AZD8330 / AstraZeneca, Pfizer - LARVOL DELTA

A drug discovery pipeline for MAPK/ERK pathway inhibitors in C. elegans. (PubMed, Cancer Res Commun) - "Using fluorescence-based image analysis of vulva development as a readout for MAPK/ERK activity, we obtained excellent assay Z-scores for the MEK inhibitors trametinib (Z = 0.95), mirdametinib (Z = 0.93), and AZD8330 (Z = 0.87), as well as the ERK inhibitor temuterkib (Z = 0.86). To validate the model in a high throughput setting, we screened a blinded library of 433 anti-cancer compounds and identified four MEK inhibitors among seven positive hits. Our results highlight a high degree of pharmacological conformity between C. elegans and human MAPK/ERK pathways and the presented high-throughput pipeline may discover and characterize novel inhibitors in vivo."

Journal • Oncology

Integrating bulk and single-cell RNA sequencing data reveals epithelial-mesenchymal transition molecular subtype and signature to predict prognosis, immunotherapy efficacy, and drug candidates in low-grade gliomas. (PubMed, Front Pharmacol) - "In addition, several promising drugs, including birinapant, fluvastatin, clofarabine, dasatinib, tanespimycin, TAK-733, GDC-0152, AZD8330, trametinib and ingenol-mebutate had great potential to the treatment of high risk patients. Our research revealed non-negligible role of EMT in the TME diversity and complexity of LGG. A prognostic signature may contribute to the personalized treatment and prognostic determination."

IO biomarker • Journal • Brain Cancer • CNS Tumor • Glioma • Oncology • Solid Tumor • SLC39A1

Multi-omics analysis reveals CLIC1 as a therapeutic vulnerability of gliomas. (PubMed, Front Pharmacol) - "High CLIC1 expression samples were more sensitive to camptothecin, cisplatin, doxorubicin, erlotinib, paclitaxel, rapamycin, clofarabine, tanespimycin, methotrexate, everolimus, TAK-733, trametinib and AZD8330. Single-cell analysis unveiled that CLIC1 was expressed ubiquitously in tumor cells and tumor microenvironment. Overall, CLIC1 was a promising treatment vulnerability in glioma."

Journal • Brain Cancer • CNS Tumor • Glioma • Oncology • Solid Tumor • CLIC1

Upregulation of cIAP1 induced by AZD8330 alleviates osteoarthritis progression by inhibiting the RIP1-associated necrosis signaling pathway. (PubMed, Int Immunopharmacol) - "Our study provides compelling evidence attesting to the capacity of AZD8330 in managing inflammation within the realm of OA treatment. Likewise, our study has elucidated that the attenuation of OA by AZD8330 relies on the activation of cIAP1 to inhibit RIP1, consequently suppressing the NF-κB signaling pathway. On the strength of our present study, we may have identified a viable drug candidate for OA treatment."

Journal • Immunology • Inflammation • Osteoarthritis • Pain • Rheumatology • RIPK1 • TNFA

MEK 1/2 inhibitors in the treatment of gynecologic malignancies (Gynecol Oncol) - “This paper reviews the translational evidence in favor of MEK inhibitors in cancer, their role in gynecologic malignancies, and details regarding the status of the fourteen MEK inhibitors currently being clinically tested: trametinib, selumetinib, pimasertib, refametinib, PD-0325901, MEK162, TAK733, RO5126766, WX-554, RO4987655, cobimetinib, AZD8330, MSC2015103B, and ARRY-300.” 

Review • Oncology

Cachexia: Leveraging transcriptomics to identify potential therapeutics (AACR 2018) - "The thermo-stimulatory signature is most strongly reversed by expression signatures from inhibitors of MEK (MAP2K1), including pd-0325901, AZD-8330 (ARRY-704), CI-1040, trametinib, and selumetinib. Interestingly, we observe a time-dependent effect of these MEK inhibitors, with shorter durations of exposure consistently reversing thermo-stimulatory signatures more effectively than longer durations of exposure.Analysis of cachexia-related transcriptomic data reveals key marker genes and pathways which can be used to optimize MEK inhibitors for cachexia. Results from this study support the development of MEK inhibitors to treat cachexia, and suggest that careful optimization of pharmacokinetics will be important for success in the clinic."

Gastric Cancer • Lung Cancer

B7-H6 Promotes Cell Proliferation, Migration and Invasion of Non-Hodgkin Lymphoma via Ras/MEK/ERK Pathway Based on Quantitative Phosphoproteomics Data. (PubMed, Onco Targets Ther) - "Strikingly, MEK inhibitor AZD8330 was found to have the ability to sufficiently inhibit Ras/MEK/ERK pathway, partially reverse cell proliferation and completely reverse cell migration and invasion induced by B7-H6. B7-H6 promotes cell proliferation, migration and invasion in NHL via Ras/MEK/ERK pathway. Hence, B7-H6 or Ras/MEK/ERK pathway targeting may be used as potential therapeutics for treating NHL."

Journal • Diffuse Large B Cell Lymphoma • Hematological Disorders • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • HIF1A