Search by Target Class: Enzyme Targets for Celiac Disease

The strategic prioritization of drug targets by target class can be used to streamline discovery, enabling efficient resource allocation and time-savings in early drug development, as well as a competitive edge given the variable success rates of different target classes. For example, in 2017 it was reported that 35% of approved drugs targeted GPCRs.¹ Prioritization of specific target classes may therefore enable investment optimization in preclinical research.  Here, we used human-centric AI to prioritize enzyme targets for celiac disease.

Celiac disease, an autoimmune disease of the small intestine in around 1% of the global population,² is caused by the ingestion of dietary gluten. Currently, the only effective treatment for this condition is adherence to a strict gluten-free diet, which helps to manage symptoms and prevent further complications.³ Notably, enzymes have gained interest as therapeutic targets due to their role in the pathogenesis of this disease, in addition to being viewed as the most desirable drug targets by pharma.⁴

Causaly’s advanced filtering capabilities allows users to refine results by target class, providing a more granular view of targets for a disease. Using Causaly, 700+ targets for celiac disease were identified from 2,100+ relevant sources, providing an instant view of the entire target landscape.

Around one quarter of the targets identified by Causaly were enzymes, Figure 1. Filtering further by those reported in the last 5 years (2019-2024) revealed that the most studied subclass of enzymes to be hydrolases (45%), transferases (34%) and oxidoreductases (14%).

In this example, we focused on hydrolases as potential targets for celiac disease, uncovering 16 hydrolases reported in primary data. By examining the evidence, ASAH2 was selected for further exploration owing to its potential role in the gut-brain axis of celiac disease patients.⁵

Using the hypothesis generation tool, interfering pathways which may mediate the effect of ASAH2 on celiac disease can be identified.  For example, the enzymatic inhibition or knockout of ASAH2 has shown to promote apoptosis,⁶  a pathway (among others) implicated in celiac disease,⁷ which can form the basis of a hypothesis.

The strategic prioritization of drug targets based on their classification can significantly enhance the efficiency of drug discovery. Focusing on specific target classes facilitates more efficient resource allocation in early drug development, streamlining the identification of more effective treatments.