A large body of research exists on the inhibition of ABC Transporters in tumor tissues (e.g., chemotherapeutic drugs) and micro-organisms (e.g., antibiotics) in order to maintain effective drug levels within cells. Limerick has shifted this paradigm. Our expertise has enabled us to begin decreasing intracellular concentrations of toxic substances (e.g. immunosuppressants in unintended tissues and organs). This alteration of drug or endogenous substance re-distribution is possible through the activation of ABC Transporters at non-targeted organs.
Most drugs and endogenous substances are taken up from the systemic circulatory system into many organs, including organs that are not the primary target. Excessive exposure of some of these exogenous and endogenous substances can lead to organ toxicities. Through the activation of ABC Transporters, our Activators enhance the efflux of drugs or unwanted endogenous substances out of non-targeted organs back into the blood for improved therapeutic effect or for elimination. This type of drug or chemical re-distribution protects vulnerable organs from many toxicities.
Through an efficient discovery and development strategy, Limerick has created a pipeline of proprietary and clinic-ready Activators. These Activators target localized or diffuse protective pumps.
Limerick Activators in Immunosuppression
Unintended side effects of the anti-rejection calcineurin inhibitors (CNIs) are hyperglycemia, CNS irritability, and nephrotoxicity. These side effects are directly related to localization of the CNIs in the pancreas, brain, and kidney. In our pre-clinical studies with CNIs, Limerick Activators mitigate CNI-induced hyperglycemia and nephrotoxicity while maintaining immunosuppressive effects. LIM-0705, an NCE Activator has completed a Phase I human clinical study with tacrolimus, a commonly used CNI.
Limerick Activators in Metabolic Disease
Accumulation of intracellular lipids leads to diseases such as diabetes and hyperlipidemia. In preclinical studies, our metabolic Activators are demonstrating improvement in lipid and glucose homeostasis. In recent experiments, our Activators increased efflux of lipids from peripheral and pancreatic beta cells, resulting in lowering of serum lipid and glucose. We continue our focused efforts to develop lead molecules to take to the clinic in a metabolic disease indication.
We believe that our approach offers substantial opportunities to:
- Improve the safety profile of both marketed and investigational drugs
- Address diseases such as metabolic disorders
- Significantly improve the quality of life for patients
