Science Platform

Understanding the Language of Lipids

Lipids are fats and oils which play crucial roles as building blocks, signaling molecules, energy sources, antioxidants, and barriers within cells. Lipids are involved in many physiologic activities and lipidomics is the study of the complete set of lipids within a cell, tissue, or organism. By analyzing the lipidome, valuable insights are gained into lipid signaling pathways in both healthy and disease states.

Cellular Messengers – Lipids transmit messages within and between cells in different ways.

• Lipid mediators, such as endocannabinoids, are lipid-based neurotransmitters that modulate a wide range of physiologic functions, including pain, appetite, mood, and memory.
• Lipids, like diacylglycerol (DAG), are pivotal secondary messengers that are generated in response to extracellular stimuli such as neurotransmitters. They orchestrate intracellular cascades triggering various cellular responses.
• Hormones synthesized from cholesterol regulate diverse physiological functions including reproduction, metabolism, and stress response.
• Certain lipid-derived molecules, such as growth factors, stimulate cell proliferation and differentiation.

Diverse Roles – Lipids are essential components of living organisms. They serve a variety of crucial functions beyond signaling within cells and the body as a whole.

• Structural Components – Phospholipids form the primary structure of cell membranes and organelle membranes, creating a barrier between the inside and outside of the cell or organelle.
• Energy Storage – Triglycerides are the primary energy storage molecules in the body and provide a concentrated source of energy. Fatty acids derived from triglycerides can be broken down to generate Adenosine Triphosphate (ATP), the energy currency of cells.

Abnormal Function – When lipid-signaling pathways are disrupted or dysfunctional, cells may not receive the proper signals to function correctly. This can lead to impaired growth, proliferation, and metabolic processes manifesting in several disease states.

• Cancer – Increased lipid metabolism and signaling can contribute to uncontrolled cell growth and proliferation, a hallmark of cancer. Inflammation – Chronic inflammation can be triggered by dysregulated lipid signaling, leading to various inflammatory diseases.
• Metabolic Disorders – Dysregulation of lipid metabolism can contribute to conditions like obesity, type 2 diabetes, and fatty liver disease.
• Cardiovascular Disease – Abnormal cholesterol levels and altered lipid signaling in blood vessels can promote atherosclerosis, a buildup of plaque that increases the risk of heart attack and stroke.
• Neurodegenerative Diseases – Dysregulation of lipid signaling in the brain has been implicated in the development of Alzheimer’s disease and Parkinson’s disease.

Fatty Acid Binding Proteins (FABPs)

FABPs are a family of intracellular lipid-binding proteins that regulate the transport and metabolism of fatty acids and lipids within cells. There are ten known FABP isoforms in humans (FABP1 through FABP9 and FABP12),¹ Dysregulation of FABPs can lead to excessive lipid binding and contribute to disease states.

Therapeutic Potential of FABP Inhibitors

FABP inhibition has been identified as a novel mechanism of action to address a wide range of disease states, including metabolic disorders, inflammatory diseases, neurodegenerative diseases, and cancer. Artelo is a leader in the development of these lipidome-altering agents, holding worldwide exclusive licenses to multiple FABP inhibitors, with three patents issued in the US and 14 pending patent applications.  Artelo is the first pharmaceutical company to receive FDA approval to initiate human trials with a selective FABP5 inhibitor, named ART26.12.

ART26.12: Lead FABP Inhibitor Compound

ART26.12 is a novel and selective FABP5 inhibitor from Artelo’s proprietary FABP library. In pre-clinical models, ART26.12 demonstrated efficacy in treating Chemotherapy-Induced Peripheral Neuropathy (CIPN), a debilitating complication of cancer therapies often impacting treatment strategies, including stopping treatment altogether. Similar to diabetic neuropathy, CIPN can cause intense and debilitating pain in hands and feet. There is no FDA approved treatment for CIPN.

By deciphering the language of lipids, Artelo Biosciences is on a mission to unlock transformative and novel treatments using lipid-signaling modulation to improve the lives of patients suffering from multiple diseases.

1. Smathers, R.L., Petersen, D.R. The human fatty acid-binding protein family: Evolutionary divergences and functions. Hum Genomics 5, 170 (2011). https://doi.org/10.1186/1479-7364-5-3-170