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Accessible Unlicensed Requires Authentication Published by De Gruyter 2019

2. SMALL MOLECULES: THE PAST OR THE FUTURE IN DRUG INNOVATION?

Anne Robert, Françoise Benoit-Vical, Yan Liu and Bernard Meunier

Abstract

With the impressive development of molecular life sciences, one may have the feeling that biopharmaceuticals will dominate the world of drug design and production. This is partly due to the evolution of pharmaceutical industry, especially since the 1980s. As a matter of fact, small molecules are still dominating the field of drug innovation, in contradiction with claims predicting their downfall and the exponential raise of biopharmaceuticals. The strong association of chemistry with biochemistry and pharmacology has been the scientific base of the establishment and the success of strong powerful pharmaceutical companies throughout the twentieth century. To meet the needs of new therapeutic agents, it is necessary to assess the role and future position of medicinal chemistry. In fact, the reasonable balance between small molecules and biopharmaceuticals will depend on scientific and economic factors, including the goal of having highly efficient drugs to cure the largest possible number of patients, at a cost that is compatible with the limits of national health budgets. In the present chapter, we would like to emphasize the future important role of small molecules based on new chemicals, to build a new portfolio of efficient, safe and affordable drugs to solve major therapeutic challenges. Two examples are then given. In the blood parasitic diseases such as malaria and schistosomiasis, the iron of heme is an “old” and relevant therapeutic target to kill the parasite. Investigations on the mechanism of action of the antimalarial endoperoxide sesquiterpene artemisinin, have paved the way to the design of new efficient synthetic endoperoxide drugs. In the case of Alzheimer’s disease, the loss of copper homeostasis in patient brain is one of the key features of neurodegeneration. The development of small copper specific ligands able to retrieve copper from its pathological sinks to reintroduce it into physiological circulation is a challenging but promising approach to effective therapy.

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