Chapter 10: Preclinical. A Repurposed Novel Lyn Kinase Activator, MLR-1023, is a Model Example of Pharmacological Pleiotropy

The drug discovery and development process is notoriously wrought with a high failure rate. A key contributor to this phenomenon is our significantly incomplete understanding of the biological systems that we are manipulating. We propose that an element of this lack of understanding is the degree to which the therapeutic targets that are modulated by drugs that we work with are involved in more biology, and thereby more therapeutic potential, than most investigators appreciate. This is reflected in the high rate at which drugs are used for indications other than the ones for which they were originally developed. We have coined this phenomenon of multi-therapeutic application for a single drug, pharmacological pleiotropy. MLR-1023, with its activation of Lyn kinase, provides an excellent illustration of pharmacological pleiotropy. Here we provide several examples detailed with scientific understanding across diverse therapeutic space, animal model validation in every case, and with at least two instances of clinical validation. The story also serves as a good example of the fact that there is much more to successful drug discovery and development beyond accomplishing the already arduous task of clinically proving that a drug is safe, well tolerated, and effective for the intended indication.