Our pre-track work with ‘in vitro suitable’ bivalent ligands suggests an improved therapeutic benefit over classic steroids used in the clinic for the treatment of the blood cancer multiple myeloma. We aim to gather industrially relevant in vivo proof-of-concept data with ‘in vivo suitable’ bivalent ligands. To achieve this goal, we will  chemically synthesize amide-based in vivo counterparts of currently six functional bivalent ligands. This entails coupling an agonist for a first nuclear receptor to an antagonist for a second nuclear receptor via six different (medchem-compatible) linkers. We will  biologically validate the novel ligands for anti-myeloma cell killing activity using well-characterized cell lines. Max. two top-ranked ligands will undergo eADMET tests and be evaluated in vivo in a myeloma xenograft model for tumor growth and side effects. In short, we will collect in vivo proof-of-concept data to attract pharmaceutical partners and generate intellectual property.