Scripps Research Scientists Develop ENDOtollins to Neutralize Autoimmune Inflammation While Preserving Essential Viral Immunity

Scripps Research scientists unveil ENDOtollins, a drug class that stops autoimmune inflammation while keeping the body's viral defenses fully intact.

By: AXL Media

Published: Apr 7, 2026, 6:49 AM EDT

Source: Information for this report was sourced from Scripps Research Institute and Nature Chemical Biology.

Precision Targeting of Molecular Handshakes in Immune Cells

A breakthrough in pharmacological research has led to the creation of ENDOtollins, a drug class designed to interrupt specific protein interactions that drive autoimmune disease. Scientists at Scripps Research focused on the binding process between two proteins, Munc13-4 and syntaxin 7, which acts as a mechanical trigger for Toll-like receptors within cell compartments. By blocking this specific "molecular handshake," the compounds prevent immune sensors from erroneously attacking the body's own genetic material. According to senior author Sergio D. Catz, understanding these precise biological mechanisms allows for the suppression of inflammatory pathways while leaving other critical cellular processes undisturbed.

Overcoming the Side Effects of Conventional Autoimmune Care

Current standards of care for the 15 million Americans suffering from autoimmune disorders often rely on broad-spectrum medications like hydroxychloroquine. While these treatments are effective, they work by generally blocking cell endosomes, which frequently results in gastrointestinal distress and potential long-term vision damage. These systemic side effects often force patients to abandon their treatment regimens. The development of ENDOtollins represents a shift toward more refined therapy, as these molecules specifically target Munc13-4, a protein primarily found within immune cells. This selectivity ensures that the drug's impact is localized to the source of the inflammation rather than affecting the entire body.

Innovative Screening in Intact Cellular Environments

The discovery process involved an exhaustive screen of approximately 32,000 compounds conducted at the Scripps Research Molecular Screening Center. Unlike traditional drug discovery methods that analyze isolated proteins, the team utilized an innovative approach that kept cellular compartments fully intact during testing. Jennifer Johnson, the study’s first author, noted that maintaining proteins in their natural environment significantly increases the probability that the identified compounds will remain effective in living organisms. This methodological choice was instrumental in identifying ENDO12, the most potent compound in the new class, which demonstrated high efficacy in animal models.