Glomulin Inhibitors

Glomulin, a protein encoded by the GLMN gene, serves as an essential modulator of angiogenesis and is involved in the regulation of various cellular processes, including proliferation and migration. Its function primarily revolves around the inhibition of HIF1A, a transcription factor crucial for hypoxia-induced gene expression. Glomulin binds to the C-terminal activation domain of HIF1A, preventing its interaction with transcriptional coactivators and thus suppressing the transcriptional activity of HIF1A. This inhibition of HIF1A by Glomulin serves as a key regulatory mechanism in controlling angiogenesis and cellular responses to hypoxic conditions.

The inhibition of Glomulin primarily involves targeting the proteasomal degradation pathway. Proteasome inhibitors such as MG132, Bortezomib, and Carfilzomib prevent the breakdown of Glomulin by the proteasome, leading to its accumulation within the cell. This accumulation enhances the inhibitory effects of Glomulin on HIF1A, further suppressing angiogenesis and cellular responses to hypoxia. Additionally, selective inhibitors like ONX-0914 target the immunoproteasome, impacting the degradation of Glomulin and contributing to its intracellular accumulation. By inhibiting the degradation of Glomulin, these compounds offer a strategy for modulating angiogenesis and cellular responses under hypoxic conditions.