Table 1

Milestones in history of Bcl-2 research

198414; 18 breakpoint cloned
1985–1986Bcl-2 cDNA cloned; sequenced
1988Apoptosis suppression
1989Bcl-2 poor progress in NHL
1990Bcl-2 localized to mitochondria
1992Chemoresistance
1993Bax dimerizes with Bcl-2
1993Bcl-2 over expressed in CLL
1993ASO reverses chemoresistance
1994Mitochondria required
1996BH3 mediates dimerization
1996Bcl-X 3D structure
1997Bcl-2 ASO (Ph3 CLL)
1997Bcl-XL + BH3 3D structure
1997Bcl-2 gene amplified (DLBCL)
1999SAR by NMR
2001Bcl-2 3D structure
2002–2005miR-15/16 deletion (CLL)
2005ABT 737 discovered
2007Bcl-XL required for platelets
2007Obatoclax discovered
2008Navitoclax discovered
2009Obatoclax Ph 1
2011Navitoclax Ph 1
2013Venetoclax discovered
2016Venetoclax impressive activity in R/R CLL
2016FDA approval
  • NOTE: Some of the milestones are listed chronologically in the journey from discovery of the gene encoding Bcl-2 to the FDA approval of the first Bcl-2 inhibitor, venetoclax.