Figure 1.
Many putative BH3 mimetics do not kill like BH3-only proteins
A: The viability of wild-type MEFs (WT) or Bax- and Bak-deficient MEFs (DKO) 24 h after infection with the indicated retroviruses. Expression of the cDNA encoding the BH3-only protein BimS or tBid was linked by an IRES to that of GFP, and the viability of GFP+ve cells determined by PI exclusion.
B: Representative wells showing colony formation by wild-type (WT) or Bax/Bak-deficient (DKO) MEFs after infection with the control parental retrovirus or one expressing BimL.
C–H: The viability (% cells excluding PI) of WT or Bax- and Bak-deficient (DKO) MEFs treated for 24 h with graded doses of the indicated putative BH3 mimetics.
I: Colonies formed by wild-type (WT) or Bax/Bak-deficient (DKO) MEFs in the presence of no treatment, HA14-1 or Antimycin A.
J: The relative affinities (IC50 in nM) of a BimBH3 peptide (as previously reported; Chen et al., 2005) and several putative BH3 mimetic compounds for Bcl-2 and/or Bcl-w. The affinities were measured in solution competition assays (Chen et al., 2005).
Data in A and C–H represent means ± SD from 3 independent experiments.