Rehabilitating drug-induced long-QT promoters: In-silico design of hERG-neutral cisapride analogues with retained pharmacological activity

Table 1 Selected cisapride analogues from the de Novo drug design study

Ligands	A_2Areceptor docking score (kcal/mole)	hERG1 docking score (kcal/mole)
Cisapride	-8.48	-7.80
Cisapride_Frag_337	-9.46	-4.73
Cisapride_Frag_182	-8.66	-5.34

The 10700 small organic molecules fragment database of Schrodinger was used to create new derivatives of cisapride (the place for replacement was previously found by a trajectory analysis of the MD simulations). Molecules were initially docked using virtual high‒throughput screening (VHTS) with subsequent Glide/XP docking for the promising derivatives (~500 compounds). Finally, the inhibitory profiles of these derivatives at hERG1 were tested using Induced Fit Docking.

ISSN: 2050-6511