| Description |
Deltarasin hydrochloride is an inhibitor of KRAS-PDEδinteraction with Kd of 38 nM for binding to purified PDEδ.
|
| Related Catalog |
|
| Target |
Kd: 38 nM (PDEδ)
|
| In Vitro |
In liver cells, deltarasin inhibits the interaction of RAS with PDEδ with KD of 41 nM. Inhibition of PDEδ-KRAS interaction by deltarasin suppresses proliferation of human pancreatic ductal adenocarcinoma cells that are dependent on oncogenic KRAS[1].
|
| In Vivo |
Deltarasin (10 mg/kg, i.p.) impairs dose-dependent tumor growth in nude mice bearing subcutaneous human Panc-Tu-I tumour cell xenografts[1].
|
| Kinase Assay |
KD values are measured by fluorescence polarization measurements. For direct titrations, increasing amounts of PDEδ are added to a solution containing 50-100 nM labelled small molecule in 200 µL PBS buffer. For displacement titrations, increasing amounts of the small molecules in DMSO are directly added to fluorescein-labelled atorvastatin (24 nM) and His6-tagged PDEδ (40 nM) in 200 µL PBS-buffer (containing 0.05% CHAPS, 1% DMSO), keeping the concentration of fluorescein-labelled atorvastatin, PDEδ and DMSO constant. For KD measurements using isothermal titration calorimetry, PDEδ protein (280 µM) is titrated to small molecule (30 µM) in Tris/HCl buffer (temperature 25°C). In the Tm shift assays, protein melting points are detected by circular dichroism spectroscopy in the presence of small molecules.
|
| References |
[1]. Zimmermann G, et al. Small molecule inhibition of the KRAS-PDEδ interaction impairs oncogenic KRAS signalling. Nature. 2013 May 30;497(7451):638-42.
|
