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A Small Molecule That Induces Intrinsic Pathway Apoptosis With Unparalleled Speed

A Small Molecule That Induces Intrinsic Pathway Apoptosis With Unparalleled Speed

Rahul Palchaudhuri, Michael J Lambrecht, Rachel C Botham, Kathryn C Partlow, Tjakko J van Ham, Karson S Putt, Laurie T Nguyen, Seok-Ho Kim, Randall T Peterson, Timothy M Fan, Paul J Hergenrother

Cell Rep. 2015 Dec 1;13(9):2027-36.

PMID: 26655912

Abstract:

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.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP1176096	Raptinal		1176-09-6	Price

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