A 443654 / AbbVie - LARVOL DELTA

Identification of Immune Characteristics of 2 Subtypes of Breast Cancer by Combining Polyamine Metabolism-related Genes to Help With Immunotherapy. (PubMed, J Immunother) - "Cluster 1 exhibited higher sensitivity to (5Z)-7-Oxozeaenol, 5-Fluorouracil, and 681640, while cluster 2 exhibited higher sensitivity to A-443654 and A-770041. We identified 2 clusters of PMRG with significant differences in the immune microenvironment in BC and predicted potential drugs, aiming to find new directions for clinical treatment of BC."

IO biomarker • Journal • Breast Cancer • Oncology • Solid Tumor

Gene expression profiling and pathway analysis in head and neck squamous cell carcinoma: focus on disulfidptosis. (PubMed, Discov Oncol) - "DRGscore effectively predicted survival (P < 0.001), immunotherapy response (anti-PD1/PD-L1 cohorts: P = 0.0099-0.018), and drug sensitivity (A443654 IC50 = 0.12 μM vs. AICAR = 8.3 μM). Mutational profiling identified TP53 and MUC16 as high-risk biomarkers. These findings establish DRGscore as a robust prognostic tool integrating disulfidptosis biology and immune contexture, enabling risk-stratified therapeutic strategies for HNSCC."

IO biomarker • Journal • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • MUC16 • RAC1 • SLC7A11 • TP53

Investigation of mitochondrial DNA methylation-related prognostic biomarkers in hepatocellular carcinoma using The Cancer Genome Atlas (TCGA) database. (PubMed, Transl Cancer Res) - "The chemotherapeutic drug sensitivity analysis revealed significant differences in sensitivity to BI.2536 [a Polo-like kinase 1 (Plk1) inhibitor], A.443654 [a protein kinase B (Akt) 1/2 inhibitor], and ABT.888 [Veliparib, a poly(ADP-ribose) polymerase 1/2 (PARP1/2) inhibitor] between the high- and low-risk groups. It also elucidated the pathogenesis of MTDM-associated HCC. Our findings provide novel insights that could lead to the development of future therapeutic strategies."

Biomarker • Journal • Hepatocellular Cancer • Oncology • Solid Tumor • ADH4 • CD8 • DNASE1L3 • PLK1

The effect of AKT inhibition in α-synuclein-dependent neurodegeneration. (PubMed, Front Mol Neurosci) - "We observed that administration of the AKT inhibitor, A-443654 led to mild improvements in both survival and motor function in flies expressing human α-Syn...The protective effects of AKT reduction appear to operate through the fly ortholog of NF-κB, Relish, suggesting a link between AKT and NF-κB in regulating α-Syn levels. These findings highlight the AKT cascade as a potential therapeutic target for synucleinopathies and provide insights into mechanisms that could be utilized to reduce α-Syn toxicity in PD and related disorders, such as multiple system atrophy."

Journal • CNS Disorders • Movement Disorders • Multiple System Atrophy • Parkinson's Disease • Proteinopathy

5,7-Dihydroxy-4-Methylcoumarin enhances osteogenesis and ameliorates osteoporosis via the AKT1 pathway. (PubMed, Biochem Pharmacol) - "Co-treatment with the AKT1 inhibitor A-443654 abolished the anti-osteoporotic effects of D4M. These findings demonstrate that D4M enhances osteoblast differentiation and mitigates osteoporosis through its interaction with AKT1, suggesting its potential as a therapeutic agent for treating osteoporosis."

Journal • Inflammation • Osteoporosis • Rheumatology

A high-throughput approach to identify BRCA1-downregulating compounds to enhance PARP inhibitor sensitivity. (PubMed, iScience) - "Three compounds, N-acetyl-N-acetoxy chlorobenzenesulfonamide (NANAC), A-443654, and CHIR-124, were validated to reduce BRCA1 protein levels and sensitize breast cancer cells to the toxic effects of olaparib. These results suggest that BRCA1-HiBiT reporter cells hold promise in developing agents to improve the clinical utility of PARPi."

Journal • Breast Cancer • Oncology • Solid Tumor • BRCA1

Identification of a Macrophage marker gene signature to evaluate immune infiltration and therapeutic response in hepatocellular carcinoma. (PubMed, Heliyon) - "Moreover, a low-Macrosig score indicates increased sensitivity to AZD.2281, A.443654, ABT.263, ABT.888, AG.014699 and ATRA, while a high Macrosig score indicates increased sensitivity to AZD6482, AKT inhibitor VIII, AS601245, AZ628, AZD.0530 and AZD6244. A novel scoring system was constructed to guide more effective prognostic evaluation and tailoring therapeutic regimens for HCC patients."

