JWG-071 / Dana-Farber Cancer Institute, Autonomous University of Barcelona - LARVOL DELTA

Identification of a new ERK5 kinase inhibitor (EACR 2025) - "In conclusion, we discovered a new potential ERK5 kinase inhibitor that has an effect at nanomolar concentrations, both in inhibiting ERK5 kinase activity and cell proliferation in an ERK5-dependent manner. Even if further evaluation regarding the capability of this inhibitor not to induce a paradoxical activation of ERK5 will be needed, these results pave the way to a new class of small molecules inhibiting ERK5 activity, that may be able to reach clinical relevance after additional preclinical evaluation."

Hepatocellular Cancer • Oncology • Ovarian Cancer • Solid Tumor

Inhibition of the extracellular signal-regulated kinase 5 (ERK5) increases EGFR expression and its nuclear localization in HCC, generating new targeting opportunities (EACR 2025) - "For the pharmacological treatments, ERK5 (JWG-071), EGFR (Gefitinib) α/β importin (Ivermectin) inhibitors effects were evaluated after 72h of treatment in term of cell viability using MTT assay. In conclusion, these results revealed new potential therapeutic strategies to explore for the treatment of HCC."

Hepatocellular Cancer • Liver Cancer • Oncology • Solid Tumor • EGFR • PI3K

The MEK5/ERK5 pathway promotes the activation of the Hedgehog/GLI signaling in melanoma cells. (PubMed, Cell Oncol (Dordr)) - "MEK5-ERK5 is an activator of GLI transcription factors, and combined targeting of these pathways warrants further preclinical investigation as a potential innovative therapeutic approach for melanoma."

Journal • Genetic Disorders • Melanoma • Oncology • Skin Cancer • Solid Tumor • GLI1 • GLI2

ERK5 is essential for early porcine embryonic development by maintaining Endoplasmic Reticulum homeostasis. (PubMed, Gene) - "In this study, to determine the function of ERK5 during porcine embryo development, ERK5 function was inhibited by adding the ERK5 inhibitor JWG-071...In addition, ERK5 inhibition increased the expression of BAX, a pro-apoptotic gene, resulting in apoptosis. In conclusion, the results show that ERK5 inhibition during porcine embryonic development induces autophagy and apoptosis by increasing ER stress, resulting in a negative effect on embryonic development in pigs."

Journal • Preclinical • ATG7 • BAX • HSPA5

Identification of a Functional Relationship between MEK5-ERK5 Pathway and Hypoxia Inducible Factor 1α (AMP Europe 2023) - "Effects on cell viability of KC7F2 (HIFi) and XMD8-92 or JWG-071 (ERK5i) were evaluated using MTT assay... These findings led to the identification of a relationship between ERK5 and HIF-1α in the regulation of CCA homeostasis, and put light on the combined ERK5/HIF- targeting among the new possible therapeutic options for CCA."

Biliary Cancer • Cholangiocarcinoma • Gastrointestinal Cancer • Hepatocellular Cancer • Hepatology • Liver Cancer • Oncology • Solid Tumor • CA9 • HIF1A • SLC2A1

COMBINED TARGETING OF MEK5/ERK5 AND HEDGEHOG/GLI PATHWAYS IN HUMAN MELANOMA (EACR 2023) - "Chemicals (small molecule inhibitors) used were: the ERK5 inhibitors JWG-071 and AX-15836; MEK5 inhibitors GW284543 and BIX02189; GLI1/2 inhibitor GANT61; SAG, an HH/GLI pathway activator...In melanoma cells, genetic and pharmacological ERK5 inhibition similarly inhibited the expression and activity of GLI proteins. Interesting, the combination of GANT61 with MEK5 inhibitors was more effective than single treatments in reducing the volume of melanoma spheroids.ConclusionCombined targeting of the MEK5/ERK5 and HH/GLI pathways may be a useful approach to prevent resistance mechanisms frequently observed upon monotherapy in melanoma."

Melanoma • Oncology • Solid Tumor • BRAF • GLI1 • GLI2

Study identifies a new therapeutic strategy to tackle endometrial cancer (News-Medical) - "In this work, carried out using cellular and mouse models, the researchers used a new ERK5 inhibitor (JWG-071), currently in preclinical development. They observed that inhibition of the ERK5 protein reduces the proliferation of tumor cells, and it impairs the growth of tumors in animal models. This effect is mediated through NF-κB, a transcription factor that regulates the proliferation and survival of different tumor types, including endometrial cancer."

Preclinical • Endometrial Cancer • Oncology • Solid Tumor