1644443-92-4Relevant academic research and scientific papers
The discovery of potent cRaf1 kinase inhibitors
Lackey, Karen,Cory, Michael,Davis, Ronda,Frye, Stephen V.,Harris, Philip A.,Hunter, Robert N.,Jung, David K.,McDonald, O. Bradley,McNutt, Robert W.,Peel, Michael R.,Rutkowske, Randy D.,Veal, James M.,Wood, Edgar R.
, p. 223 - 226 (2000)
A series of benzylidene-1H-indol-2-one (oxindole) derivatives was synthesized and evaluated as cRaf-1 kinase inhibitors. The key features of the molecules were the donor/acceptor motif common to kinase inhibitors and a critical acidic phenol flanked by two substitutions. Diverse 5-position substitutions provided compounds with low nanomolar kinase enzyme inhibition and inhibited the intracellular MAPK pathway. (C) 2000 Elsevier Science Ltd. All rights reserved.
Dual inhibition of Kif15 by oxindole and quinazolinedione chemical probes
Dumas, Megan E.,Chen, Geng-Yuan,Kendrick, Nicole D.,Xu, George,Larsen, Scott D.,Jana, Somnath,Waterson, Alex G.,Bauer, Joshua A.,Hancock, William,Sulikowski, Gary A.,Ohi, Ryoma
, p. 148 - 154 (2019)
The mitotic spindle is a microtubule-based machine that segregates a replicated set of chromosomes during cell division. Many cancer drugs alter or disrupt the microtubules that form the mitotic spindle. Microtubule-dependent molecular motors that function during mitosis are logical alternative mitotic targets for drug development. Eg5 (Kinesin-5) and Kif15 (Kinesin-12), in particular, are an attractive pair of motor proteins, as they work in concert to drive centrosome separation and promote spindle bipolarity. Furthermore, we hypothesize that the clinical failure of Eg5 inhibitors may be (in part) due to compensation by Kif15. In order to test this idea, we screened a small library of kinase inhibitors and identified GW108X, an oxindole that inhibits Kif15 in vitro. We show that GW108X has a distinct mechanism of action compared with a commercially available Kif15 inhibitor, Kif15-IN-1 and may serve as a lead with which to further develop Kif15 inhibitors as clinically relevant agents.