Gene Signature • IO biomarker • Journal • Gastrointestinal Cancer • Hepatocellular Cancer • Oncology • Solid Tumor • LAG3 • PD-1 • TIGIT

AI identifies potent inducers of breast cancer stem cell differentiation based on adversarial learning from gene expression data. (PubMed, Brief Bioinform) - "Experimental validation in MDA-MB-231 and MCF7 cells demonstrated the efficacy of five out of six tested molecules among those scored highest by the model. In particular, the efficacy of triptolide, OTS-167, quinacrine, granisetron and A-443654 offer a potential avenue for targeted therapies against breast CSCs."

Cancer stem • Journal • Breast Cancer • Oncology • Solid Tumor

A programmed cell death-related signature in predicting cisplatin reactivity in ovarian cancer (SGO 2024) - "In addition, patients with low-risk scores had higher immune-infiltrating cells and enhanced expression of checkpoints, PD-L1, IDO-1 and LAG3, and were more sensitive to A.443654, GDC.0449, paclitaxel, gefitinib and cisplatin. Our model could precisely predict the prognosis, immune status and drug sensitivity of OC patients. Patients with high model score are more resistant to cisplatin than low score ones."

IO biomarker • Colorectal Cancer • Oncology • Ovarian Cancer • Solid Tumor • CD3E • CEBPB • IDO1 • IGF2BP1 • LAG3 • PD-L1 • PPP1R15A • RB1 • TMB • ZBP1

Exploring the Potential of Akt Modulator A-443654 as a Therapeutic Approach for Parkinson's Disease: Insights from Drosophila melanogaster Models (Neuroscience 2023) - "Our findings provide evidence that the Akt modulator A-443654 may hold potential as a treatment for PD, as demonstrated in the enhanced longevity in the fly models subjected to α-synuclein toxicity. These results serve as a pilot study for further exploration in mouse models of PD, paving the way for future investigation of a promising direction of therapeutic intervention for PD."

CNS Disorders • Parkinson's Disease • Psychiatry

Constructing a prognostic model for head and neck squamous cell carcinoma based on glucose metabolism related genes. (PubMed, Front Endocrinol (Lausanne)) - "GDSC database analysis identified 53 drugs with remarkable differences between the groups, including A.443654 and AG.014699. Our study highlights the significant association of five prognosis-related genes (MTHFD2, CDKN2A, TPM2, MPZ, and DNMT1) with HNSC. These findings provide further evidence of the crucial role of GMRGs in HNSC."

Journal • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • CDKN2A • DNMT1 • MTHFD2 • TPM2

A novel prognostic N-methylguanosine-related long non-coding RNA signature in clear cell renal cell carcinoma. (PubMed, Sci Rep) - "High-risk group of patients was more susceptible to A.443654, A.770041, ABT.888, AMG.706, and AZ628. Quantitative real-time polymerase chain reaction (qRT-PCR) exhibited that the expression levels of LINC01507, AC093278.2 were very high in all five ccRCC cell lines, AC084876.1 was upregulated in all ccRCC cell lines except 786-O, and the levels of AL118508.1 and DUXAP8 were upregulated in the Caki-1 cell line. This risk model may be promising for the clinical prediction of prognosis and immunotherapeutic responses in patients with ccRCC."

IO biomarker • Journal • Tumor mutational burden • Clear Cell Renal Cell Carcinoma • Genito-urinary Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • DUXAP8 • TMB

Predicting response of immunotherapy and targeted therapy and prognosis characteristics for renal clear cell carcinoma based on m1A methylation regulators. (PubMed, Sci Rep) - ""pRRophetic" package screened five potential small molecule drugs (A.443654, A.770041, ABT.888, AG.014699, AMG.706). Finally, polymerase chain reaction (PCR) showed the expression of YTHN6-Methyladenosine RNA Binding Protein 1[YTHDF1], TRNA Methyltransferase 61B [TRMT61B], TRNA Methyltransferase 10C [TRMT10C] and AlkB Homolog 1[ALKBH1] in ccRCC cell lines. To sum up, the prognosis risk model we created not only has good predictive value, but also can provide guidance for accurately predicting the prognosis of ccRCC."

IO biomarker • Journal • Clear Cell Renal Cell Carcinoma • Colorectal Cancer • Gastrointestinal Cancer • Genito-urinary Cancer • Oncology • Rectal Cancer • Renal Cell Carcinoma • Solid Tumor • EGFR • ER • YTHDF1

Identification of Macrophage Associated Gene Landscape to Evaluate Immune Infiltration and Therapeutic Response in Hepatocellular Carcinoma (APPLE 2023) - "A novel scoring system based on macrophage subclusters was constructed, thereby guiding more effective prognostic evaluation and tailored potential drug agents strategies of HCC patients."

