6RK73 / Mission Therap - LARVOL DELTA

UCHL1 Promotes M1 Macrophage Polarization and Inflammation in Chronic Rhinosinusitis by Stabilizing HIF-1α. (PubMed, Cell Biochem Biophys) - "Suppression of UCHL1, via genetic knockdown or pharmacologic inhibition (6RK73), attenuated M1 macrophage polarization and curtailed the production of IL‑1β, TNF‑α and IL‑6 in both cellular and animal models...In a murine CRS model, pharmacological inhibition of UCHL1 significantly ameliorated histopathological injury, reduced behavioral symptoms such as sneezing and nasal scratching, and lowered IgE levels, and pro‑inflammatory cytokines, while downregulating the UCHL1/HIF‑1α axis and M1 marker expression. Collectively, these findings indicate that UCHL1 drives M1 macrophage polarization and exacerbates CRS inflammation by stabilizing HIF‑1α through deubiquitination, highlighting UCHL1 as a potential therapeutic target in CRS."

Journal • Inflammation • Otorhinolaryngology • Respiratory Diseases • Sinusitis • Targeted Protein Degradation • HIF1A • IL1B • TNFA • UCHL1

Catalpol and tetramethylpyrazine relieve Alzheimer's disease by facilitating AQP4 protein expression and polarized distribution in hippocampal astrocytes via inducing the STAT3-mediated UCHL1 expression. (PubMed, Naunyn Schmiedebergs Arch Pharmacol) - "AD mice were treated with CT, TGN020, 6RK73, and Stattic...CT likely promotes STAT3 phosphorylation, enhancing UCHL1 expression, which in turn facilitates AQP4 expression and its polarized distribution in hippocampal astrocytes, providing therapeutic benefits in AD. These findings suggest CT as a potential therapeutic agent for AD."

Journal • Alzheimer's Disease • CNS Disorders • Dementia • Targeted Protein Degradation • AQP4 • STAT3 • UCHL1

Potential Anti-Cancer Drug 6RK73 Suppresses Ovarian Cancer Growth by Inactivating the AKT1/Sp1 Induced c-Myc Signaling Pathway. (PubMed, J Cancer) - "Finally, AKT1 overexpression reversed the 6RK73-mediated suppression of cell proliferation by reactivating the AKT1/Sp1/c-Myc signaling pathway. These findings suggest that 6RK73 is a promising anti-cancer agent that exerts its effects by inactivating AKT1/Sp1/c-Myc signaling in ovarian cancer."

Journal • Breast Cancer • Genito-urinary Cancer • Oncology • Ovarian Cancer • Renal Cell Carcinoma • Solid Tumor • Targeted Protein Degradation • AKT1 • UCHL1

Deubiquitinase UCHL1 stabilizes KDM4B to augment VEGF signaling and confer bevacizumab resistance in clear cell renal cell carcinoma. (PubMed, Transl Oncol) - "Overall, this study defined an epigenetic mechanism of UCHL1/KDM4B in activating VEGF signaling. The UCHL1-KDM4B axis represents a novel target for treating ccRCC and improving the efficacy of anti-angiogenesis therapy."

Journal • Clear Cell Renal Cell Carcinoma • Colorectal Cancer • Genito-urinary Cancer • Oncology • Solid Tumor • Targeted Protein Degradation • EPAS1 • KDM4B • UCHL1