1991986-30-1

Usage

Uses

Used in Anticancer Applications:
ML364 is used as an anticancer agent for the treatment of colorectal cancer and mantle cell lymphoma. By inhibiting USP2, ML364 promotes the degradation of cyclin D1, which in turn leads to cell cycle arrest and prevents the uncontrolled proliferation of cancer cells.
Used in Pharmaceutical Research:
ML364 is used as a research tool in the development of novel therapeutic strategies targeting the USP2-deubiquitinase pathway. Its ability to modulate the cell cycle and induce cell cycle arrest in cancer cells makes it a valuable compound for studying the underlying molecular mechanisms of cancer progression and identifying potential therapeutic targets.
Used in Drug Development:
ML364 serves as a starting point for the development of new drugs targeting USP2 and its associated pathways. Its inhibitory effect on USP2 can be further optimized and modified to improve its potency, selectivity, and pharmacokinetic properties, potentially leading to the development of more effective anticancer drugs.

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Relevant academic research and scientific papers

Small molecule inhibition of the ubiquitin-specific protease USP2 accelerates cyclin D1 degradation and leads to cell cycle arrest in colorectal cancer and mantle cell lymphoma models

Deubiquitinases are important components of the protein degradation regulatory network. We report the discovery of ML364, a small molecule inhibitor of the deubiquitinase USP2 and its use to interrogate the biology of USP2 and its putative substrate cyclin D1. ML364 has an IC50 of 1.1 μM in a biochemical assay using an internally quenched fluorescent di-ubiquitin substrate. Direct binding of ML364 to USP2 was demonstrated using microscale thermophoresis. ML364 induced an increase in cellular cyclin D1 degradation and caused cell cycle arrest as shown in Western blottings and flow cytometry assays utilizing both Mino and HCT116 cancer cell lines. ML364, and not the inactive analog 2, was antiproliferative in cancer cell lines. Consistent with the role of cyclin D1 in DNA damage response, ML364 also caused a decrease in homologous recombination-mediated DNA repair. These effects by a small molecule inhibitor support a key role for USP2 as a regulator of cell cycle, DNA repair, and tumor cell growth.