digitonin

Digitonin is a natural product of the glycoside family and is a detergent. Digitonin has antitumor activity, binds to cholesterol molecules to increase the permeability of cell membranes, and is active in the cleavage of cell membranes in a wide range of cells.

BCL-XL-IN-3 (Compound 11) is an inhibitor of BCL-XL, with a Ki of less than 0.01 nM. It suppresses cell viability in both normal Molt-4 cells and digitonin-permeabilized Molt-4 cells, with EC50 values of 77.8 nM and 0.07 nM, respectively. BCL-XL-IN-3 can be utilized as an ADC toxin for synthesizing Clezutoclax.

MRL-SYKi is a highly selective and potent chemical probe for spleen tyrosine kinase (SYK). In live cell assays, it strongly binds to SYK gain-of-function (GoF) variants [SYK(S550Y), SYK(S550F), and SYK(P342T)], with IC50 values of 2.1 nM, 14 nM, and 4.6 nM in digitonin-permeabilized cell experiments. MRL-SYKi effectively reduces catalytic activity, as shown in PhosphoSens SOX peptide assays, where the IC50 for SYK(S550F) is 63 nM and for SYK(P342T) is 95 nM. Additionally, it decreases phosphorylation levels at Y525/526 of SYK(S550Y) in SW480 cells. MRL-SYKi is useful for inflammation research.