enpp1  (MedChemExpress)

Journal: Nature Communications

Article Title: Oral ENPP1 inhibitor designed using generative AI as next generation STING modulator for solid tumors

doi: 10.1038/s41467-025-59874-0

Figure Lengend Snippet: A Indication prioritization tools embedded in PandaOmics to rank indications for ENPP1. B The correlation analysis of type-I IFN related immune parameters across cancer types: Correlation between ENPP1 expression in tumor cells and ISG score in conventional dendritic cells (cDC) in gastric cancer (OMIX001073, n = 10) and colorectal cancer (CRC, GSE132465 , n = 23), as well as correlation between ENPP1 expression in tumor cells and CXCL10 expression in dendritic cells (DC) and cDC percentage in triple-negative breast cancer (TNBC, GSE176078 , n = 10). Each dot represents a single patient sample. The x-axis indicates the ENPP1 expression in tumor cells and the y-axis displays the corresponding immune parameters: ISG score, CXCL10 expression or cDC percentage. The P value and correlation were performed using Pearson’s correlation coefficient, with the resulting trend line depicted in blue. The gray shaded area surrounding the trend line represents the 95% confidence intervals. Source data are provided as a Source Data file. C Spatial distribution of ENPP1, ISG score and predicted proportion of CD8 T and pro-inflammatory macrophage cells per spot in histology slide SN84_A120838_Rep2 from CRC patient (Zenodo record: 7760264). The color represents the value of ENPP1 expression, ISG score and predicted proportion of DC and NK cells per spot. Source data are provided as a Source Data file. D Spatial distribution of ENPP1, ISG score and predicted proportion of CD4 T and DC cells per spots in slide GSM6433591_094A from a TNBC patient (GEO: GSE210616 ). The color represents the value of ENPP1 expression, ISG score and predicted proportion of DC and NK cells per spot. Source data are provided as a Source Data file. E Spatial distribution of ENPP1, ISG score and predicted proportion of DC and NK cells per spot in slide 21_00734_LI_SING from a GC patient (GEO: GSE251950 ). The color represents the value of ENPP1 expression, ISG score and predicted proportion of DC and NK cells per spot. Source data are provided as a Source Data file.

Article Snippet: So far, no ENPP1 inhibitors have been approved for clinical use, but three have progressed to clinical trials, including RBS2418 (Riboscience), TXN10128 (Txinno Bioscience), and SR-8541A (Stingray Therapeutics).

Techniques: Expressing

Journal: Nature Communications

Article Title: Oral ENPP1 inhibitor designed using generative AI as next generation STING modulator for solid tumors

doi: 10.1038/s41467-025-59874-0

Figure Lengend Snippet: A Flow scheme for AI-facilitated ENPP1 inhibitor discovery. ReRSA, retrosynthesis related synthetic accessibility; SA, synthetic accessibility; PXR, pregnane xenobiotic receptor. Novelty calculated based on the dataset compiled from ChEMBL. Alchemistry, accurately estimates the relative binding free energy to prioritize molecules with efficient physics-based methods. ADMET prediction, predict physicochemical and ADMET molecular properties. B Docking pose of ISM7516 with human ENPP1. The source data are provided as a Source Data file. ENPP1 (white) is shown in ribbon and ISM7516 (cyan) is drawn in sphere, while key residues (white) and ISM7516(cyan) are shown in stick. C Docking pose of ISM5939 with human ENPP1. The source data are provided as a Source Data file. ISM5939 (yellow) was superimposed with AMP (purple, PDB ID: 6wfj) and QPS2 (green, PDB ID: 6wev). Zn atoms are shown as gray sphere and dashed lines indicate hydrogen bonds or coordination bonds. D Biochemical/cellular activity, △G cal , CYP3A4 induction, hERG inhibition and predicted hERG inhibition value of candidate inhibitors. The data are colored by profiling results. Green represents ideal profiling, orange indicates potential issues, black represents acceptable results, and red represents unacceptable outcomes. CYP3A4 induction calculated as ratio of CYP3A4 mRNA following compound treatment at 10 µM compared to rifampicin. △G cal was calculated by Alchemistry tool. hERG, human ether-a-go-go-related gene. Predicted hERG inhibition values were achieved by ADMET prediction module.

