STF-1623, a novel drug developed by Lingyin Li and her team, works by inhibiting the enzyme ENPP1 on tumor surfaces, preventing the breakdown of cGAMP, which stimulates immune activation.

This mechanism allows cGAMP to accumulate and activate the STING pathway in immune cells, triggering a coordinated attack against cancer cells and transforming 'cold' tumors into 'hot' ones more responsive to immunotherapy.

STF-1623 stays bound to ENPP1 for over 24 hours, thanks to its long-term binding capacity, which enhances its efficacy while minimizing side effects, and it is specifically targeted to tumor sites with high ENPP1 concentration.

Preclinical studies published on September 5, 2025, demonstrated STF-1623's effectiveness in multiple mouse models of breast, pancreatic, colorectal, and glioblastoma cancers, with no observed side effects.

This research marks the first successful tumor-specific targeting of an innate immune checkpoint, offering a new strategy to treat resistant 'cold' tumors that do not respond to current immunotherapies.

Following promising results, STF-1623 is moving toward phase I clinical trials after receiving FDA approval, with the potential to become a new cancer treatment.

The drug's development is supported by the NIH, Arc Institute, and Angarus Therapeutics, and it is designed to work best in combination with other therapies.

The study was conducted by Lingyin Li and colleagues, and published in Cell Reports Medicine, highlighting the innovative approach of targeting innate immunity at tumor sites.

Unlike direct STING agonists, STF-1623 preserves natural cGAMP, which may lead to more controlled and targeted immune activation.