Deltarasin hydrochloride is a selective inhibitor of KRAS-PDEδ interaction with IC50 value of 41±12 nM [1].
KRAS, also known as V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog, is a protein and works as a molecular on/off switch whose mutant is an essential step in the development of many cancers. PDEδ (prenyl binding protein) controls the spatial organization of K-Ras, which enhances Ras diffusion in the cytosol. Inhibition of the Ras-PDEδ interaction by small molecules impairs Ras localization and signaling has becoming a promising strategy to treat cancers in clinic [1, 2].
Deltarasin hydrochloride is a potent KRAS-PDEδ interaction inhibitor. When tested with human pancreatic ductal adenocarcinoma cells Deltarasin hydrochloride showed inhibition on KRAS-PDEδ interaction to inhibit oncogenic RAS signaling and suppressed cell proliferation by binding to PDEδ with Kd value of 41 nM [1].
In nude mice model with Panc-Tu-I xenograft, administration of Deltarasin hydrochloride (10, 15 mg/kg) impaired cells growth and decreased tumor volume after 9 days in a dose-dependent manner [1].
References:
[1]. Zimmermann, G., et al., Small molecule inhibition of the KRAS-PDEdelta interaction impairs oncogenic KRAS signalling. Nature, 2013. 497(7451): p. 638-42.
[2]. The KRAS-PDEdelta interaction is a therapeutic target. Cancer Discov, 2013. 3(7): p. Of20.