ENPP1 inhibitor with ultralong drug-target residence time as an innate immune checkpoint blockade cancer therapy.

ABSTRACT: Only one in five patients is estimated to respond to immune checkpoint inhibitors, which primarily target adaptive immunity. To date, no FDA-approved immunotherapies directly activate the innate anti-cancer immunity-an essential driver of lymphocyte recruitment and potentiator of responses to existing cancer immunotherapies. ENPP1, the dominant hydrolase that degrades extracellular cGAMP and suppresses downstream STING-mediated innate immune signaling, has emerged as a promising therapeutic target. However, existing ENPP1 inhibitors have been optimized for prolonged systemic residence time rather than effective target inhibition within tumors. Here, we report the characterization of STF-1623, a highly potent ENPP1 inhibitor with an exceptionally long tumor residence time despite rapid syst

SUBMITTER: Johnson RM 

PROVIDER: S-EPMC12139726 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature