A Small Molecule that Induces Intrinsic Pathway Apoptosis with Unparalleled Speed

Cell Rep. 2015 Dec 1;13(9):2027-36. doi: 10.1016/j.celrep.2015.10.042. Epub 2015 Nov 19.


Apoptosis is generally believed to be a process that requires several hours, in contrast to non-programmed forms of cell death that can occur in minutes. Our findings challenge the time-consuming nature of apoptosis as we describe the discovery and characterization of a small molecule, named Raptinal, which initiates intrinsic pathway caspase-dependent apoptosis within minutes in multiple cell lines. Comparison to a mechanistically diverse panel of apoptotic stimuli reveals that Raptinal-induced apoptosis proceeds with unparalleled speed. The rapid phenotype enabled identification of the critical roles of mitochondrial voltage-dependent anion channel function, mitochondrial membrane potential/coupled respiration, and mitochondrial complex I, III, and IV function for apoptosis induction. Use of Raptinal in whole organisms demonstrates its utility for studying apoptosis in vivo for a variety of applications. Overall, rapid inducers of apoptosis are powerful tools that will be used in a variety of settings to generate further insight into the apoptotic machinery.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Apoptosis* / drug effects
  • Caspase 3 / chemistry
  • Caspase 3 / genetics
  • Caspase 3 / metabolism
  • Cell Line, Tumor
  • Complement C8 / deficiency
  • Complement C8 / genetics
  • Cyclopentanes / chemistry*
  • Cyclopentanes / pharmacokinetics
  • Cyclopentanes / toxicity
  • Embryo, Nonmammalian / metabolism
  • Fas-Associated Death Domain Protein / deficiency
  • Fas-Associated Death Domain Protein / genetics
  • Fluorenes / chemistry*
  • Fluorenes / pharmacokinetics
  • Fluorenes / toxicity
  • Half-Life
  • Humans
  • Jurkat Cells
  • Membrane Potential, Mitochondrial / drug effects
  • Mice
  • Mice, Inbred C57BL
  • Mitochondria / metabolism
  • RNA Interference
  • RNA, Small Interfering / metabolism
  • Zebrafish


  • Complement C8
  • Cyclopentanes
  • FADD protein, human
  • Fas-Associated Death Domain Protein
  • Fluorenes
  • RNA, Small Interfering
  • raptinal
  • Caspase 3