Compound class: Synthetic organic

Comment: Supratinib is an amphiphilic molecular analogue of the MEK inhibitor selumetinib [2]. Structurally it is selumetinib linked to a cholesterol-based tether that ficilitates its assembly into a stable supramolecular lipid bilayer nanoparticle. Supratinib was designed to form lipid nanoparticles which would deliver improved MEK-driven anti-cancer activity compared to the parent molecule. It is predicted that such a supramolecular therapeutic could be designed to include immune check point T cell activating biologics (e.g. anti-PD-1 or anti-PD-L1 monoclonal antibodies) which could ultimately be used to enhance cancer immunotherapy.
This same strategy of derivatizing a kinase inhibitor with a cholesterol anchor (in this case creating an analogue of the CSF1R inhibitor sotuletinib) and assembling it in a supramolecular structure with a macrophage-targeting anti-SIRPα mAb (which blocks the SIRPα/CD47 anti-phagocytic signal that is exploited by some cancer cells to avoid immune destruction) has been reported to enhance phagocytosis and removal of melanoma cancer cells by tumour associated macrophages in vitro and in vivo [1].