BI-8925: Inhibitor of MLKL protein, a key player in necroptosis, is now available to order on opnMe.com
01 February 2021
The Mixed lineage kinase domain-like protein (MLKL) is the effector protein in the signal pathway leading to necroptosis, an emergency-controlled cell-death mechanism. Necroptosis may be activated in case of impairment of the well-studied controlled cell death mechanism - apoptosis and can be triggered by Tumor necrosis factor (TNF). However, this mechanism can result in release of proinflammatory cytoplasmatic cell contents, causing damage and potentially implicated in disease.
BI-8925 is an inhibitor of the MLKL protein, belonging to the xanthine class. It is the first covalent tool compound for MLKL, with a structurally understood mode of action. It works by stabilizing the inactive state of MLKL by an essential π–π stacking interaction. The molecule is found to inhibit necroptosis in Jurkat and U937 cells with an IC50 of 541 and 271 nM, respectively.
As a researcher, you are now able to obtain BI-8925 and its negative control BI-8762 completely free of charge. You will own all results you will generate with the molecules and may use them for your own publications.
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About BI-8925
MLKL is a key player in the necroptosis pathway, encompassing a C-terminal regulatory and an N-terminal executioner domain. BI-8925 is a covalent in vitro inhibitor of MLKL with a structurally and functionally characterized mode of action and good activity in cells. It acts by stabilizing the packing of α-helix 6 against the four-helix bundle through the formation of a stabilizing π–π-stacking interaction between Phe148 located in α-helix 6 and the xanthine core.
About opnMe:
opnMe.com, the new open innovation portal of Boehringer Ingelheim, aims to accelerate research initiatives to enable new insights of disease biology in areas of high unmet medical need by sharing well-characterized molecules and offer collaborations for science. In the spirit of collaboration, our molecules are provided to the scientific community to help unlock and fulfill their full potential. These molecules are either freely available as “Molecules to Order” or applied via scientific research submissions as “Molecules for Collaboration”. As part of our third pillar, our “opn2EXPERTS” program, we also enlist scientific advice on key biologic issues to fuel further drug discovery and deliver novel solutions that benefit unmet patient needs.