GDC 0879 / Roche - LARVOL DELTA

Profiling with senescence-associated secretory phenotype score identifies GDC-0879 as a small molecule sensitizing glioblastoma to anti-PD1. (PubMed, Cell Death Dis) - "Then, we validate this score with functional assays and transcriptomic profiling of Doxorubicin-induced senescence GBM cells. Together, we provide a SASP evaluation approach in glioma, and use it to highlight the critical role of SASP in GBM progression and demonstrate GDC-0879 as a small molecule impairing GBM tumorigenicity and improving their response to anti-PD1. Created by Figdraw ( www.figdraw.com )."

Journal • Brain Cancer • Glioblastoma • Glioma • Oncology • Solid Tumor

A novel cell-based assay for the high-throughput screening of epithelial-mesenchymal transition inhibitors: Identification of approved and investigational drugs that inhibit epithelial-mesenchymal transition. (PubMed, Lung Cancer) - "We systematically screened approved, investigational, and druggable compounds with inhibitory effects using a reporter assay, and identified candidate drugs for EMT inhibition."

Journal • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CDH1 • TGFB1 • VIM

A novel cell-based assay for the high-throughput screening of epithelial–mesenchymal transition inhibitors: Identification of approved and investigational drugs that inhibit epithelial–mesenchymal transition (Lung Cancer) - "We generated a luciferase reporter cell line using A549 human lung cancer cells and E-cadherin or vimentin as EMT markers....Values obtained by the assay were adjusted for the number of viable cells and scored by determining the difference between mean values of the positive and negative control groups. Four compounds were identified as novel candidate drugs. Among those, one (avagacestat) and two compounds (GDC-0879 and levothyroxine) improved the expression of E-cadherin and vimentin, respectively, in epithelial cells. GDC-0879 and levothyroxine also significantly inhibited the invasive capacity of cells."

Preclinical • Lung Cancer • Non Small Cell Lung Cancer • Oncology

Predicting the Prognosis of Esophageal Adenocarcinoma by a Pyroptosis-Related Gene Signature. (PubMed, Front Pharmacol) - "Several inhibitors including GDC-0879 and PD-0325901 are promising in reversing the altered differentially expressed genes in high-risk patients. Our findings provide insights into the involvement of pyroptosis in EAC progression and are promising in the risk assessment as well as the prognosis for EAC patients in clinical practice."

Journal • Esophageal Adenocarcinoma • Esophageal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor

MEK1/2 is a bottleneck that induces cancer stem cells to activate the PI3K/AKT pathway. (PubMed, Biochem Biophys Res Commun) - "The miPS cells were cultured for one week in the presence of the conditioned medium (CM) of Lewis lung carcinoma (LLC) cells and AZD-6244, PD0325901, a pan-MEK inhibitor, or GDC-0879, a B-Raf inhibitor. Moreover, converted cells gained migration and invasion abilities assessed by in vitro assays. Therefore, the inhibition of MEK1/2 was found to be critical for the conversion of normal stem cells into CSCs in the tumor-inducing microenvironment."

Cancer stem cells • Journal • Immunology • Inflammation • Lung Cancer • Oncology • Solid Tumor • BRAF • CD133 • CD24 • CD44 • MAP2K1

Targeting a Braf/Mapk pathway rescues podocyte lipid peroxidation in CoQ deficiency kidney disease. (PubMed, J Clin Invest) - "Treatment with GDC-0879, a Braf/Mapk-targeting compound ameliorated kidney disease in Pdss2kd/kd mice...We demonstrate broader human disease relevance by uncovering patterns of GPX4 and Braf/Mapk pathway gene expression in tissue from patients with kidney diseases. Our studies reveal ETC-independent roles for CoQ in podocytes and point to Braf/Mapk as a candidate pathway for the treatment of kidney diseases."

Journal • Chronic Kidney Disease • Glomerulonephritis • Nephrology • Renal Disease

[VIRTUAL] GDC-0879 Rescues Lipid Peroxidation and Podocyte Dysfunction in Coenzyme Q-Deficient Kidney Disease (KIDNEY WEEK 2020) - "Our studies reveal ETC-independent roles for CoQ in podocyte injury and point to Braf/Mapk as a conserved, podocyte-specific pathway for the treatment of kidney diseases. Funding: NIDDK Support"

Glomerulonephritis • Nephrology • Renal Disease • BRAF • Pdss2

mTOR inhibitor everolimus reduces invasiveness of melanoma cells. (PubMed, Hum Cell) - "The object of this study is recognition of the possible role of mTOR kinase inhibitors-everolimus single and in combination with selected downstream protein kinases inhibitors: LY294002 (PI3 K), U0126 (ERK1/2), GDC-0879 (B-RAF), AS-703026 (MEK), MK-2206 (AKT), PLX-4032 (B-RRAF) in cell invasion in malignant melanoma. Slightly less profound reduction of invasiveness was obtained for the combinations of an mTOR inhibitor-everolimus with ERK1/2 inhibitor-U126 or MEK inhibitor-AS-703026 and in the case of MMPs activity decrease for PI3 K inhibitor-LY294002 and AKT inhibitor-MK-2206. The simultaneous use of everolimus or another new generation rapalog with selected inhibitors of crucial signaling kinases seems to be a promising concept in cancer treatment."

Journal • Melanoma • Oncology • Solid Tumor