MV-658 (Enpp-1-IN-1) - ENPP1 Inhibitor

InvitroFit™ PRR inhibitor

ABOUT

ENPP1 inhibitor for cGAMP-STING-IFN pathway activation

MV-658 (Enpp-1-IN-1) is a potent small-molecule inhibitor of the ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1)1. ENPP1 is an extracellular cell surface-bound enzyme involved in extracellular nucleotide metabolism. It acts as a key negative regulator of antitumor immunity by degrading extracellular 2′3′-cGAMP, an endogenous agonist of the STING pathway. Thereby, ENPP1 dampens STING-mediated innate immune responses and type I interferon production.

MV-658 selectively blocks ENPP1 activity and prevents the degradation of key nucleotide ligands, such as 2′3′-cGAMP. Because STING signaling plays a central role in antitumor immunity, ENPP1 has emerged as an attractive therapeutic target in oncology. Several ENPP1 inhibitors are under investigation for the treatment of solid tumors.

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Key features

  • Potent and selective ENPP1 inhibitor
  • Enhances cGAMP-mediated STING signaling
  • InvitroFit™ grade: each lot is highly pure (≥95%) and functionally tested

 

MV-658 inhibits ENPP1 activity, thereby enhancing STING-dependent IRF signaling, as verified using HepG2-Dual™ cells (see figure). This human hepatocellular carcinoma-derived reporter cell line expresses high levels of ENPP1 on the cell surface (see figure) and features an NF-κB-inducible SEAP and an IRF-inducible Lucia® luciferase reporter protein. Upon co-incubation with MV-658 and the STING agonist 2′3′-cGAMP, MV-658 prevents ENPP1-mediated degradation of 2′3′-cGAMP, resulting in enhanced STING-dependent IRF signaling. The increase in IRF activation is quantitatively measured by assessing Lucia® activity in the cell supernatant, using QUANTI-Luc™ 4 Lucia/Gaussia, a Lucia® luciferase detection reagent.
 

1. William Michael Gallatin, et al. 2018. Ectonucleotide pyrophosphatase-phosphodiesterase 1 (enpp-1) inhibitors and uses thereof. WO2019046778.

All products are for research use only, and not for human or veterinary use.

ENPP1 inhibition by MV-658
ENPP1 inhibition by MV-658

InvitroFit™

InvitroFit™ is a high-quality standard specifically adapted for in vitro studies of inhibitors. InvitroFit™ products are guaranteed free of bacterial contamination, as confirmed using HEK Blue™ TLR2 and HEK Blue™ TLR4 cellular assays. Each lot is rigorously tested for functional activity using validated (or proprietary) cellular models. This grade ensures reliability and reproducibility for your research applications.

SPECIFICATIONS

Specifications

Source
Synthetic
Synonyms
Enpp1-IN-1
MV 658
UUN28589
N-[[4-(7-methoxy-4-quinolinyl)phenyl]methyl]-sulfamide
Target

ENPP1

CAS number
2289728-58-9
Chemical formula

C17H17N3O3S

Molecular weight
343.40 g/mol
Purity
≥ 95% (UHPLC)
Solubility

5 mg/ml in DMSO (14.56 mM) 

Appearance (form)
Dried
Reconstitution buffer
DMSO (not provided)
Working concentration

1.7 - 45 µM for cellular assays

Endotoxin

Negative (tested using EndotoxDetect™ assay)

Tested applications

Cellular assays

Applications

ENPP1 inhibition

Immune modulation

Indirect cGAS-STING inhibition

Quality control

Each lot is functionally tested and validated using cellular assays.

Additional information

Prepare further dilutions in culture media.

CONTENTS

Contents

  • Product: 
    MV-658
  • Cat code: 
    inh-mv658
  • Quantity: 
    1 mg

Shipping & Storage

  • Shipping method:  Room temperature

    • Storage:

    • -20°C
    Stability: Resuspended product is stable for 5 months at -20°C.

    Caution:

    • Avoid repeated freeze-thaw cycles

Details

ENPP1

ENPP1 (Ectonucleotide pyrophosphatase/phosphodiesterase 1) is a cell surface-bound type II transmembrane glycoprotein and the main degrader of the dinucleotide 2′3′-cGAMP (cyclic-GMP-AMP)1-3. cGAMP is synthesized by the enzyme cGAS (cGAMP synthase) following the detection of cytosolic double-stranded (ds)DNA, which arises from chromosomal instability, a hallmark of human cancer. This potent immune-stimulatory molecule then binds and activates STING (stimulator of interferon genes), leading to production of type I interferons (IFN) and downstream immune cell infiltration1. By degrading extracellular cGAMP, ENPP1 functions as an important negative regulator of the cGAMP-STING pathway, limiting T cell infiltration and fostering an immunosuppressive tumor microenvironment that promotes tumor progression and metastasis1-3. Targeting ENPP1 has enormous potential as a novel approach to enhance cGAS-STING-IFN signaling and boost tumor immunity. ENPP1 blockage may therefore function as a novel innate immune checkpoint, offering significant potential for the development of new therapeutics aimed at restoring effective immune surveillance3.

Several ENPP1 inhibitors have progressed into clinical development, highlighting the growing interest in this target for cancer immunotherapy. ISM5939, RBS2418, SR-8541A, and TXN10128 are small-molecule ENPP1 inhibitors currently in Phase 1 or Phase 2 clinical trials, primarily in patients with advanced or metastatic solid cancers2.

 

References:

1. Wang S, et al., 2023. ENPP1 is an innate immune checkpoint of the anticancer cGAMP-STING pathway in breast cancer. Proc Natl Acad Sci U S A. 120(52):e2313693120. 
2. Pu C, et al., 2025. Oral ENPP1 inhibitor designed using generative AI as next generation STING modulator for solid tumors. Nat Commun. 16(1):4793. 
3. Guan D, et al., 2024. Ecto-nucleotide pyrophosphatase/phosphodiesterase 1 inhibitors: Research progress and prospects. Eur J Med Chem. 267:116211.

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