TAK-715 / Takeda, BridgeBio - LARVOL DELTA

The link between osteoporosis and frozen shoulder: exploring the therapeutic effect of TAK715 on reversing fibrosis and protecting against osteoporosis via the p38 MAPK signaling pathway. (PubMed, BMC Musculoskelet Disord) - "The frozen shoulder with osteoporosis may exhibit more severe symptoms, and TAK715 is effective in protecting fibrosis and osteoporosis both in vitro and vivo. The therapy to correct FS and OP simultaneously by TAK715 provides novel approach in FS treatment and study."

Journal • Fibrosis • Immunology • Osteoporosis • Rheumatology

Comprehensive Analysis and Experimental Validation of TLL2 as a Potential New Prognostic Biomarker Associated with Immune Infiltration in Lung Adenocarcinoma. (PubMed, Recent Pat Anticancer Drug Discov) - "For patients with LUAD, TLL2 may serve as an immunotherapeutic target and a useful prognosis biomarker."

Biomarker • IO biomarker • Journal • Asthma • Immunology • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pulmonary Disease • Respiratory Diseases • Solid Tumor • Transplant Rejection

Novel anti-cancer effect of 2-arachidonoylglycerol via processing body formation in HCA-7 human colon cancer cells. (PubMed, Prostaglandins Other Lipid Mediat) - "These effects were restored by TAK-715, a specific inhibitor of p38 MAPK...Recently, the cardiovascular risks of NSAIDs were reported by the Food and Drug Administration in the United States. Therefore, elucidation of the effect of 2-AG is expected to contribute to the development of an alternative and novel therapeutic option that would have no or fewer risks regarding cardiovascular events."

Journal • Cardiovascular • Colon Cancer • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • PTGS2

A combination of cuproptosis and lncRNAs predicts the prognosis and tumor immune microenvironment in cervical cancer. (PubMed, Discov Oncol) - "In conclusion, we constructed five cuprotosis-related lncRNA prognostic models, which may be new tumor therapeutic targets for the prevention and treatment of cervical cancer."

Journal • Tumor mutational burden • Cervical Cancer • Oncology • Solid Tumor • Targeted Protein Degradation • TMB

Identification of a cancer-associated fibroblast classifier for predicting prognosis and therapeutic response in lung squamous cell carcinoma. (PubMed, Medicine (Baltimore)) - "In silico drug screening identified 6 effective compounds for high-risk CAFs-related LUSC: TAK-715, GW 441756, OSU-03012, MP470, FH535, and KIN001-266. Additionally, search tool for interaction of chemicals database highlighted PI3K-Akt signaling as a potential target pathway for high-risk CAFs-related LUSC. Overall, our findings provide a molecular classifier for high-risk CAFs-related LUSC and suggest that treatment with PI3K-Akt signaling inhibitors could benefit these patients."

IO biomarker • Journal • Non Small Cell Lung Cancer • Oncology • Squamous Cell Carcinoma • CAFs • KLF10 • PDGFA • SERPINE1 • SMAD7

The signature of immune-subtype specific driving transcription factors suggest potential drugs for refractory glioblastoma. (PubMed, Am J Cancer Res) - "We also found that obatoclax mesylate, NPK76-II-72-1, gemcitabine, TAK-715 are potential drugs for the treatment of refractory GBM based on drug sensitivity models of different immune subtypes. Therefore, we demonstrated that the immune subtypes of GBM have independent prognostic efficacy and can be used as clinical guidance for predicting the progression of GBM and drug sensitivity. Most importantly, this study is expected to provide a pathway for the development of effective drugs for treatment of refractory GBM."

Journal • Brain Cancer • CNS Tumor • Glioblastoma • Oncology • Solid Tumor • EGFR • MGMT

TAK-715 alleviated IL-1β-induced apoptosis and ECM degradation in nucleus pulposus cells and attenuated intervertebral disc degeneration ex vivo and in vivo. (PubMed, Arthritis Res Ther) - "In a rat tail model, TAK-715 ameliorates puncture-induced disc degeneration based on MRI and histopathology evaluations. TAK-715 attenuated intervertebral disc degeneration in vitro and in vivo, suggesting that it might be an effective treatment for IDD."

