DS21360717 is an Orally Active FER Tyrosine Kinase Inhibitor
Posted On 2019-07-06
FER (Proto-oncogene tyrosine-protein kinase) is a kind of non-transmembrane receptor tyrosine kinases. It regulates cell-cell adhesion, involves in signaling from cell surface to the cytoskeleton through growth factor receptors.
In breast cancers, FER expression exhibits high levels. This expression does not depend on prognostic factors. FER protein regulates cell migration and metastasis. This indicates that FER may become the target in the research of cancer. Therefore, a highly potent FER inhibitor is a need for the treatment of cancer.
Recently, Toru Taniguchi, et al. discovered a potent inhibitor of FER with the name DS21360717. They found that the compound has great anti-tumor activity.
Above all, researchers screened a series of pyridine derivatives. These products share a similar structure and may function similarly. As a result, Compound 21 (DS21360717) stands out among these analogs.
DS21360717 is a potent FER inhibitor, with an IC50 of 0.49 nM. In FER-driven Ba/F3 cells, DS21360717 also exhibits great inhibitory activity, with GI50 of 1.9 nM. And in Ba/F3-Mock, the GI50 value is 220 nM.
In addition to the excellent in vitro activity, DS21360717 shows a great effect on the animal assay.
DS21360717 has good oral bioavailability in mice. Researchers administered DS21360717 to mice bearing Ba/F3- FER. The doses range from 12.5 mg/kg to 100 mg/kg. As expected, DS21360717 dramatically inhibits the increase of tumor volume without obvious bodyweight loss.
DS21360717 is a potent and orally active FER inhibitor, with great anti-tumor activity. I hope it will play an important role in cancer treatment in the future.
1. Taniguchi T, et al. ACS Med Chem Lett. 2019 Mar 15;10(5):737-742.