Table 1.
Compound | M.W. | Discovery method | Direct binding | KD, μM | Binding sites | TOP-Flash, IC50, μM | In vivo efficacy |
---|---|---|---|---|---|---|---|
PNU-74654 | 320 | virtual screening | NMR, ITC | 0.450 | K435, R469 | N.D. | N.D. |
UU-T01 | 230 | hot spot-based design | ITC, mutagenesis | 0.531 | K435, K469 K508 | N.D. | N.D. |
UU-T02 | 665 | peptidomimetic design | ITC, mutagenesis | 0.418 | K435, R469 R474, K508 R515 | SW480: 232 | N.D. |
MSAB | 305 | luciferase-reporter screening | SPR, NMR | N.D. | residues 301–670 | HCT116: 0.58 | 20 mg/kg p.o., q.2d. |
HI-B1 | 255 | rational design based on a hit | protein pull-down | N.D. | K312 | DLD1: 13 CACO2: 13 | 50mg/kg i.p., q.d. |
carnosic acid | 332 | screening by in vitro ELISA | NMR | 5–20 | ARD N-terminus | SW480: ~25 | diet containing 0.1% or 1% carnosate |
PNPB-22 | 646 | hot spot-based design | ITC, mutagenesis | 0.330 | L156, L159, V167, A171, M174, L178 | SW480: 13 | N.D. |
N.D.: not determined. ARD: Armadillo repeat domain.