YS3074
YS3074 is a selective ENPP1 inhibitor with an IC50 of 4.23 nM. YS3074 inhibits ENPP1-mediated hydrolysis of extracellular cGAMP, thereby preserving cGAMP to activate the STING signaling pathway. YS3074 exhibits antitumor effects both as a single agent and in combination with anti-PD-1 antibodies, enhancing tumor growth inhibition and prolonging survival. YS3074 can be used for research on colorectal cancer.
For research use only. We do not sell to patients.
- Formula: C25H23F3N5O4P
- Molecular Weight:545.45
-
Storage:
Please store the product under the recommended conditions in the Certificate of Analysis.
Biological Activity
Description
Cellular Effect
|
Cell Line
|
Type | Value | Description | References |
|---|---|---|---|---|
| MDA-MB-231 | IC50 |
60.4 nM
|
Inhibition of cellular ENPP1 activity in human MDA-MB-231 cells using thymidine-5′-monophosphate p-nitrophenyl ester as substrate after 60 min incubation measured by absorbance at 405 nm.
Inhibition of cellular ENPP1 activity in human MDA-MB-231 cells using thymidine-5′-monophosphate p-nitrophenyl ester as substrate after 60 min incubation measured by absorbance at 405 nm.
|
42648057 |
| CHO-K1 | IC50 |
>30 μM
|
Inhibition of hERG current in CHO-K1 cells transfected with hERG measured by whole-cell patch-clamp with IC50 >30 μM.
Inhibition of hERG current in CHO-K1 cells transfected with hERG measured by whole-cell patch-clamp with IC50 >30 μM.
|
42648057 |
In Vitro
YS3074 (10 min) inhibits recombinant ENPP1 with an IC50 of 4.23 nM and is selective against ENPP2 (>10000 nM) and ENPP3 (4060 nM)[1].
YS3074 (pre-incubation for 10 min followed by enzymatic reaction for 60 min) inhibits cellular ENPP1 activity in MDA-MB-231 cells with an IC50 of 60.4 nM[1].
YS3074 (24 h) did not show significant cytotoxicity in THP-1, THP1-Blue ISG, and THP1-Dual KO-STING cells[1].
YS3074 (1-30 μM) weakly inhibits hERG currents in CHO-K1 cells, with an IC50 >30 μM[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only. Further protocols information, click here.
-
Cell Line:human THP-1-derived macrophages and murine RAW 264.7 macrophages
-
Concentration:YS3074 serial dilutions (maximum final concentration 10 μM); cGAMP 2 μM (THP-1) or 5 μM (RAW 264.7); PMA 100 nM
-
Incubation Time:12 h (initial incubation); 1 h (YS3074 preincubation); indicated time points (collection)
-
Result:Enhanced cGAMP-induced mRNA expression of IFNB1, CXCL10, and IL6 in a dose-dependent manner.
In time-course experiments, YS3074 produced stronger and longer-lasting STING target gene expression.
No obvious cytotoxicity was observed within the tested concentration range.
-
Cell Line:THP-1, THP1-Blue ISG, and THP1-Dual KO-STING cells
-
Concentration:YS3074 serial dilutions; PMA 100 nM
-
Incubation Time:12 h (PMA differentiation); 24 h (YS3074 incubation)
-
Result:Did not show obvious cytotoxicity within the tested concentration range.
In Vivo
YS3074 (40 mg/kg; i.p.; daily) combined with anti-PD-1 antibody produces up to 73% tumor growth inhibition and prolongs survival in the CT-26 subcutaneous BALB/c mouse model[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
-
Animal Model:BALB/c (female, 6-8 weeks old)[1]
-
Dosage:15 mg/kg; 40 mg/kg
-
Administration:i.p.; daily
-
Result:Monotherapy at 40 mg/kg achieved a tumor growth inhibition rate of 40% in the CT-26 subcutaneous tumor model.
-
Animal Model:BALB/c (female, 6-8 weeks old)[1]
-
Dosage:15 mg/kg; 40 mg/kg
-
Administration:i.p.; daily; anti-PD-1 antibody i.p. every other day
-
Result:In combination with anti-PD-1 antibody, YS3074 at 15 mg/kg achieved a tumor growth inhibition rate of 48%, and at 40 mg/kg achieved a tumor growth inhibition rate of 73%, in the CT-26 subcutaneous tumor model.
Mouse survival was prolonged.
Chemical Information
-
Molecular Weight 545.45
-
Formula C25H23F3N5O4P
-
SMILES
FC(C=CC=C1F)=C1C2=NC(C(NC3=CC(F)=CC=C3N4CCC(CP(O)(O)=O)CC4)=O)=CN5C2=NC=C5
-
Shipping
Room temperature in continental US; may vary elsewhere.
-
Storage
Please store the product under the recommended conditions in the Certificate of Analysis.
Protocols
-
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.
-
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.
-
Patient-Derived Orthotopic Xenograft (PDOX)
Patient-derived orthotopic xenograft (PDOX) modeling implants fresh patient tumor tissue or patient-derived tumor cells into the anatomically corresponding organ or tissue site of immunodeficient mice, usually by surgical orthotopic implantation, to preserve patient tumor histology, local microenvironmental context, invasion, metastatic behavior, and treatment-response features better than subcutaneous implantation. PDOX readouts include tumor engraftment, orthotopic tumor growth, local invasion, metastasis, recurrence after resection, histologic similarity to the donor tumor, biomarker retention, molecular concordance, survival, and response or resistance to therapy. PDOX models are used for preclinical drug testing and individualized therapy evaluation, but engraftment success varies by tumor type and specimen quality.
-
Subcutaneous Cell-Line-Derived Xenograft
Subcutaneous cell-line-derived xenograft (CDX) models are established by implanting cultured human cancer cell lines into immunodeficient mice, where the injected cells form localized tumors that can be monitored in vivo as a measure of tumorigenic potential, growth kinetics, and treatment response. These models are widely used in oncology research because they allow reproducible tumor formation and enable comparative assessment of tumor growth between different cell lines or genetic manipulations in a controlled in vivo microenvironment. Subcutaneous implantation of cancer cells in immunodeficient mice is a standard approach for evaluating tumor growth behavior and therapeutic response across multiple cancer types, including prostate, esophageal, pancreatic, and colon cancer models.
-
Orthotopic Cell-Line Xenograft
Orthotopic cell-line xenograft models involve implantation of human cancer cell lines into the anatomically corresponding organ of immunodeficient mice to reproduce tumor growth within a native microenvironment, enabling more clinically relevant tumor behavior compared with subcutaneous models. These models are widely used because orthotopic placement better recapitulates tumor progression, including invasion and metastatic spread, which are often underrepresented in heterotopic implantation systems. Compared with conventional xenografts, orthotopic implantation is described as more technically complex but provides improved simulation of tumor-microenvironment interactions and metastatic behavior, making it particularly valuable for translational oncology research. Surgical orthotopic implantation approaches have been emphasized as enabling faithful reproduction of clinical cancer features, including metastasis and disease progression patterns that align with the tumor’s organ of origi
Purity & Documentation
References
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)