Scientific Approach

Realizing the Therapeutic Value of Serine Hydrolases

Abide is focused on one of the largest and most diverse enzyme classes in humans – the serine hydrolases. With more than 200 members, serine hydrolases profoundly influence human health by playing vital roles in many physiological and disease processes.

Serine hydrolases influence physiology by controlling the levels of diverse bioactive signaling molecules, including lipids, neurotransmitters, peptides, and proteins involved in important biological processes such as mood, pain perception, and inflammation. Our platform enables the discovery and development of first-in-class serine hydrolase inhibitors that restore the physiological balance of signaling pathways deregulated in human diseases of the central nervous system (CNS) and periphery.

Scientific Approach

Targeting the Endocannabinoid Pathway for a New Class of CNS Drugs

The endocannabinoid system plays a crucial function in maintaining proper activity of the human nervous system and offers a compelling therapeutic target for a wide range of CNS diseases. Selective inhibition of the serine hydrolase monoacylglycerol lipase (MGLL) can potentiate endocannabinoid signaling to counteract disease states and restore homeostatic balance in the CNS. Abide’s lead product candidate, ABX-1431, is a first-in-class MGLL inhibitor that modulates the endocannabinoid system preferentially in areas where neuronal circuits are excessively activated. We are developing ABX-1431 and two other MGLL inhibitors with the potential to treat a broad range of CNS diseases.

Abide has created a first-in-class product candidate and advanced it to Phase 2 development, with three additional compounds poised to enter the clinic and multiple promising new targets under evaluation.

Unique Serine Hydrolase Inhibitor Platform

Our innovative platform delivers highly selective molecules that target serine hydrolases. The three key components of our platform are a proprietary chemical library with highly enriched activity against serine hydrolases; an activity-based protein profiling (ABPP) assay technology that can be universally applied to any human serine hydrolase; and metabolomics methods that enable rapid and comprehensive understanding of serine hydrolase substrates and products in physiological and disease states. Through our effective integration of these components, we can identify and validate novel serine hydrolase targets and rapidly develop potent and selective small-molecule inhibitors for advancement into the clinic.

Our chemical library consists of more than 20,000 compounds designed specifically to inhibit serine hydrolases. The library has already furnished inhibitors for ~80% of the more than 200 human serine hydrolases and continually evolves as new targets are characterized and new leads identified.

The ABPP technology, pioneered by our co-founder Dr. Benjamin Cravatt and colleagues at Scripps, serves as a universal assay for screening small molecules from our library against the entire serine hydrolase family, efficiently evaluating inhibitor potency and selectivity in one step.

We also use metabolomics to measure the effects of inhibitors on substrates and products of serine hydrolases in target tissues. This in vivo confirmation of activity provides a deep understanding of inhibitor potency and target engagement, accelerating preclinical discovery and facilitating biomarker development to confirm biological effect and appropriate dosing.

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Using our powerful platform, Abide is able to:

Scientific Publications and Presentations