K-Ras-PDEδ-IN-1

K-Ras-PDEδ-IN-1 is a novel and potent competitive K-Ras-PDEδ inhibitor. K-Ras-PDEδ-IN-1 binds to the farnesyl binding pocket of PDEδ with a low nanomolar K_d of 8 nM^[1]. In Vitro: K-Ras-PDEδ-IN-1 exhibits an IC₅₀ value of 12.3 μM in PaTu8902/Panc1 CTG assay^[1].
In Vivo: K-Ras-PDEδ-IN-1 (oral or intraperitoneal?injection; 10 mg/kg; single dose) is in different vehicles (A=5% Tween-80, 50% NaCl, 45% H2O; B=20% DMSO, 80% PEG200; C=15% DMSO, 9.5% Cremophor EL/EtOH (1:1), 75.5 % H2O) for oral and intraperitoneal (IP) administration.whereas only very low compound levels are found in plasma after oral dosage, but significantly higher plasma concentrations are found after IP administration in vehicle A, B or C at 10 mg kg^[1].
K-Ras-PDEδ-IN-1 (intravenous?injection; 3 mg kg; single dose; 24 hours) shows a significant increase of the plasma exposure as well as the terminal half-life (t_1/2=0.4 hours)when compares to compound 93,exhibits a t_1/2, CO, AUC_0-tz, AUC_0.inf-obs, Cl_obs, and Vss_0-inf-obs values of 4.1 hours, 2790.9 ng/ml, 1646.4 h.ng/ml, 1662.5 h.ng/ml, 1.8 L/h/kg, 5.9 l/kg^[1].