Evidence map›Paper›PMID 40914167›Full record

ArticleCell reports. Medicine2025

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

Songnan Wang, Randolph M Johnson, Jacqueline A Carozza, Daniel Fernandez, Jan Scicinski, Neil A Verity, Rachel Mardjuki, Xujun Cao, Yingjie Guo, Jacqueline Papkoff and 2 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell reports. Medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed.

  1. Review
  2. Article
  3. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

12 authors.

Songnan WangDepartment of Biochemistry, Stanford University, Stanford, CA 94305, USA; ChEM-H Institute, Stanford University, Stanford, CA 94305, USA; Arc Institute, Palo Alto, CA 94304, USA.
Randolph M JohnsonDepartment of Research and Development, Angarus Therapeutics, Inc., Portola Valley, CA 94028, USA.
Jacqueline A CarozzaArc Institute, Palo Alto, CA 94304, USA.
Daniel FernandezMacromolecular Structure Group, Nucleus at ChEM-H, Stanford University, Stanford, CA 94305, USA.
Jan ScicinskiDepartment of Research and Development, Angarus Therapeutics, Inc., Portola Valley, CA 94028, USA.
Neil A VerityDepartment of Research and Development, Angarus Therapeutics, Inc., Portola Valley, CA 94028, USA.
Rachel MardjukiArc Institute, Palo Alto, CA 94304, USA.
Xujun CaoChEM-H Institute, Stanford University, Stanford, CA 94305, USA; Arc Institute, Palo Alto, CA 94304, USA; Department of Chemistry, Stanford University, Stanford, CA 94305, USA.
Yingjie GuoArc Institute, Palo Alto, CA 94304, USA.
Jacqueline PapkoffDepartment of Research and Development, Angarus Therapeutics, Inc., Portola Valley, CA 94028, USA.
Nigel RayDepartment of Research and Development, Angarus Therapeutics, Inc., Portola Valley, CA 94028, USA.
Lingyin LiDepartment of Biochemistry, Stanford University, Stanford, CA 94305, USA; ChEM-H Institute, Stanford University, Stanford, CA 94305, USA; Arc Institute, Palo Alto, CA 94304, USA. Electronic address: lingyinl@stanford.edu.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Only one in five patients respond to immune checkpoint inhibitors, which primarily target adaptive immunity. Ectonucleotide pyrophosphatase/phophodiesterase 1 (ENPP1), the dominant hydrolase of 2'3'-cyclic-GMP-AMP (cGAMP) that suppresses downstream stimulator of interferon genes (STING) signaling, has emerged as a promising innate immunotherapy 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 systemic clearance, enabled by its high ENPP1 binding affinity and slow dissociation rate. We show that membrane-bound ENPP1 on tumor cells, not the abundant soluble ENPP1 in serum, drives tumor progression. Consequently, STF-1623 unleashes anti-tumor immunity to produce robust anti-tumor and anti-metastatic effects across multiple tumor models. Conceptually, this work establishes a noncovalent small-molecule inhibitor of ENPP1 with ultralong drug-target engagement as a safe and precise strategy to activate STING within tumors.

Indexed as

Immune Checkpoint InhibitorsImmunity, InnateNeoplasmsPhosphoric Diester HydrolasesPyrophosphatasesAnimalsCell Line, TumorFemaleHumansImmunotherapyMiceMice, Inbred C57BLectonucleotide pyrophosphatase phosphodiesterase 1Immune Checkpoint InhibitorsPhosphoric Diester HydrolasesPyrophosphatasesbreast cancercolorectal cancerglioblastomaimmunotransmitterpancreatic cancerSTING agonist

Identifiers

PMID40914167
PMCPMC12490234

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.