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
-
Storage:
Please store the product under the recommended conditions in the Certificate of Analysis.
-
Biological Activity
-
Chemical Information
- Purity & Documentation
- References
-
Help & FAQs
Biological Activity
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.
-
Cell Line:THP-1 cells and HFF cells
-
Concentration:25 and 50 μM
-
Incubation Time:Pretreat for 1 h and treated with 5 μM of cGAMP for 24 h
-
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.
-
Cell Line:THP-1 cells
-
Concentration:25 and 50 μM
-
Incubation Time:Pretreat for 1 h and treated with 5 μM of cGAMP for 6 h
-
Result:Enhanced the phosphorylation of STING, TBK1, and IRF3, indicating robust activation of the STING signaling cascade.
-
Cell Line:THP-1 cells
-
Concentration:25 and 50 μM
-
Incubation Time:Pretreat for 1 h and treated with 5 μM of cGAMP for 3 h
-
Result:Increased the expression levels of representative interferon-stimulated genes (ISGs), including IFNB, ISG15 and IFIT3.
| 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 % |
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.
-
Animal Model:4T1 induced xenograft model established in female BALB/c mice (8 weeks old) [1]
-
Dosage:50 mg/kg with or without anti-CTLA-4 antibodies (αCTLA-4)
-
Administration:Intraperitoneal injection (i.p.), once daily for 15 days
-
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.
-
Animal Model:CT26 induced xenograft model established in female BALB/c mice (8 weeks old) [1]
-
Dosage:50 mg/kg with or without anti-PD-L1
-
Administration:Intraperitoneal injection (i.p.), once daily for 20 days
-
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
-
CAS No. 3105103-33-8
-
Molecular Weight 374.85
-
Formula C13H19ClN6O3S
-
SMILES
O=C1NC(N=CN=C2N3CCC(CNS(N)(=O)=O)(CC3)CCl)=C2C1
-
Shipping
Room temperature in continental US; may vary elsewhere.
-
Storage
Please store the product under the recommended conditions in the Certificate of Analysis.
Purity & Documentation
References
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
Powered by Bioz