ËÄÉ«AV

A ligand drug conjugate comprising (a) a targeting ligand; (b) a cleavable bridge; and a bromodomain and extra-terminal (BET) inhibitor is provided. The targeting ligand may comprise a cancer targeting ligand. The BET inhibitor may comprise I-BET762, (+)-JQ1, MS417, OXT015, (2), RVX-208, (3), OXFBD02, OXFBD03, I-BET151, (4), PFI-1, I-BET726, MS436, XD14 or a modified BET inhibitor. Modified BET inhibitors are also provided, including RT48 (S-2-(6-(4-chlorophenyl)-8-methoxy-1-methyl-4H-benzo[f][1,2,4]triazolo[4,3-a][1,4]diazepin-4-yl)-1-(4-(dimethylamino)piperidin-1-yl)ethan-1-one) and RT53 ((S)-2-(6-(4-chlorophenyl)-8-methoxy-1-methyl-4H-benzo[f][1,2,4]triazolo[4,3-a][1,4]diazepin-4-yl)-N-(4-(4-(dimethylamino)piperidin-1-yl)phenyl)acetamide). A prodrug of a BET inhibitor is also provided. A method of preparing a ligand drug conjugate according to the invention is also provided. The method comprises (i) functionalize a BET inhibitor with a tertiary amine to form a modified BET inhibitor according to the invention; (ii) bonding the modified BET inhibitor formed in step (i) to a cleavable bridge; and (iii) bonding the cleavable bridge bound to the modified BET inhibitor formed in step (ii) to a targeting ligand. A ligand drug conjugate according to the invention for use as a medicament is also provided.