ABSTRACT
The present disclosure provides compositions and methods for selectively killing senescent cells, wherein the composition comprises a compound of Formula (I) or a compound of Formula (II). The selective killing of senescent cells may delay aging and/or treat age-related disorders.
CLAIMS
1. The compound of the formula:
BCL-L-E3 wherein, BCL is a protein targeting unit which binds to one or more anti-apoptotic Bcl-2 family proteins; E3 is an E3 ubiquitin ligase binding unit which binds to the CRBN or VHL E3 ubiquitin ligase; and L is a linker unit with two ends, each of which covalently links to one of BCL and E3 through one or more of the following functional groups: alkyl, branched alkyl, ether, thioether, ester, amine, amide, carbamate, carbamide, sulfone, aryl, heteroaryl, cycloalkyl, or heterocycle; wherein the linker comprises two ends, wherein each of the two ends are the same or different; wherein the linker unit comprises a length of 1-30 atoms, and wherein the compound has the following chemical structure: where R1 is NO2 or SO2CF3; where R2 is one of the following: where R3 is one of the following: where R4 is one of the following, wherein the bond between R4 and the remainder of BCL is indicated by a and the bond between R4 and L is indicated by β: where E3 has one of the following structures: where R6 and R7 are both or R6 is and R7 is H.