Article Snippet: So far, no ENPP1 inhibitors have been approved for clinical use, but three have progressed to clinical trials, including RBS2418 (Riboscience), TXN10128 (Txinno Bioscience), and SR-8541A (Stingray Therapeutics).

Techniques: Binding Assay, Activity Assay, Inhibition

Journal: Nature Communications

Article Title: Oral ENPP1 inhibitor designed using generative AI as next generation STING modulator for solid tumors

doi: 10.1038/s41467-025-59874-0

Figure Lengend Snippet: A Concentration response curves of ISM5939 or positive control (ENPP-1-IN-1) in ENPP1 enzymatic assay (pH 7.4, n = 2 biological replicates, 2 independent experiments). Left, 2,3- cGAMP as substrate; right, ATP as substrate. B IC 50 values for ISM5939 against human ENPP1 catalytic activity using 2’,3’ cGAMP or ATP as substrates at pH 7.4 and pH 6.5. C Concentration response curves of ISM5939 in the ENPP1 enzymatic assay at different concentrations of ATP and cGAMP ( n = 2 biological replicates). D – F The inhibitory activity of ISM5939 against the catalytic activity of (D) human ENPP2 (E) human ENPP3 and (F) table summary for IC 50 values ( n = 2 biological replicates). G The Rador map illustrating the effect of ISM5939 (10 μM) on SafetyOne44 Panel targets ( n = 2 biological replicates). H Inhibitory effects of ISM5939 on cGAMP degradation mediated by soluble ENPP1 in human plasma detected by ELISA. I Stabilization of cGAMP in vivo in murine plasma by ISM5939 ( n = 3 biological replicates). Data were analyzed by two‐tailed, unpaired Student’s t‐test. P-value < 0.05 were shown. J Potency of ISM5939 in maintaining extracellular cGAMP levels when applied to cancer cells in vitro ( n = 2 biological replicates). Data were represented as mean ± SEM. Source data are provided as a Source Data file.

Article Snippet: So far, no ENPP1 inhibitors have been approved for clinical use, but three have progressed to clinical trials, including RBS2418 (Riboscience), TXN10128 (Txinno Bioscience), and SR-8541A (Stingray Therapeutics).

Techniques: Concentration Assay, Positive Control, Enzymatic Assay, Activity Assay, Clinical Proteomics, Enzyme-linked Immunosorbent Assay, In Vivo, Two Tailed Test, In Vitro

Journal: Nature Communications

Article Title: Oral ENPP1 inhibitor designed using generative AI as next generation STING modulator for solid tumors

doi: 10.1038/s41467-025-59874-0

Figure Lengend Snippet: A Baseline ENPP1 expression levels in Paclitaxel+anti-PD1 responsive or non-responsive breast cancer patients (GEO: GSE194040 ). n = 38 for responders and n = 31 for non-responders. B Baseline ENPP1 expression levels in anti-PD-L1 responsive or non-responsive esophageal adenocarcinoma patients with high LRRC8A expression. Data were extracted from GSE165252 . n = 6 for responders and n = 3 for non-responders. For boxplots, boxes indicate 25th and 75th percentiles, the lines within boxes mark medians, whiskers extend over 1.5 times the interquartile range (IQR, the distance from 25th to 75th percentile); dots represent patient samples. C Combinational effect of ISM5939 and anti-PD-L1 therapy. MC38 tumor‐bearing C57BL/6 J mice were treated with anti‐PD‐L1 antibody (3 mg kg −1 , twice per week) alone or in combination with ISM5939 (30 mg/kg, twice a day) for indicated days ( n = 6 biological replicates per group). D Combinational effect of ISM5939 and anti-PD1 therapy. MC38 tumor‐bearing C57BL/6 J mice were treated with anti‐PD1 antibody (5 mg kg −1 , twice per week) alone or in combination with ISM5939 at the indicated doses ( n = 8 biological replicates per group). E – H Tumor infiltrating immune cells analyzed by flow cytometry. MC38 tumor‐bearing C57BL/6 J mice were treated with anti‐PD1 antibody (5 mg kg −1 , twice per week) alone or in combination with ISM5939 (20 mg kg −1 , twice a day) for 7 consecutive days ( n = 6 biological replicates). E, F The proportion of the indicated immune cells in tumor infiltrating CD45 + cells; G The ratio of CD8 + T cells (left) and CD4 + T cells (right) to Tregs. H CD69 positive ratios among the indicated immune subsets. I Tumor growth of CT26 syngeneic tumors. Tumor bearing mice ( n = 6 biological replicates per group) were treated with anti-PD1 antibody alone or in combination with ISM5939 (20 mg kg −1 , twice a day). Data are represented as mean ± SEM. For ( A , B ) and ( E – G ), data were analyzed by two‐tailed Student’s t‐test. P value < 0.05 were shown. Data were represented as mean ± SEM. Source data are provided as a Source Data file.

