Enpp-1-IN-27
Enpp-1-IN-27 is a selective ENPP1 inhibitor with an IC50 of 14.68 nM, exhibiting approximately 410-fold selectivity against ENPP2 and 10-fold selectivity against ENPP3. Enpp-1-IN-27 stabilizes cGAMP levels and activates the STING pathway, promoting cytokine release and enhancing innate immune responses. Enpp-1-IN-27 induces ISRE activation and amplified cGAMP-mediated immune responses and shows the desired antitumor efficacy in the 4T1 and CT26 syngeneic mouse models. Enpp-1-IN-27 can used for the studies of breast cancer and colon cancer.
For research use only. We do not sell to patients.
- CAS No.: 3105103-33-8
- Formula: C13H19ClN6O3S
- Molecular Weight:374.85
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Storage:
Please store the product under the recommended conditions in the Certificate of Analysis.
To place orders, for customer services and technical support, please contact: MedChemExpress USA
Tel: 609-228-6898 E-mail: [email protected] [email protected]
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Biological Activity
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Chemical Information
- Protocols
- Purity & Documentation
- References
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Help & FAQs
Biological Activity
Description
In Vitro
Enpp-1-IN-27 (Compound 31) (0-50 μM, 25 h) enhances cGAMP-mediated STING activity more effectively than cGAMP alone in both THP-1 cells (EC50 = 16.5 μM) and HCT116 cells[1].
Enpp-1-IN-27 (25-50 μM, 4-25 h) stimulates type I interferon responses by activation of STING signaling pathway in THP-1 and HCT116 cells[1].
Enpp-1-IN-27 (10 μM) demonstrates negligible inhibition of five major CYP enzyme isoforms (CYP1A2, CYP2C9, CYP2C19, CYP2D6, and CYP3A4) and exhibits excellent metabolic stability, with microsomal stability exceeding 95% in human, mouse, and rat liver microsomes[1].
Enpp-1-IN-27 exhibits favorable kinetic solubility (191 μM) and demonstrates no significant inhibition of the human Ether-à-go-go-related gene (hERG) channel (IC50 > 100 μM)[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only. Further protocols information, click here.
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Cell Line:THP-1 cells and HFF cells
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Concentration:25 and 50 μM
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Incubation Time:Pretreat for 1 h and treated with 5 μM of cGAMP for 24 h
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Result:Significantly increased extracellular cytokine secretion compared to cGAMP treatment alone and demonstrated stronger innate immune activation than MV-658 in both THP-1 cells and HFF cells.
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Cell Line:THP-1 cells
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Concentration:25 and 50 μM
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Incubation Time:Pretreat for 1 h and treated with 5 μM of cGAMP for 6 h
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Result:Enhanced the phosphorylation of STING, TBK1, and IRF3, indicating robust activation of the STING signaling cascade.
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Cell Line:THP-1 cells
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Concentration:25 and 50 μM
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Incubation Time:Pretreat for 1 h and treated with 5 μM of cGAMP for 3 h
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Result:Increased the expression levels of representative interferon-stimulated genes (ISGs), including IFNB, ISG15 and IFIT3.
Parmacokinetics
| Species | Dose | Route | T1/2 | Tmax | Cmax | AUClast | AUCINF_obs | MRTlast | MRTINF_obs | Vss | CL | F |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Mice[1] | 1 mg/kg | i.v. | 0.50 h | 0.08 h | 424.56 ng/mL | 220.36 ng·h/mL | 225.36 ng·h/mL | 0.45 h | 0.52 h | 2287.18 mL/kg | 75.61 mL/min/kg | / |
| Mice[1] | 10 mg/kg | p.o. | 1.20 h | 1.17 h | 164.53 ng/mL | 527.27 ng·h/mL | 534.10 ng·h/mL | 2.11 h | 2.21 h | / | / | 23.93 % |
In Vivo
Enpp-1-IN-27 (50 mg/kg, i.p., single dose) has high safety and key biomarkers for liver toxicity. including aspartate transaminase (AST) and alanine trans-aminase (ALT), as well as kidney toxicity markers, such as blood Urea nitrogen (BUN) and serum creatinine both remained within the normal range[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:4T1 induced xenograft model established in female BALB/c mice (8 weeks old) [1]
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Dosage:50 mg/kg with or without anti-CTLA-4 antibodies (αCTLA-4)
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Administration:Intraperitoneal injection (i.p.), once daily for 15 days
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Result:Significantly inhibited tumor growth (47%) and the combination-treated group worked better (92%). No significant toxicity was observed during the administration period, as indicated by stable body weight and the absence ofhair loss.
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Animal Model:CT26 induced xenograft model established in female BALB/c mice (8 weeks old) [1]
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Dosage:50 mg/kg with or without anti-PD-L1
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Administration:Intraperitoneal injection (i.p.), once daily for 20 days
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Result:Showed significantly stronger anticancer effects in the combination therapy with PD-L1 blockade than ICIs monotherapy.
No significant toxicity was observed during the administration period, as indicated by stable body weight and the absence ofhair loss. Promoted T cell-mediated immune activation and facilitates the conversion of cold tumor into hot tumor.
Significantly increased CD80 expression (M1 marker) and decreased CD206 levels (M2 marker).
Enhanced infiltration ofDiD-labeled PBMCs into tumor spheroids, as visualized by fluorescence imaging.
Chemical Information
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CAS No. 3105103-33-8
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Molecular Weight 374.85
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Formula C13H19ClN6O3S
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SMILES
O=C1NC(N=CN=C2N3CCC(CNS(N)(=O)=O)(CC3)CCl)=C2C1
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
Please store the product under the recommended conditions in the Certificate of Analysis.
Protocols
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Cell Cytotoxicity Assay
Cytotoxicity assays are usually based on the assessment of cell membrane damage, which can also be indirectly detected by measuring cell viability. Detection methods include MTT assay, CKK-8 assay, LDH assay and ATP assay, etc.
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Patient-Derived Xenograft (PDX)
Patient-derived xenograft (PDX) models are generated by engrafting primary human tumor tissue directly into immunodeficient mice, allowing in vivo propagation of patient tumor biology without initial in vitro adaptation. These models are used to preserve key histopathological and molecular characteristics of the original tumor and enable assessment of tumor growth dynamics and therapeutic response in a living organism. The biological readout is tumor engraftment and subsequent growth in the murine host, which reflects the ability of human tumor cells to survive, vascularize, and expand in an immunocompromised microenvironment.
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Research Protocol for Inflammation-related Diseases
The NLRP3 inflammasome is a cytosolic innate immune signaling platform that integrates priming signals and danger-signal activation to promote caspase-1 activation, maturation of IL-1β and IL-18, and gasdermin D-mediated pyroptotic cell death. The core experimental logic is to determine whether inflammatory disease phenotypes are driven by increased NLRP3 expression, ASC-containing inflammasome assembly, caspase-1 cleavage, GSDMD cleavage, and extracellular release of IL-1β/IL-18 rather than by nonspecific cell injury alone. The pathway is strongly linked to inflammation-related disease phenotypes because monosodium urate crystals activate NALP3/NLRP3 inflammasome signaling in gout-like crystal inflammation, cholesterol crystals activate NLRP3 inflammasomes in atherogenesis models, and DSS-induced intestinal inflammation has been reported to involve NLRP3 inflammasome activity. However, experimental colitis studies also show context-dependent protective effects of NLRP3 inflammasome co
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Breast Cancer Modeling
Breast cancer is a heterogeneous cancer, and it has been distinguished into four subtypes: luminal A, luminal B, HER2-positive and basal-like. Molecular mutations, epigenetic alterations, hormone exposure and immune microenvironment are related to the progression of breast cancer.
Purity & Documentation
References
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
Enpp-1-IN-27 Related Classifications
HY-175478 Related Classifications
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