Journal • Preclinical • Inflammation • HMGB1 • IL1B • MMP3 • MMP9

Suppression of Lipid Accumulation in the Differentiation of 3T3-L1 Preadipocytes and Human Adipose Stem Cells into Adipocytes by TAK-715, a Specific Inhibitor of p38 MAPK. (PubMed, Life (Basel)) - "Of importance, TAK-715 also markedly impeded the phosphorylation of p38 MAPK and suppressed lipid accumulation during the adipocyte differentiation of human adipose stem cells (hASCs). Concisely, this is the first report that TAK-715 (10 μM) has potent anti-adipogenic effects on the adipogenesis process of 3T3-L1 cells and hASCs through the regulation of the expression and phosphorylation of p38 MAPK, C/EBP-α, PPAR-γ, STAT-3, FAS, and perilipin A."

Journal • Genetic Disorders • Obesity • ATF2 • FASN • PLIN2 • PPARG • STAT3

Comprehensive analysis of cuproptosis-related lncRNAs in the prognosis and therapy response of patients with bladder cancer. (PubMed, Ann Transl Med) - "The sensitivity of multiple antitumor drugs was negatively related to risk score, including AR-42, AS605240, FK866, TAK-715, and tubastatin A, while the sensitivity of some antitumor drugs, such as AMG-706, BX-795, and RO-3306, were positively correlated with risk score. Our study established and verified a novel clinical risk signature with cuproptosis-related lncRNAs that may predict therapy response and prognosis with robust and stable accuracy in patients with BLCA and enhance the personalized management of this patient population."

IO biomarker • Journal • Tumor mutational burden • Bladder Cancer • Genito-urinary Cancer • Immune Modulation • Inflammation • Oncology • Solid Tumor • Urothelial Cancer • TMB

Plasma-derived exosomes in chronic spontaneous urticaria induce the production of mediators by human mast cells. (PubMed, J Invest Dermatol) - "TLR-2, TLR-4, and MAPK inhibitors (CC-401, TAK-715, and SCH772984, respectively) reduced EXs-CSU-Stimulated production of inflammatory mediators in HMC-1 cells. Additionally, EXs-CSU-R had more powerful mast cell-activating and histamine-release abilities. Thus, these exosomes may be involved in the pathogenesis of CSU with antihistamine resistance."

IO biomarker • Journal • Chronic Spontaneous Urticaria • Dermatology • Urticaria • TLR4 • TPSAB1

Perturbation of p38α MAPK as a Novel Strategy to Effectively Sensitize Chronic Myeloid Leukemia Cells to Therapeutic BCR-ABL Inhibitors. (PubMed, Int J Mol Sci) - "A highly specific p38α inhibitor, TAK715, also significantly enhanced the imatinib- and dasatinib-mediated therapeutic efficacy, supporting the feasibility of p38α deficiency in future clinic application. Taken together, our results demonstrated that p38α is a promising target for combined therapy with BCR-ABL-targeting tyrosine kinase inhibitors for future application to increase therapeutic efficacy."

Journal • Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia • Oncology

[VIRTUAL] Deciphering the functional basis of synergy between taxanes and TAK715: A novel repurposed drug candidate in treatment-refractory aggressive prostate cancer (AACR 2021) - "Finally, using single-cell transcriptomic analysis we showed that cell subpopulations expressing the PCa stemness marker CD44, or drug resistant markers (CXCL8, CDK1), or epithelial-to-mesenchymal transition markers (Vimentin, TGFB1) were also very high expressors of TAK715 target genes (CSNK1D, MAPK14, MAP4K4) indicating TAK715 is potentially effective against treatment-refractory and stem-cell like subclones.Together, we conclude that TAK715+Taxane combination may be useful in curbing oncogenic progressions in AVPCa through simultaneous inhibition of multiple oncogenic factors/ pathways. Currently, we are performing functional analysis of microRNA signatures of drug synergy as well as in vivo validation of the drug combinations using mouse xenograft models."

Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • CD44 • CDK1 • CXCL8 • MIR132 • MIR21 • PTEN • TGFB1 • VIM