CZC24832 / GSK - LARVOL DELTA

Unveiled reactivity of masked diformylmethane with enamines forming resonance-assisted hydrogen bonding leads to di-meta-substituted pyridines. (PubMed, Commun Chem) - "Successful development of the designed methodology linked to wide applications-core remodeling of natural products, drug-natural product conjugation, late-stage functionalization of drug molecules, and synthesis of the regioisomeric CZC24832. Furthermore, we discovered anti-inflammatory agents through the functional evaluation of synthesized bi-heteroaryl analogs, signifying the utility of this methodology."

Journal

The cell death-related genes machine learning model for precise therapy and clinical drug selection in hepatocellular carcinoma. (PubMed, J Cell Mol Med) - "Moreover, our investigation has shown that AZD2014, SB505124, LJI308 and OSI-207 show a greater efficacy in patients in the low-risk category. Conversely, for the high-risk group patients, PD173074, ZM447439 and CZC24832 exhibit a stronger response...This innovative model provides a novel approach for forecasting prognosis and assessing drug sensitivity in HCC patients, driving a more personalized and efficacious treatment paradigm, elevating clinical outcomes. Nonetheless, additional research endeavours are required to confirm the model's precision and assess its potential to inform clinical decision-making for HCC patients."

Journal • Machine learning • Tumor mutational burden • Gastrointestinal Cancer • Hepatocellular Cancer • Oncology • Solid Tumor • TMB

Inhibition of Phosphoinositide 3-Kinase Gamma protects endothelial cells via the Akt signaling pathway in sepsis-induced acute kidney injury. (PubMed, Kidney Blood Press Res) - "In this study, endothelial cell dysfunction plays an important role in sepsis-induced AKI, and the inhibition of PI3Kγ alleviates endothelial cell injury in sepsis-induced AKI through the PI3Kγ/Akt pathway, providing novel targets for treating sepsis and related kidney injury."

Journal • Acute Kidney Injury • Infectious Disease • Nephrology • Renal Disease • Septic Shock • PIK3CG

Time Series Transcriptomic Analysis by RNA Sequencing Reveals a Key Role of PI3K in Sepsis-Induced Myocardial Injury in Mice. (PubMed, Front Physiol) - "Further, blocking PI3Kγ by the specific inhibitor CZC24832 significantly protected against sepsis-induced cardiac impairment. The present study uncovers the gene expression signatures of CLP-induced myocardial injury and sheds light on the role of Pik3r5 in septic cardiomyopathy."

Journal • Preclinical • Cardiomyopathy • Cardiovascular • Infectious Disease • Inflammation • Septic Shock • PIK3CG • PIK3R1

Combined Treatment with PI3K Inhibitors BYL-719 and CAL-101 Is a Promising Antiproliferative Strategy in Human Rhabdomyosarcoma Cells. (PubMed, Molecules) - "In the study reported here, a panel of five compounds targeting the catalytic subunits of the four class I PI3K isoforms (p110α, BYL-719 inhibitor; p110β, TGX-221 inhibitor; p110γ, CZC24832; p110δ, CAL-101 inhibitor) and the dual p110α/p110δ, AZD8835 inhibitor, were tested on the RMS cell lines RD, A204, and SJCRH30. When combined with CAL-101, BYL-719 decreased cell viability and induced apoptosis in a synergistic manner, equaling or surpassing results achieved with AZD8835. In conclusion, our findings indicate that BYL-719, either alone or in combination with the p110δ inhibitor, CAL-101, could represent an efficient treatment for human rhabdomyosarcoma presenting with aberrant upregulation of the PI3K signaling pathway."

Journal • Oncology • Pediatrics • Rhabdomyosarcoma • Sarcoma • Soft Tissue Sarcoma • Solid Tumor • PIK3CA • PIK3CG

PROGNOSTIC RELEVANCE AND ANTITUMOR OR IMMUNITY OF NSD3 OVEREXPRESSION IN THE BREAST CANCER (GBCC 2022) - "WHSC1L1 overexpression could play potential roles in the progression of breast cancer, and targeting WHSC1L1 could be a potential strategy for the treatment of breast cancer."

IO biomarker • Breast Cancer • Oncology • Solid Tumor • CD8 • NSD3