Evidence map›Paper›PMID 32726585›Full record

ArticleCell chemical biology2020

Structure-Aided Development of Small-Molecule Inhibitors of ENPP1, the Extracellular Phosphodiesterase of the Immunotransmitter cGAMP.

Jacqueline A Carozza, Jenifer A Brown, Volker Böhnert, Daniel Fernandez, Yasmeen AlSaif, Rachel E Mardjuki, Mark Smith, Lingyin Li

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell chemical biology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers.

0numbers the graph read from it
0cells of the map it votes in
60citing papers in PubMed
4.4field-weighted citation impact, top 4% of its field
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

60 citing papers in PubMed, 104 citations in OpenAlex.

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  10. Conjugated STING agonists.Molecular therapy. Nucleic acids · 2025
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

8 authors at 2 institutions in 1 country.

Jacqueline A CarozzaDepartment of Chemistry, Stanford University, Stanford, CA 93405, USA; Stanford ChEM-H, Stanford University, Stanford, CA 93405, USA.
Jenifer A BrownStanford ChEM-H, Stanford University, Stanford, CA 93405, USA; Biophysics Program, Stanford University, Stanford, CA 93405, USA.
Volker BöhnertStanford ChEM-H, Stanford University, Stanford, CA 93405, USA; Department of Biochemistry, Stanford University, Stanford, CA 93405, USA.
Daniel FernandezStanford ChEM-H Macromolecular Structure Knowledge Center, Stanford University, Stanford, CA 93405, USA.
Yasmeen AlSaifStanford ChEM-H, Stanford University, Stanford, CA 93405, USA; Department of Biology, Stanford University, Stanford, CA 93405, USA.
Rachel E MardjukiDepartment of Chemistry, Stanford University, Stanford, CA 93405, USA; Stanford ChEM-H, Stanford University, Stanford, CA 93405, USA.
Mark SmithStanford ChEM-H Medicinal Chemistry Knowledge Center, Stanford, CA 93405, USA.
Lingyin LiStanford ChEM-H, Stanford University, Stanford, CA 93405, USA; Department of Biochemistry, Stanford University, Stanford, CA 93405, USA. Electronic address: lingyinl@stanford.edu.
Stanford University · USStanford Medicine · US

Funding

Chemical biology of innate immunity for treating cancer and autoimmunityDP2CA228044 · NCI · STANFORD UNIVERSITY · PI LI, LINGYIN · 2017 to 2017
$2.4M
Harnessing the innate immunotransmitter cGAMP for anti-cancer therapyF31CA239510 · NCI · STANFORD UNIVERSITY · PI CAROZZA, JACQUELINE · 2019 to 2021
$104k
NCI NIH HHS DP2 CA228044NCI NIH HHS F31 CA239510
6 · The paper itself

Abstract

Cancer cells initiate an innate immune response by synthesizing and exporting the small-molecule immunotransmitter cGAMP, which activates the anti-cancer Stimulator of Interferon Genes (STING) pathway in the host. An extracellular enzyme, ectonucleotide pyrophosphatase phosphodiesterase 1 (ENPP1), hydrolyzes cGAMP and negatively regulates this anti-cancer immune response. Small-molecule ENPP1 inhibitors are much needed as tools to study the basic biology of extracellular cGAMP and as investigational cancer immunotherapy drugs. Here, we surveyed structure-activity relationships around a series of cell-impermeable and thus extracellular-targeting phosphonate inhibitors of ENPP1. In addition, we solved the crystal structure of an exemplary phosphonate inhibitor to elucidate the interactions that drive potency. This study yielded several best-in-class inhibitors with K

Indexed as

AnimalsAntineoplastic AgentsCells, CulturedCell SurvivalDose-Response Relationship, DrugDrug Screening Assays, AntitumorEnzyme InhibitorsFemaleHumansMiceMice, Inbred C57BLMolecular StructureNeoplasms, ExperimentalNeurotransmitter AgentsNucleotides, CyclicPhosphoric Diester HydrolasesAntineoplastic Agentscyclic guanosine monophosphate-adenosine monophosphateectonucleotide pyrophosphatase phosphodiesterase 1Enzyme InhibitorsNeurotransmitter AgentsNucleotides, CyclicPhosphoric Diester HydrolasesPyrophosphatasesSmall Molecule Libraries2′3′-cGAMPcancer immunotherapycrystal structureENPP1extracellular signalingimmunotransmittersmall-molecule inhibitorsSTINGstructure-aided design

Identifiers

PMID32726585
PMCPMC7680421
OpenAlexW3045982690

What OpenQuestion holds

Textmetadata
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Read underepoch 390

Registered trials

None linked

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.