulcerative wound healing via the ILK/AKT signaling pathway."

Journal • Inflammation • COL1A1 • COL3A1 • PECAM1

Dental Pulp Stem Cells Transfer Mitochondria via Tunneling Nanotubes to Drive Hypoxic Angiogenesis. (PubMed, J Dent Res) - "Furthermore, inhibition of AKT signaling with MK-2206 abolished the proangiogenic and prosurvival role associated with MT, suggesting a direct regulatory role. Collectively, these findings establish MT as a vital metabolic lifeline that prevents EC collapse and drives DPSC-supported angiogenesis in the hypoxic pulp during the vulnerable window of pulpal restoration, thereby emphasizing MT as a transformative regenerative endodontic target."

Journal

Dioscin Reverses Drug Resistance via AKT/GSK3β-mediated P-gp Degradation and EMT Inhibition. (PubMed, Drug Dev Res) - "Aberrantly activated AKT‑GSK‑3β signaling modulates the expression and degradation of the drug efflux pump P-gp, which expels chemotherapeutic agents, including paclitaxel (PTX), from cancer cells, resulting in chemotherapy failure and drug resistance...Western blotting, Co-IP, and MG132 and MK2206 rescue experiments clarified AKT/GSK3β-dependent P-gp ubiquitin-proteasomal degradation and EMT suppression...In vivo, Dio restrained xenograft tumor growth with negligible systemic toxicity, and intratumoral expression patterns of AKT/GSK3β, P-gp, and EMT-related proteins mirrored in vitro findings. Dio has the potential to be a safe and effective agent for drug-resistant cancer therapy."

Journal • Oncology • Targeted Protein Degradation

Acute AKT signaling increases glucose phosphorylation and contribution to glycogen in hepatocytes. (PubMed, iScience) - "MK-2206 also decreased glucose contribution to glycogen, independent of glycogen breakdown or glycogen synthase phosphorylation. These results demonstrate that AKT acutely regulates glucose contribution to glycogen and upstream precursors, suggesting a transcription-independent mechanism that is proximal to glucose 6-phosphate generation for glycogen synthesis."

Journal

HECW2 suppresses non-small cell lung cancer progression by destabilizing SCNN1A and inactivating AKT/mTOR pathway. (PubMed, Biochem Pharmacol) - "The relationship between SCNN1A and AKT/mTOR pathway was further verified using MK2206 and SC79...HECW2 binds to SCNN1A and promoted SCNN1A ubiquitination with the K48-linked manner and proteasomal degradation. In conclusion, HECW2 inhibited the development of NSCLC via mediating SCNN1A ubiquitination by inactivating the AKT/mTOR pathway and could be a potential target in NSCLC."

Journal • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Targeted Protein Degradation • SCNN1A • UBR5 • WWP2

c-MET Overexpression Drives AKT Activation, and Combined Inhibition Synergistically Enhances Therapeutic Sensitivity in Non-Small-Cell Lung Cancer. (PubMed, Cells) - "Notably, combined inhibition of c-MET (PHA665752) and AKT (MK2206) exhibited strong synergistic effects, significantly enhancing apoptosis and reducing cell viability compared to single-agent treatments. These findings were further validated in vivo, where combination therapy markedly delayed tumor growth without significant toxicity. Collectively, our results highlight c-MET-driven AKT activation as a key oncogenic mechanism and support dual c-MET/AKT targeting as a promising therapeutic strategy for NSCLC."

Journal • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • MET