Deltarasin

Short Summary : KRAS-PDEδ interaction inhibitor

Category : Metabolism|KRAS-PDEδ

Purity : 0.98

CAS Number : 1440898-61-2

Formula : C40H37N5O

Molecular Weight : 603.75

SMILE : [H][C@@](C1CCNCC1)(N2C3=CC=CC=C3N=C2C4=CC=CC=C4)COC5=CC=C(C6=NC7=CC=CC=C7N6CC8=CC=CC=C8)C=C5

Solubility : Soluble in DMSO > 10 mM

Storage : Store at -20°C

Description : The KRAS oncogene product is considered a major target in anticancer drug discovery. Interfering with binding of mammalian PDE to KRAS by means of small molecules provides a novel opportunity to suppress oncogenic RAS signalling by altering its localization to endomembranes. Deltarasin is an inhibitor of the KRAS-PDE interaction to impair oncogenic KRAS signalling.
In vitro: Within a minute, 5 mM of deltarasin completely inhibited PDE-KRAS interaction and released the insolubilized mCitrine-RHEB/KRAS6Q to the endomembrane system. This showed that deltarasin interfered with the binding of KRAS to PDE in cells and thereby inhibited its solubilization [1].
In vivo: A clear dose-dependent reduction in Panc-Tu-I tumour growth rate could be observed in deltarasin treated mice with respect to the vehicle-injected controls, where the growth of tumours in mice that were treated with 10mg kg/1 BID deltarasin was almost completely blocked [1].
Clinical trial: No clinical data are available.
Reference:[1] Zimmermann G, Papke B, Ismail S, Vartak N, Chandra A, Hoffmann M, Hahn SA, Triola G, Wittinghofer A, Bastiaens PI, Waldmann H. Small molecule inhibition of the KRAS-PDE interaction impairs oncogenic KRAS signalling. Nature. 2013;497(7451):638-42.

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