Gentiopicroside Study

(Chicago, Illinois) February 19, 2026

ExoMira Medicine Inc. is spotlighting a key peer-reviewed publication co-authored by ExoMira scientific co-founder Dr. Deyu Fang that strengthens the scientific case for USP22 inhibition as a differentiated, next-generation cancer immunotherapy strategy. In Biomedicine & Pharmacotherapy, the team reports that gentiopicroside—a natural secoiridoid glycoside—acts as a USP22 inhibitor and enhances antitumor immunity through multiple converging lines of evidence. 

A Natural-Product Clue, a First-in-Class Path: Why USP22 Is a Promising Immunotherapy Target

This study is compelling because it doesn’t rely on a single readout; it triangulates USP22 inhibition across Treg biology, tumor checkpoint regulation, and structural binding evidence, then links these to functional antitumor immunity in vivo:

• Direct impact on Tregs (FOXP3 axis): Gentiopicroside suppresses Foxp3 protein expression in a human Treg cell line and in mouse Tregs in vivo—consistent with weakening Treg-mediated immunosuppression in the tumor microenvironment. 

• On-target USP22 pathway engagement (H2Bub): Treatment increases H2B monoubiquitination (H2Bub) in a USP22-dependent manner, supporting that the mechanism tracks with USP22 catalytic function rather than broad, nonspecific effects. 

• Checkpoint modulation (PD-L1): The work reports reduced tumor cell surface PD-L1, attributed to enhanced ubiquitination and proteasomal degradation—an immunologically meaningful lever given PD-1/PD-L1’s central role in immune evasion. 

• Structural plausibility: Docking and molecular dynamics simulations indicate stable binding in the USP22 catalytic pocket, reinforcing a coherent structure-mechanism narrative. 

• Functional immunity and tumor control: In mice, gentiopicroside administration increases CD8⁺ T-cell effector output (including IFN-γ and GZMB) and inhibits tumor growth—connecting mechanism to meaningful antitumor activity. 

Why this is especially timely in the post-Nobel Treg era

The 2025 Nobel Prize in Physiology or Medicine recognized discoveries underpinning regulatory T cells (Tregs) and immune tolerance, highlighting both the promise and complexity of modulating immune “brakes” in human disease. 

For cancer, the opportunity is clear: intratumoral Tregs can suppress effective antitumor immunity. The challenge is equally clear: many approaches that broadly suppress immune regulation can create safety liabilities. ExoMira’s focus is to translate validated Treg biology into precise, druggable mechanisms that aim to boost antitumor immunity while maintaining a responsible therapeutic window.

How this reinforces ExoMira’s product strategy for MIRA-1

The gentiopicroside study provides independent, founder-led validation of a core ExoMira belief: USP22 sits at a strategic intersection of tumor immune evasion and Treg-driven suppression—enabling a potential “dual-action” immunotherapy effect (Treg fitness + checkpoint biology). 

Importantly, the authors also note that as a natural product, gentiopicroside’s antitumor activity is modest, but it serves as a credible lead and rationale for engineering more potent, development-ready USP22 inhibitors. That is exactly where ExoMira’s flagship program, MIRA-1, is positioned: a first-in-class small-molecule USP22 inhibitor being advanced through IND-enabling studies with a rigorous focus on mechanism, efficacy, and safety signals.