IO biomarker • Gastrointestinal Cancer • Hepatocellular Cancer • Immune Modulation • Oncology • Solid Tumor • LAG3 • PD-1 • TIGIT

Eurycomanone stimulates bone mineralization in zebrafish larvae and promotes osteogenic differentiation of mesenchymal stem cells by upregulating AKT/GSK-3β/β-catenin signaling. (PubMed, J Orthop Translat) - "Eventually in vitro, the effect of EN on cell viability, osteogenesis activities were investigated in human bone marrow mesenchymal stem cells (hMSCs) and C3H10 cells, and the molecular mechanisms by which applying AKT inhibitor A-443654 in hMSCs...Meanwhile, exposure of EN remarkably alleviated the inhibition of bone formation induced by dexamethasone (Dex), prominently improved the mineralization, up-regulated osteoblast-specific genes and down-regulated osteoclast-related genes (CTSK, RANKL, NFATc1, TRAF6) in Dex-treated bone loss zebrafish larvae...Altogether, our findings indicate that EN possesses remarkable effect on bone formation via activating AKT/GSK-3β/β-catenin signaling pathway in most tested concentrations. This study demonstrates EN is a new effective monomer in promoting bone formation, which may be a promising anabolic agent for osteoporosis (OP) treatment."

Journal • Osteoporosis • Rheumatology • CTSK • GSK3B • NFATC1 • RUNX2 • TRAF6

A risk model constructed using 14 N-methyladenosine-related lncRNAs as a new prognostic marker that correlates with the immunomodulatory effect and drug sensitivity in colorectal cancer. (PubMed, J Gastrointest Oncol) - "Finally, we identified 12 drugs, including A-443654 and sorafenib, with lower half maximal inhibitory concentration (IC) values in the high-risk group. Conversely, 21 drugs, including gemcitabine and rapamycin, had lower IC values in the low-risk group. We constructed a risk model based on 14 mA-related lncRNAs that could predict the prognosis of patients with CRC and provided additional therapeutic ideas for their treatment. These findings may additionally serve as a foundation for further studies on regulating CRC via mA-related lncRNAs."

Biomarker • Immunomodulating • IO biomarker • Journal • Tumor mutational burden • Colorectal Cancer • Gastrointestinal Cancer • Gastrointestinal Disorder • Immune Modulation • Oncology • Solid Tumor • TMB

Bioinformatics prediction and experimental verification identify cuproptosis-related lncRNA as prognosis biomarkers of hepatocellular carcinoma. (PubMed, Biochem Biophys Rep) - "Besides, we screened for two chemical drugs (A-443654 and Pyrimethamine) with the greatest value for high-risk HCC patients. And proliferative, migratory and invasion abilities of HCC cell were restrained via silencing CAlncRNAs expression in vitro. In summary, we built a CAlncRNAs-based risk score model, which can be a candidate for HCC patients prognostic prediction and offer some useful information for immunotherapies."

Biomarker • IO biomarker • Journal • Gastrointestinal Cancer • Hepatocellular Cancer • Oncology • Solid Tumor • FOXD2-AS1 • TMB

Metabolomic analysis of vascular cognitive impairment due to hepatocellular carcinoma. (PubMed, Front Neurol) - "The drug screening revealed the potential clinical efficacy of A-443654, A-770041, AP-24534, BI-2536, BMS- 509744, CGP-60474, and CGP-082996. HCC-associated metabolic DEGs may influence the development of VCI in HCC patients."

Journal • Alzheimer's Disease • Cognitive Disorders • Gastrointestinal Cancer • Hepatocellular Cancer • Oncology • Solid Tumor • CCL2 • NNMT • NR1I2 • PHGDH • PON1 • SOCS3

System analysis based on the pyroptosis-related genes identifies GSDMC as a novel therapy target for pancreatic adenocarcinoma. (PubMed, J Transl Med) - "In this study, we developed a pyroptosis-related prognostic model based on IL18, CASP4, NLRP1, NLRP2, and GSDMC , which may be helpful for clinicians to make clinical decisions for PAAD patients and provide valuable insights for individualized treatment. Our result suggest that GSDMC may promote the proliferation and migration of PAAD cell lines. These findings may provide new insights into the roles of pyroptosis-related genes in PAAD, and offer  new therapeutic targets for the treatment of PAAD."

