Przejdź do zawartości
Merck

Utilizing PROTAC technology to address the on-target platelet toxicity associated with inhibition of BCL-XL.

Chemical communications (Cambridge, England) (2019-11-23)
Xuan Zhang, Dinesh Thummuri, Yonghan He, Xingui Liu, Peiyi Zhang, Daohong Zhou, Guangrong Zheng
ABSTRAKT

BCL-XL, an anti-apoptotic BCL-2 family protein, plays a key role in cancer cell survival. However, the potential of BCL-XL as an anti-cancer target has been hampered by the on-target platelet toxicity because platelets depend on BCL-XL to maintain their viability. Here we report the development of a PROTAC BCL-XL degrader, XZ424, which has increased selectivity for BCL-XL-dependent MOLT-4 cells over human platelets compared with conventional BCL-XL inhibitors. This proof-of-concept study demonstrates the potential of utilizing a PROTAC approach to achieve tissue selectivity.

MATERIAŁY
Numer produktu
Marka
Opis produktu

Sigma-Aldrich
Apyrase from potato, recombinant, expressed in Pichia pastoris, ATPase ≥1000 units/mg protein, lyophilized powder