1404437-62-2

Usage

Uses

Used in Pharmaceutical Industry:
ML281 is used as an anticancer agent for targeting KRAS-dependent cancers. It works by inhibiting the STK33 protein, which plays a crucial role in the development and progression of these types of cancers. By blocking this protein, ML281 can potentially halt the growth of cancer cells and improve the effectiveness of cancer treatments.
Used in Cancer Research:
ML281 is also used as a research tool in the field of cancer biology. It helps scientists understand the role of STK33 in KRAS-dependent cancers and can be employed to study the underlying mechanisms of these diseases. This knowledge can contribute to the development of new therapeutic strategies and personalized medicine approaches for patients with KRAS-dependent cancers.

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Relevant academic research and scientific papers

A potent and selective quinoxalinone-based STK33 inhibitor does not show synthetic lethality in KRAS-dependent cells

The KRAS oncogene is found in up to 30% of all human tumors. In 2009, RNAi experiments revealed that lowering mRNA levels of a transcript encoding the serine/threonine kinase STK33 was selectively toxic to KRAS-dependent cancer cell lines, suggesting that small-molecule inhibitors of STK33 might selectively target KRAS-dependent cancers. To test this hypothesis, we initiated a high-throughput screen using compounds in the Molecular Libraries Small Molecule Repository (MLSMR). Several hits were identified, and one of these, a quinoxalinone derivative, was optimized. Extensive SAR studies were performed and led to the chemical probe ML281 that showed low nanomolar inhibition of purified recombinant STK33 and a distinct selectivity profile as compared to other STK33 inhibitors that were reported in the course of these studies. Even at the highest concentration tested (10 μM), ML281 had no effect on the viability of KRAS-dependent cancer cells. These results are consistent with other recent reports using small-molecule STK33 inhibitors. Small molecules having different chemical structures and kinase-selectivity profiles are needed to fully understand the role of STK33 in KRAS-dependent cancers. In this regard, ML281 is a valuable addition to small-molecule probes of STK33.