Journal • Gastrointestinal Cancer • Hepatology • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Solid Tumor • CASP4 • IL18 • NLRP1

Integrative pharmacogenomics revealed three subtypes with different immune landscapes and specific therapeutic responses in lung adenocarcinoma. (PubMed, Comput Struct Biotechnol J) - "Finally, our study provided subtype-guided personalized treatment strategies: Immune checkpoint blockers (ICBs), doxorubicin, tipifarnib, AZ628, and AZD6244 were for S-Ⅰ; Cisplatin, camptothecin, roscovitine, and A.443654 were for S-Ⅱ; Docetaxel, paclitaxel, vinorelbine, and BIBW2992 were for S-III. We provided a novel molecular classification strategy and revealed three pharmacogenomics-based subtypes for LUAD patients, which uncovered potential subtype-related and patient-specific therapeutic strategies."

Biomarker • Journal • Immune Modulation • Inflammation • Inflammatory Arthritis • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Machine Learning Screens Potential Drugs Targeting a Prognostic Gene Signature Associated With Proliferation in Hepatocellular Carcinoma. (PubMed, Front Genet) - "Prediction of immunotherapy suggetsted the IC50s of immune checkpoint inhibitors including A-443654, ABT-888, AG-014699, ATRA, AUY-922, and AZ-628 in the high-risk group were lower than those in the low-risk group, while the IC50s of AMG-706, A-770041, AICAR, AKT inhibitor VIII, Axitinib, and AZD-0530 in the high-risk group were higher than those in the low-risk group. Drug sensitivity analysis indicated that FARSB was positively correlated with Hydroxyurea, Vorinostat, Nelarabine, and Lomustine, while negatively correlated with JNJ-42756493. DHX37 was positively correlated with Raltitrexed, Cytarabine, Cisplatin, Tiotepa, and Triethylene Melamine. YARS was positively correlated with Axitinib, Fluphenazine and Megestrol acetate. NOP58 was positively correlated with Vorinostat and 6-thioguanine... The five-gene signature associated with proliferation can be used for survival prediction and risk stratification for HCC patients. Potential drugs targeting this gene signature..."

IO biomarker • Journal • Gastrointestinal Cancer • Hepatocellular Cancer • Immune Modulation • Inflammation • Oncology • Solid Tumor

Prognostic Value of Drug Targets Predicted Using Deep Bioinformatic Analysis of m6A-Associated lncRNA-Based Pancreatic Cancer Model Characteristics and Its Tumour Microenvironment. (PubMed, Front Genet) - "Eight sensitive drugs were screened: ABT.888, ATRA, AP.24534, AG.014699, ABT.263, axitinib, A.443654, and A.770041. We screened m6A-related lncRNAs using bioinformatics, constructed a prognosis-related model, explored TMB and immune function differences in pancreatic cancer, and identified potential therapeutic agents, providing a foundation for further studies of pancreatic cancer diagnosis and treatment."

Journal • Preclinical • Tumor microenvironment • Gastrointestinal Cancer • Hepatology • Immune Modulation • Immunology • Inflammation • Oncology • Pancreatic Cancer • Solid Tumor • KRAS • SMAD4 • TMB • TP53

Identification of Fatty Acid Metabolism-Related lncRNAs as Biomarkers for Clinical Prognosis and Immunotherapy Response in Patients With Lung Adenocarcinoma. (PubMed, Front Genet) - "We found that A.443654, AUY922, AZ628, A.770041, AZD.0530, AMG.706, and AG.014699 were more effective in high-risk patients. We constructed a 7-lncRNA prognostic model to predict the OS of patients with LUAD. In addition, the predictive nomogram model based on our established seven fatty acid metabolism-related lncRNA signatures provides better clinical value than that of the traditional TNM staging system in predicting the prognosis of patients with LUAD and presents new insights for personalized treatment."

Biomarker • IO biomarker • Journal • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

The Role of m5C-Related lncRNAs in Predicting Overall Prognosis and Regulating the Lower Grade Glioma Microenvironment. (PubMed, Front Oncol) - "The high-risk group was more sensitive to anti-CTLA4 therapy and to compounds including Temozolomide, Bleomycin, Cisplatin, Cyclopamine, A.443654 (Akt inhibitor), AZD6482 (PI3K inhibitor), GDC0941(PI3K inhibitor), and metformin. We present for the first time a m5C-related lncRNA signature for lower grade glioma patient prognosis and therapy response prediction with validated performance, providing a promising target for future research."

IO biomarker • Journal • Brain Cancer • Glioma • Oncology • Solid Tumor

The AKT modulator A-443654 reduces α-synuclein expression and normalizes ER stress and autophagy. (PubMed, J Biol Chem) - "A-443654 also decreased the expression of DCLK1, an inhibitor of α-synuclein lysosomal degradation. Our study identifies A-443654 and AKT inhibition as a potential strategy for reducing SNCA expression and preventing PD pathology."

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