Article Snippet: So far, no ENPP1 inhibitors have been approved for clinical use, but three have progressed to clinical trials, including RBS2418 (Riboscience), TXN10128 (Txinno Bioscience), and SR-8541A (Stingray Therapeutics).

Techniques: Expressing, Flow Cytometry, Two Tailed Test

Journal: Nature Communications

Article Title: Oral ENPP1 inhibitor designed using generative AI as next generation STING modulator for solid tumors

doi: 10.1038/s41467-025-59874-0

Figure Lengend Snippet: A Baseline ENPP1 expression levels in chemotherapy responsive or non-responsive TNBC, HER2 positive breast cancer, ER positive breast cancer and colorectal cancer patients. Data were extracted from GSE22513 , GSE50948 , GSE22093 and GSE28702 . For TNBC, n = 8 for responders and n = 20 for non-responders; for HER2 positive breast cancer, n = 22 for responders and n = 71 for non-responders; for ER positive breast cancer, n = 10 for responders and n = 32 for non-responders; for CRC, n = 42 for responders and n = 41 for non-responders. For boxplots, boxes indicate 25th and 75th percentiles, the lines within boxes mark medians, whiskers extend over 1.5 times the interquartile range (IQR, the distance from 25th to 75th percentile); dots represent patient samples. B Maximal cGAMP release induced by combined use of cisplatin or paclitaxel with ISM5939 ( n = 2 biological replicates, two independent experiments). C – E EMT6 syngeneic tumor bearing mice treated with cisplatin and ISM5939 alone or in combination for 2 weeks to profile ( C ) differential tumor growth and ( D , E ) endpoint tumor sample bulk RNA sequencing showing ( D ) pathway enrichment (The color represents adjust P-value) and ( E ) deconvoluted immune cell populations in the tumor microenvironment post-treatment ( n = 6 biological replicates for tumor growth detection, n = 3 biological replicates for RNA sequencing). Color represents z-scores of cell population, values range from red (low population) to green (high population). F Tumor growth of 4T1 orthotopic tumor-bearing mice treated with docetaxel and ISM5939 alone or in combination. G In vitro release of cGAMP by BRCA-proficient (MDA-MB-231, ID8) or BRCA-deficient (MDA-MB-436, UWB1.289) cells treated with Olaparib or ISM5939 alone or in combination via ELISA ( n = 2 biological replicates). H Tumor growth of 4T1 orthotopic tumor-bearing mice treated with Olaparib and ISM5939 alone or in combination ( n = 7 biological replicates). Data were represented as mean ± SEM. For ( A ), ( C ), ( F ) and ( H ), data were analyzed by two‐tailed Student’s t‐test. P value < 0.05 were shown. Source data are provided as a Source Data file.

Article Snippet: So far, no ENPP1 inhibitors have been approved for clinical use, but three have progressed to clinical trials, including RBS2418 (Riboscience), TXN10128 (Txinno Bioscience), and SR-8541A (Stingray Therapeutics).

Techniques: Expressing, RNA Sequencing, In Vitro, Enzyme-linked Immunosorbent Assay, Two Tailed Test

Journal: Nature Communications

Article Title: Oral ENPP1 inhibitor designed using generative AI as next generation STING modulator for solid tumors

doi: 10.1038/s41467-025-59874-0

Figure Lengend Snippet: ISM5939 facilitates the accumulation of extracellular cGAMP by blocking ENPP1-dependent degradation, thereby triggering the cGAS-STING signaling pathway in antigen-presenting cells (APCs). This activation effectively enhances the activity of CD8 + T cells. Additionally, ISM5939 diminishes adenosine production by inhibiting ENPP1-mediated ATP hydrolysis, potentially mitigating the suppression of tumor-infiltrating T cells.

