A Potent and Selective Quinoxalinone-Based STK33 Inhibitor Does Not Show Synthetic Lethality in KRAS-Dependent Cells was written by Weiwer, Michel;Spoonamore, James;Wei, Jingqiang;Guichard, Boris;Ross, Nathan T.;Masson, Kristina;Silkworth, Whitney;Dandapani, Sivaraman;Palmer, Michelle;Scherer, Christina A.;Stern, Andrew M.;Schreiber, Stuart L.;Munoz, Benito. And the article was included in ACS Medicinal Chemistry Letters in 2012.Quality Control of 5-Isopropylindoline-2,3-dione This article mentions the following:
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-mol. inhibitors of STK33 might selectively target KRAS-dependent cancers. To test this hypothesis, we initiated a high-throughput screen using compounds in the Mol. Libraries Small Mol. Repository (MLSMR). Several hits were identified, and one of these, a quinoxalinone derivative, was optimized. Extensive SAR studies were performed and led to the chem. 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-mol. STK33 inhibitors. Small mols. having different chem. 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-mol. probes of STK33. In the experiment, the researchers used many compounds, for example, 5-Isopropylindoline-2,3-dione (cas: 150560-58-0Quality Control of 5-Isopropylindoline-2,3-dione).
5-Isopropylindoline-2,3-dione (cas: 150560-58-0) belongs to indole derivatives. Indole, also called Benzopyrrole, a heterocyclic organic compound occurring in some flower oils, such as jasmine and orange blossom, in coal tar, and in fecal matter. They are capable of binding to a variety of receptors with high affinity and thus have applications in a wide range of therapeutic areas.Quality Control of 5-Isopropylindoline-2,3-dione
Referemce:
Indole alkaloid derivatives as building blocks of natural products from Bacillus thuringiensis and Bacillus velezensis and their antibacterial and antifungal activity study,
Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles