Hello all,

I’m currently exploring the topic of polypharmacy and am particularly interested in the computational challenges of multi-target drug design.

• How difficult is it to design drugs in silico that are intended to bind to more than one receptor target?
• Specifically, what are the best approaches when there is no clear consensus pharmacophore shared across the targets?

My interest stems from the fact that many antipsychotic drugs used to treat conditions like schizophrenia already show affinity for multiple receptor types (e.g., 5-HT2A, D2), often with unwanted side effects resulting from interactions with other receptors such as M1 or A2A.

• Any success stories of drugs that were meant to target more than one receptor subclass or are we always destined to rely on polypills instead of polyactive compounds?

I would appreciate any insights, experiences, or references to successful methodologies in this area.

Thank you in advance!