Article Snippet: So far, no ENPP1 inhibitors have been approved for clinical use, but three have progressed to clinical trials, including RBS2418 (Riboscience), TXN10128 (Txinno Bioscience), and SR-8541A (Stingray Therapeutics).

Techniques: Blocking Assay, Activation Assay, Activity Assay

Journal: iScience

Article Title: DNA-PK inhibition sustains the antitumor innate immune response in small cell lung cancer

doi: 10.1016/j.isci.2025.111943

Figure Lengend Snippet:

Article Snippet: Enpp-1-IN-1 (UUN28589, MV 658), ENPP1 inhibitor , Selleck Chemicals , Cat#S0501.

Techniques: Activation Assay, Recombinant, MTS Assay, CyQUANT Assay, LDH Cytotoxicity Assay, cDNA Synthesis, Control, Software, Microscopy, Spectrophotometry

Journal: Neuro-Oncology

Article Title: ENPP1 induces blood–brain barrier dysfunction and promotes brain metastasis formation in human epidermal growth factor receptor 2-positive breast cancer

doi: 10.1093/neuonc/noae169

Figure Lengend Snippet: Proteomic analysis identifies ENPP1 as a brain metastatic protein. (A) List of total proteins and differentially expressed proteins (DEPs) between the 2 pairwise comparison groups JIMT-1-BR versus JIMT-1 and SUM190-BR versus SUM190 cells. (B) Principal component and (C) unsupervised hierarchical clustering analysis of the SCR from breast cancer (BC) cell lines. (D) Venn diagram illustrating the overlap of DEPs identified in both comparisons, revealing common proteins in the SCR of brain-tropic cells. (E) Gene ontology analysis encompassing cellular components, biological process, and molecular functions, along with Reactome pathway enrichment analysis output of the 35 common DEPs between the 2 pairwise comparison groups. Numbers of involved proteins are indicated by the left y -axis and displayed as bars; P -values (as −Log10 values) are indicated by the right y -axis and displayed in dots. (F) Heatmap of protein abundance expression of the 35 common DEPs in BC cell lines.

Article Snippet: Additionally, ENPP1 Inhibitor 4e (ENPP1i; Cayman Chemical; CAY-37687) was added at 10 μM during incubation with brain-tropic cell SCR for 24 hours.

Techniques: Comparison, Quantitative Proteomics, Expressing

Journal: Neuro-Oncology

Article Title: ENPP1 induces blood–brain barrier dysfunction and promotes brain metastasis formation in human epidermal growth factor receptor 2-positive breast cancer

doi: 10.1093/neuonc/noae169

Figure Lengend Snippet: ENPP1 triggers blood-brain barrier (BBB) dysfunction by suppressing the AKT/GSK3β/β-catenin pathway in brain endothelial cells. (A) Representative western blot of ENPP1 expression in breast cancer (BC) cell lysates (top) and SCR (bottom). (B) ELISA analysis of ENPP1 levels in the SCR of BC cells. Statistical significance was assessed using Mann–Whitney test. *** P < .001 compared to JIMT-1-BR cells. ### P < .001 compared to SUM190-BR cells. (C) Scheme illustrating the establishment of a static BBB in vitro model through the co-culture of endothelial cells (ECs) with HBVPs treated with SCR from brain-tropic cells in the absence or presence of the ENPP1 inhibitor (ENPP1i) at 10 µM. The BBB integrity was evaluated by measuring the (D) 4 kDa FITC-dextran permeability and TEER after 24 hours of treatment, n = 4 to 6. (E) Quantification of ZO-1 and β-catenin immunofluorescence and (F) representative confocal images of ZO-1 and β-catenin immunoreactivity in ECs after treatments, n = 4 to 6. (G) Schematic illustration of GFP+ BC cells transmigration through the BBB after exposure to the SCR from BC cells, in the presence or absence of ENPP1i. Quantification and representative images of transendothelial migration (TEM) of BC cells across the BBB, n = 3. Statistical significance was assessed using Mann–Whitney test. #### P < .0001 compared to JIMT-1 cells. $$$$ P < .0001 compared to SUM190 cells. Scale Bar: 100 µm (H) Schematic diagram illustrating the EC dysfunction mediated by ENPP1 by suppressing insulin signaling and downstream AKT/GSK3β/β-catenin pathway. (I) Representative images from western blot analysis of p-INSR, INSR, p-AKT, AKT, p-GSK3β, GSK3β, AXIN2, and β-catenin in ECs upon the treatment with the SCR, in the presence or absence of ENPP1i, n = 4 to 5. GAPDH was used as the loading control and for band density normalization. Statistical significance was assessed using one-way ANOVA followed by Turkey’s multiple comparison test. ** P < .01, **** P < .0001 compared to control ( dashed line ). #### P < .0001 compared to SCR from JIMT-1-BR cells; $$ P < .01, $$$ P < .001 $$$$ P < .0001 compared to SCR from SUM190-BR cells. Nuclei were stained with Hoechst 33342. Scale Bar: 20 µm.

