| Field | Specification |
|---|---|
| Target | |
| CAS no. | |
| Applications | |
| Molecular weight | |
| Molecular formula | C22H20F4N2O3 |
| SMILES | |
| Storage | |
| Shipping | |
| Catalog no. (Mfr.) | |
| Main SKU |
Compound Overview
EVT-401 is an orally active, highly selective antagonist of the human P2X7 receptor. Against human P2X7R it shows an IC50 reading of 10 nM alongside a Ki value of 7.6 nM, while against mouse P2X7R the IC50 is 220 nM. In human rheumatoid arthritis synovial fibroblasts (RA SF), it promotes apoptosis, induces cell cycle arrest, lowers production of proinflammatory and joint-destructive mediators, and reduces aggressive cell phenotypes. Favorable oral bioavailability and a good safety profile make it well suited to rheumatoid arthritis research[1]. It has the molecular formula C22H20F4N2O3 and a molecular weight of 436.40 g/mol.
Physical & Chemical Properties
| CAS Number | 951015-69-3 |
|---|---|
| Molecular Formula | C22H20F4N2O3 |
| Molecular Weight | 436.40 g/mol |
| SMILES | FC(C=C1CC(NC2=C3C(C(N(C=C3)[C@H](C)CO)=O)=CC=C2C)=O)=C(C=C1)C(F)(F)F |
| Target | hP2X7R, rP2X7R |
| Signaling Pathway | Membrane Transporter/Ion Channel; Apoptosis |
| Storage | Please store the product under the recommended conditions in the Certificate of Analysis. |
| Shipping | Room temperature in continental US; may vary elsewhere. |
Biological Activity
IC50 & Target[1]
|
hP2X7R 10 nM (IC50) |
hP2X7R 7.6 nM (Ki) |
rP2X7R 220 nM (IC50) |
Literature Cited
Sources cited in this description and in the In Vitro & In Vivo Data tab. Peer-reviewed publications that used this product are listed under References.
Safety
For Research Use Only. Not for use in diagnostic or therapeutic procedures, and not for human or veterinary use. Handle in accordance with your institution's chemical hygiene plan.
In Vitro
EVT-401 shows a Ki of 7.6 nM for hP2X7R in radioligand binding assays, and Schild analysis gives a KB of 12.1 nM[1]. In calcium flux assays using 1321N1 cells, EVT-401 blocks hP2X7R-mediated calcium influx with an IC50 of 10 nM, compared with an IC50 of 220 nM for rat P2X7R, and it does not significantly inhibit P2X1/2/3/4 family members[1]. At 10-200 μM for 24-96 h, EVT-401 shows low cytotoxicity in RA SF[1]. EVT-401 (50-200 μM; 24 or 48 h) increases apoptosis in RA SF, as determined by Annexin V/7-AAD flow cytometry[1]. In RA SF, EVT-401 (100 μM; 24 h) causes G0/G1 cell cycle arrest and lowers the levels of the G0/G1-related proteins Cdk2, Rb and p-Rb[1]. In a TNF-α-induced RA SF inflammatory model, EVT-401 (100 μM; 24 h) significantly decreases IL-6 secretion and downregulates MMP-3 and DKK-1 expression[1]. EVT-401 (10 or 100 μM; 24 h) suppresses RA SF migration and invasion, as shown in Transwell and wound healing assays[1].
Cell Viability Assay[1]
| Cell Line | RA SF |
|---|---|
| Concentration | 10, 50, 100 and 200 μM |
| Incubation Time | 24, 48, 72 and 96 h |
| Result | Showed low cytotoxicity in RA SF. |
Cell Proliferation Assay[1]
| Cell Line | RA SF |
|---|---|
| Concentration | 10, 50, 100 and 200 μM |
| Incubation Time | 24, 48, 72 and 96 h |
| Result | At 100 μM partially inhibited RA SF proliferation after 72 h, while concentrations below 100 μM showed no obvious antiproliferative effects within 24, 48 or 72 h. |
Apoptosis Analysis[1]
| Cell Line | RA SF |
|---|---|
| Concentration | 50, 100 and 200 μM |
| Incubation Time | 24 or 48 h |
| Result | Promoted apoptosis in RA SF, as detected by Annexin V/7-AAD flow cytometry. The pro-apoptotic effect was more obvious. |
Cell Cycle Analysis[1]
| Cell Line | RA SF |
|---|---|
| Concentration | 50, 100 and 200 μM |
| Incubation Time | 24 h |
| Result | Induced G0/G1 cell cycle arrest in RA SF. |
Cell Migration Assay [1]
| Cell Line | TNF-α-stimulated RA SF |
|---|---|
| Concentration | 10 and 100 μM |
| Incubation Time | 24 h |
| Result | Suppressed TNF-α-induced transwell migration of RA SF. |
Cell Invasion Assay[1]
| Cell Line | TNF-α-stimulated RA SF |
|---|---|
| Concentration | 10 and 100 μM |
| Incubation Time | 24 h |
| Result | Inhibited the invasive potential of RA SF through Matrigel-coated transwell membranes. |
Western Blot Analysis[1]
| Cell Line | RA SF |
|---|---|
| Concentration | 10 and 100 μM |
| Incubation Time | 24 h |
| Result | Reduced the levels of G0/G1 phase-related proteins, including Cdk2, Rb and p-Rb, in RA SF. |
In Vivo
In female Lewis rat collagen-induced arthritis models, EVT-401 given at 0.5, 5 and 50 mg/kg (p.o.; once daily; for 28 days) produces detectable differences in plasma concentrations[1]. In cynomolgus monkey collagen-induced arthritis models, EVT-401 (100 mg/kg; p.o.; once daily; for 8 weeks) significantly lowers clinical arthritis scores, trends toward lower serum CRP levels, and causes no obvious pathological damage in the heart, liver, spleen, lung or kidney by H&E staining[1]. In RA SF-cartilage co-transplantation NOD-SCID mouse models, EVT-401 given s.c. at 100 μM twice weekly for 21 days significantly inhibits RA SF invasion into cartilage[1]. In cynomolgus monkeys, EVT-401 has dose-dependent oral bioavailability of 42.2%, 30.9% and 26.6% at 10, 30 and 100 mg/kg, respectively[1].
| Animal Model | Female Lewis rats with collagen-induced arthritis[1] |
|---|---|
| Dosage | 0.5, 5, and 50 mg/kg |
| Administration | Oral gavage (p.o.); once daily; for 28 days |
| Result | Showed detectable differences in plasma concentrations. Did not exhibit significant therapeutic effects in this arthritis model. |
| Animal Model | Cynomolgus monkeys with collagen-induced arthritis[1] |
|---|---|
| Dosage | 100 mg/kg |
| Administration | Oral gavage (p.o.); once daily; for 8 weeks |
| Result | Significantly reduced clinical arthritis scores. Showed a decreasing trend in serum CRP levels. Did not cause obvious pathological damage in heart, liver, spleen, lung, or kidney by H&E staining. |
| Animal Model | NOD-SCID mice with RA SF-cartilage co-transplantation[1] |
|---|---|
| Dosage | 100 μM |
| Administration | Subcutaneous injection (s.c.); twice weekly; for 21 days |
| Result | Significantly inhibited RA SF invasion into cartilage. |
Data provided by the manufacturer. Numbered citations refer to the Literature Cited list in the product description.
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