Many pathological states are multimodal in nature involving several mediators, signaling pathways and molecular mechanisms. Monomodal therapies often fail to provide complete relief or show undesirable side effects.
A molecule with two or more mechanisms of action has the potential to improve efficacy and safety ratio, especially if synergy between the two mechanisms is found
Multimodal Therapy may be a way of improving the R&D output obtained using the “one drug-one target” approach, questioned over the last years.1
Welab has worked in the most innovative approaches to Multimodal Therapy. While mutual prodrugs are challenging in terms of getting the adequate in vivo cleavage and metabolism profile, bivalent ligands are large in nature and thus related to suboptimal ADME properties. Dual small ligands seem to be the best approach to Multimodal Therapy since they offer the potential of
- improving efficacy and safety ratio, especially if synergy between the two mechanisms is found.
- lower risk of drug-drug interactions compared to cocktails or multi-component drugs, thus involving simpler pharmacokinetics and less variability among patients.
- broadening the therapeutic application in relation to mono-mechanistic drugs, by addressing more complex etiologies.
1.Bornot A et al J. Med. Chem, 2013, 56, 1197-1210.