Article Snippet: Additionally, ENPP1 Inhibitor 4e (ENPP1i; Cayman Chemical; CAY-37687) was added at 10 μM during incubation with brain-tropic cell SCR for 24 hours.

Techniques: Western Blot, Expressing, Enzyme-linked Immunosorbent Assay, MANN-WHITNEY, In Vitro, Co-Culture Assay, Permeability, Immunofluorescence, Transmigration Assay, Migration, Control, Comparison, Staining

Journal: Neuro-Oncology

Article Title: ENPP1 induces blood–brain barrier dysfunction and promotes brain metastasis formation in human epidermal growth factor receptor 2-positive breast cancer

doi: 10.1093/neuonc/noae169

Figure Lengend Snippet: ENPP1 knockdown in brain metastatic cells prevents blood-brain barrier (BBB) dysfunction. (A) Representative western blot of ENPP1 expression in wild type (WT), non-targeting siRNA (siNT) and ENPP1 siRNA knockdown (siENPP1) in JIMT-1-BR (left) and SUM190-BR (right) brain metastatic cells. (B) Scheme of the microfluidic-based BBB in vitro model established by the co-culture of endothelial cells (ECs) with HBVPs under flow conditions treated with SCR from parental cells, siENPP1, and siNT brain-tropic cells. The BBB integrity was evaluated by measuring the (C) 4 kDa FITC-dextran permeability, n = 3. (D) Representative confocal images of claudin-5, β-catenin, ZO-1 immunoreactivity. Quantification of immunofluorescence levels of (E) claudin-5, (F) β-catenin, and (G) ZO-1 proteins in ECs. (H) Representative FLI images of in vivo and ex vivo SCR-treated mice acquired at 2h post-injection of 20 kDa Cy7.5-dextran, n = 3 per group. The color scale shows radiant efficiency. (I) Representative confocal images of collagen ІV, albumin, and claudin-5 immunostaining in the brain vessels. Statistical significance was assessed using one-way ANOVA followed by Dunn’s multiple comparison test. * P < .05, ** P < .01, *** P < .001, **** P < .0001 compared to control ( dashed line ). ## P < .01, ### P < .001, #### P < .0001 compared to SCR from siNT JIMT-1-BR cells; $ P < .05, $$ P < .01 $$$ P < .001, $$$$ P < .0001 compared to SCR from siNT SUM190-BR cells. Nuclei were stained with Hoechst 33342. Scale Bar: 20 µm.

Article Snippet: Additionally, ENPP1 Inhibitor 4e (ENPP1i; Cayman Chemical; CAY-37687) was added at 10 μM during incubation with brain-tropic cell SCR for 24 hours.

Techniques: Knockdown, Western Blot, Expressing, In Vitro, Co-Culture Assay, Permeability, Immunofluorescence, In Vivo, Ex Vivo, Injection, Immunostaining, Comparison, Control, Staining

Journal: Neuro-Oncology

Article Title: ENPP1 induces blood–brain barrier dysfunction and promotes brain metastasis formation in human epidermal growth factor receptor 2-positive breast cancer

doi: 10.1093/neuonc/noae169

Figure Lengend Snippet: Primary tumor (PT) disrupts the blood-brain barrier (BBB) through the systemic release of ENPP1. (A) Representative western blot of ENPP1 expression in LOXP (control vector) and ENPP1 knockout (KO) JIMT-1-BR cells. (B) Schematic diagram illustrating the orthotopic injection of JIMT-1-BR (WT and ENPP1-KO) and parental JIMT-1 cells into the mammary fat pad. BBB integrity was assessed by FLI detection when the PT reached a maximum volume of 50–60 mm 3 , n = 3 per group. (C) Representative BLI images of PT 15 days after the implementation of breast cancer (BC) cells. The color scale shows radiance (photons/sec/cm 2 /sr). (D) Volumes of orthotopic primary breast tumors over time. (E) Representative FLI images and (F) quantification of fluorescence in PT-bearing mice in vivo (left) and ex vivo (right) 2 hours post-injection of 20 kDa Cy7.5-dextran. The color scale shows radiant efficiency. (G) Plasma levels of ENPP1 in healthy mice and mice bearing PTs from JIMT-1, WT JIMT-1-BR, and ENPP1-KO JIMT-1-BR cells. (H) Representative immunohistochemical images of ENPP1 expression (top) and histopathological H&E (bottom) in resected PTs. Scale bars: 1 mm (left) and 100 µm (right). Statistical significance was assessed using one-way ANOVA followed by Dunn’s multiple comparison test. * P < .05, ** P < .01, **** P < .0001 compared to WT JIMT-1-BR PT-bearing mice.

Article Snippet: Additionally, ENPP1 Inhibitor 4e (ENPP1i; Cayman Chemical; CAY-37687) was added at 10 μM during incubation with brain-tropic cell SCR for 24 hours.

Techniques: Western Blot, Expressing, Control, Plasmid Preparation, Knock-Out, Injection, Fluorescence, In Vivo, Ex Vivo, Clinical Proteomics, Immunohistochemical staining, Comparison

Journal: Neuro-Oncology

Article Title: ENPP1 induces blood–brain barrier dysfunction and promotes brain metastasis formation in human epidermal growth factor receptor 2-positive breast cancer

doi: 10.1093/neuonc/noae169

Figure Lengend Snippet: ENPP1 knockout decreases the metastatic potential of brain metastatic cells. (A) Scheme of the experimental model of BrM established by intracardiac injection of parental JIMT-1 ( n = 3) and JIMT-1-BR WT ( n = 6), LOXP-KO ( n = 6), and ENPP1-KO ( n = 9) cells into the left ventricle. (B) Representative BLI images of experimental BrM formation over time post-intracardiac injection of breast cancer (BC) cells. The color scale shows radiance (photons/sec/cm 2 /sr) (C) Quantification of BLI signal intensities over time (fold change from day 0 BLI measurement). Statistical significance was assessed using two-way ANOVA followed by Turkey’s multiple comparison test. * P < .05, ** P < .01 compared to ENPP1-KO JIMT-1-BR BrM-bearing mice. (D) Ex vivo imaging of GFP+ BC cells in the brain. The color scale shows radiant efficiency. (E) Representative images of histopathological H&E of whole brain sections showing the number and size of BrMs. Scale bars: 1 mm, in inserts: 250 µm. (F) Plasma levels of ENPP1 in healthy mice and mice bearing BrM from JIMT-1, WT JIMT-1-BR, LOXP-KO JIMT-1-BR, and ENPP1-KO JIMT-1-BR cells. Statistical significance was assessed using one-way ANOVA followed by Turkey’s multiple comparison test. **** P < .0001 compared to WT JIMT-1 BrM-bearing mice. Survival analysis by Kaplan–Meier showed a significantly shortened (G) overall survival ( P = .048) and (H) metastasis-free survival ( P = 0.0235) for mice bearing BrM from ENPP1-KO compared to LOXP-KO. Statistical significance was assessed using log-rank test. (I) Two-sided Pearson correlation was assessed between ENPP1 plasma levels and overall survival of mice. (J) Representative BLI images showing the progression of BrM formation over time in mice treated with an ENPP1 inhibitor ( n = 5) or vehicle ( n = 3). The color scale shows radiance (photons/sec/cm 2 /sr). (K) Representative images of histopathological H&E of whole brain sections showing brain metastatic foci. Scale bars: 1 mm, in inserts: 250 µm.

