TG 100-115 / Sanofi - LARVOL DELTA

Integrated single-cell and bulk RNA sequencing reveals prognostic and immunotherapy-associated myofibroblastic cancer-associated fibroblast subtypes in head and neck squamous cell carcinoma. (PubMed, Transl Cancer Res) - "Additionally, a higher myCAF score was related to the higher half-maximal inhibitory concentration (IC50) values of D-4476, GW-583340, spautin-1, and VER-155008, and the lower IC50 values of JTE-607, TG100-115, ML320, and TGX-221. This study, which was based on single-cell and bulk RNA-seq analyses, showed the plasticity and metabolic heterogeneity of CAFs in HNSCC. Our findings may contribute to understandings of the immunotherapy response in HNSCC."

Journal • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • CAFs

Targeting PI3K-gamma in myeloid driven tumour immune suppression: a systematic review and meta-analysis of the preclinical literature. (PubMed, Cancer Immunol Immunother) - "The predominant PI3Kγ inhibitors were IPI-549 and TG100-115, demonstrating favourable specificity for the gamma isoform. The combination of PI3Kγ inhibition with other therapeutic modalities demonstrated enhanced antitumour effects, suggesting a synergistic approach to overcome immune suppression. These findings support the potential of PI3Kγ-targeted therapies, particularly in combination regimens, as a promising avenue for future clinical exploration in diverse solid tumour types."

Clinical • Journal • Preclinical • Retrospective data • Review • Gastric Cancer • Head and Neck Cancer • Oncology • Oral Cancer • Solid Tumor • PIK3CG

Identification of the circRNA-miRNA-mRNA regulatory network in osteoarthritis using bioinformatics analysis. (PubMed, Front Genet) - "Finally, three chemicals (noscapine, diazepam, and TG100-115) based on CMap analysis and two drugs (collagenase Clostridium histolyticum and ocriplasmin) based on DGIdb were discovered as potential treatment options for OA. This study presents novel perspectives on the pathogenesis and treatment of OA based on circRNA-related competitive endogenous RNA regulatory networks."

Journal • Immunology • Osteoarthritis • Pain • Rheumatology • COL1A1 • COL5A1 • COL6A3 • MIR1207 • SERPINH1

[6]-Gingerol induces Caspase-Dependent Apoptosis in Bladder Cancer cells via MAPK and ROS Signaling. (PubMed, Int J Med Sci) - "Further, [6]-GIN also increased the intracellular reactive oxygen species (ROS) levels and TG100-115 or tranilast increased [6]-GIN‑induced cell death. These results suggest that [6]-GIN induced apoptosis in the bladder cancer cell line 5637 and therefore has the potential to be used in the development of new drugs for bladder cancer treatment."

Journal • Bladder Cancer • Genito-urinary Cancer • Lymphoma • Oncology • Solid Tumor • Urothelial Cancer • BAX • BIRC5 • CASP3 • CASP9

TRPM7 Kinase Is Essential for Neutrophil Recruitment and Function via Regulation of Akt/mTOR Signaling. (PubMed, Front Immunol) - "Using a recently identified TRPM7 kinase inhibitor, TG100-115, as well as murine neutrophils with genetic ablation of the kinase activity, we confirm the importance of both TRPM7 channel and kinase function in murine neutrophil transmigration and unravel that TRPM7 kinase affects Akt1/mTOR signaling thereby regulating neutrophil transmigration and effector function. Hence, TRPM7 represents an interesting potential target to treat unwanted excessive neutrophil invasion."

Journal • Immunology • Inflammation • Inflammatory Arthritis • Rheumatoid Arthritis • Rheumatology • AKT1 • CXCL8 • TRPM7

[VIRTUAL] Pancreatic cancer therapy based on combination of DNA vaccination and PI3Kgamma inhibition (SITC 2020) - "Conclusions Treatment with ENO1 plus TG100-115 is able to reduce tumor size in pancreas, increase immune cell infiltration and modulate stroma cell compartment, making the therapy a suitable approach for PDA treatment. Ethics Approval All animal experiments were approved by the University of Torino, Italian Ministry of Health and performed in accordance with EU laws in the animal facility of the Molecular Biotechnology Center (MBC)."

Gastrointestinal Cancer • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • CD31 • CD8 • FOXP3 • GZMB • PIK3CG

[VIRTUAL] Pancreatic cancer therapy based on combination of DNA vaccination and PI3Kgamma inhibition (SITC 2020) - "Conclusions Treatment with ENO1 plus TG100-115 is able to reduce tumor size in pancreas, increase immune cell infiltration and modulate stroma cell compartment, making the therapy a suitable approach for PDA treatment. Ethics Approval All animal experiments were approved by the University of Torino, Italian Ministry of Health and performed in accordance with EU laws in the animal facility of the Molecular Biotechnology Center (MBC)."

Gastrointestinal Cancer • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • CD31 • CD8 • FOXP3 • GZMB • PIK3CG

Suppression of TRPM7 enhances TRAIL-induced apoptosis in triple-negative breast cancer cells. (PubMed, J Cell Physiol) - "Furthermore, we showed that the synergistic interaction might be associated with TRPM7 channel activities using combination treatments of TRAIL and TRPM7 inhibitors (NS8593 as a TRPM7 channel inhibitor and TG100-115 as a TRPM7 kinase inhibitor). We reveal that downregulation of cellular FLICE-inhibitory protein via inhibition of Ca influx might be involved in the synergistic interaction. Our study would provide both a new role of TRPM7 in TNBC cell apoptosis and a potential combinatorial therapeutic strategy using TRPM7 inhibitors with TRAIL in the treatment of TNBC."

Journal • Breast Cancer • Genito-urinary Cancer • Prostate Cancer • Solid Tumor • Triple Negative Breast Cancer • TNFA • TRPM7

IL11 SECRETION BY GLIOBLASTOMA ASSOCIATED MICROGLIA DEFINE A STAT3-MYC SIGNALING AXIS THAT IS SUPPRESSED IN “EXCEPTIONAL RESPONDERS” (SNO 2017) - "...Co-culturing of freshly isolated murine microglia derived from GL261 glioblastoma enhanced glioblastoma tumorigenicity and resistance to temozolomide (TMZ), the standard-of-care therapy...Supporting our hypothesis, treatment with a PI3Kg inhibitor, TG100-115, suppressed glioblastoma tumorigenicity in vivo by reduced microglia density and IL11 release...In contrast, ectopic IL11 expression or microglia induce the expression of this signature. In aggregate, our study suggests microglia-glioblastoma interaction as a determinant of clinical response and translational potential for therapies targeting microglia-mediated inflammation"

Oncology • Solid Tumor

Sorafenib-loaded hydroxyethyl starch-TG100-115 micelles for the treatment of liver cancer based on synergistic treatment. (PubMed, Drug Deliv) - "Additionally, micelles demonstrated higher levels of antitumor efficiency and better tolerance against nude mouse with Hep-3B cell than the free drug solutions. These findings reveal that HES-TG100-115-CDM-PEG micelles are a promising drug delivery system in clinical comprehensive therapy of liver cancer."

Journal