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ACBI3

2D structure
Target KRAS 
Mode of action PROTAC degrader
Control cis-ACBI3
Recommended cellular usage concentration 1-10 µM
In vivo use Yes
Donated by Dundee University


Probe criteria


Inhibitor/agonist potency: goal is < 100 nM (IC50, KD) Surface plasmon resonance (SPR): KRASG12D GDP (KD = 5 ± 1 nM; n = 3), KRASG12V GDP (KD = 4 ± 1 nM; n = 3)
Fluorescence polarization (FP): VCB+KRASG12D (KD = 4 ± 1 nM; n = 3)
Selectivity within target family: > 30-fold Whole cell proteomics MS analysis of GP2d cells: selective degradation of KRAS. HRAS (log2 fold change -0.0006, -logP 0.001) and NRAS (log2 fold change -0.12, -logP 0.52) levels are not significantly affected.
Selectivity outside target family Whole cell proteomics MS analysis of GP2d cells: clean
On target cell activity for cell-based targets: goal is < 1 µM IC50/EC50 Cellular KRASG12D degradation (24 h, GP5d cells): DC50 = 2 nM; Cellular KRASG12V degradation (24 h, SW620 cells): DC50 = 7 nM (Assay: capillary electrophoresis using the following antibodies: KRASG12D, KRASG12V, normalized by GAPDH)
Cellular proliferation (5 days): GP5d cells (IC50 = 5 nM), SW620 cells (IC50 = 15 nM) (CellTiterGlo assay)
Control compound (100 times less potent than the probe) cis-ACBI3: Cellular KRASG12D degradation (24 h, GP5d cells): DC50 > 1 µM; Cellular proliferation (5 days): GP5d cells (IC50 > 1 µM)