Article Snippet: Additionally, ENPP1 Inhibitor 4e (ENPP1i; Cayman Chemical; CAY-37687) was added at 10 μM during incubation with brain-tropic cell SCR for 24 hours.

Techniques: Knock-Out, Injection, Comparison, Ex Vivo, Imaging, Clinical Proteomics

Journal: Oncology Letters

Article Title: Role of ENPP1 in cancer pathogenesis: Mechanisms and clinical implications (Review)

doi: 10.3892/ol.2024.14722

Figure Lengend Snippet: Molecular mechanisms of ENPP1 in different human cancers. ABCG2, ATP binding cassette subfamily G member 2; AMPK, adenosine 5′-monophosphate-activated protein kinase; BAX, Bcl-2-associated X protein; Bcl-2, B-cell lymphoma 2; EMT, epithelial-mesenchymal transition; ENPP1, ectonucleotide pyrophosphatase/phosphodiesterase 1; E2F1, E2F transcription factor 1; GSC, glioma stem cell; Hp, haptoglobin; miR-27b, microRNA 27b; MMP9, matrix metalloproteinase 9; NANOG, Nanog Homeobox; NET, neutrophil extracellular traps; PCNA, proliferating cell nuclear antigen; TGF-β, transforming growth factor-β; ULK1, unc-51 like autophagy activating kinase 1.

Article Snippet: Of these, there is only one ongoing clinical trial of an oral, potent, selective small molecule inhibitor of ENPP1 called RBS2418 (Riboscience), which has the potential to activate an antitumor innate immune response leading to an antitumor response in adult patients with advanced or metastatic tumors, and the clinical results have not demonstrated toxicity with increasing doses ( ).

Techniques: Binding Assay

Journal: Oncology Letters

Article Title: Role of ENPP1 in cancer pathogenesis: Mechanisms and clinical implications (Review)

doi: 10.3892/ol.2024.14722

Figure Lengend Snippet: Major signaling pathways associated with ENPP1. (A) ENPP1 and cGAMP-STING pathway. (B) ENPP1-Hp signaling pathway. (C) ENPP1-E2F1 signaling pathway. (D) ENPP1-AMPK-ULK1-cell autophagy signaling pathway. AMP, adenosine monophosphate; AMPK, adenosine 5′-monophosphate-activated protein kinase; ATP, adenosine triphosphate; BAX, Bcl-2-associated X protein; Bcl-2, B-cell lymphoma 2; CD73, 5′-nucleotidase ecto; cGAMP, cyclic GMP-AMP; cGAS, cyclic-GMP-AMP synthase; CTC, circulating tumor cell; ENPP1, ectonucleotide pyrophosphatase/phosphodiesterase 1; E2F1, E2F transcription factor 1; GTP, guanosine triphosphate; Hp, haptoglobin; NET, neutrophil extracellular traps; PMN-MDSC, polymorphonuclear myeloid derived suppressor cells; STING, stimulator of interferon genes; ULK1, unc-51 like autophagy activating kinase 1. This figure was created using Figdraw 2.0 ( www.figdraw.com ).

Article Snippet: Of these, there is only one ongoing clinical trial of an oral, potent, selective small molecule inhibitor of ENPP1 called RBS2418 (Riboscience), which has the potential to activate an antitumor innate immune response leading to an antitumor response in adult patients with advanced or metastatic tumors, and the clinical results have not demonstrated toxicity with increasing doses ( ).

Techniques: Protein-Protein interactions, Derivative Assay

Journal: Frontiers in Immunology

Article Title: Small molecule innate immune modulators in cancer therapy

doi: 10.3389/fimmu.2024.1395655

Figure Lengend Snippet: List of innate immune modulators in cancer immunotherapy.

Article Snippet: In 2022, the first Phase I clinical trial was initiated for an orally available small molecule ENPP1 inhibitor, RBS2418 from Riboscience in combination with pembrolizumab or as a monotherapy for advanced unresectable, recurrent or metastatic tumors ( , ).

Techniques: