EVT-401
EVT-401 is an orally active, potent and highly selective human P2X7R antagonist, with an IC50 of 10 nM and a Ki of 7.6 nM for human P2X7R, and an IC50 of 220 nM for mouse P2X7R. EVT-401 promotes apoptosis and induces cell cycle arrest in human rheumatoid arthritis synovial fibroblasts (RA SF), reduces the production of proinflammatory and joint-destructive mediators, and mitigates aggressive phenotypes. EVT-401 exhibits favorable oral bioavailability and a good safety profile, making it suitable for research into rheumatoid arthritis.
商品は「研究用試薬」です。人や動物の医療用・臨床診断用・食品用の製品ではありません。
研究用途以外に使用した場合、当社は一切の責任を負いかねます。
- CAS 番号: 951015-69-3
- 分子式: C22H20F4N2O3
- 分子量:436.40
-
保管条件:
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]
-
生物活性
-
化学情報
- 純度とドキュメンテーション
- 参考文献
-
Help & FAQs
P2X Receptor アイソフォーム固有の製品をすべて表示
More
生物活性
|
hP2X7R 10 nM (IC50) |
hP2X7R 7.6 nM (Ki) |
rP2X7R 220 nM (IC50) |
EVT-401 binds to hP2X7R with a Ki of 7.6 nM in radioligand binding assays, and Schild analysis yields a KB of 12.1 nM[1].
EVT-401 inhibits hP2X7R-mediated calcium influx with an IC50 of 10 nM in calcium flux assays using 1321N1 cells, whereas its IC50 for rat P2X7R is 220 nM, and it shows no significant inhibition of P2X1/2/3/4 family members[1].
EVT-401 (10-200 μM; 24-96 h) exhibits low cytotoxicity in RA SF [1].
EVT-401 (50-200 μM; 24 or 48 h) promotes apoptosis in RA SF as determined by Annexin V/7-AAD flow cytometry[1].
EVT-401 (100 μM; 24 h) induces G0/G1 cell cycle arrest in RA SF and reduces the levels of G0/G1-related proteins including Cdk2, Rb and p-Rb[1].
EVT-401 (100 μM; 24 h) significantly reduces IL-6 secretion and downregulates MMP-3 and DKK-1 expression in a TNF-α-induced RA SF inflammatory model[1].
EVT-401 (10 or 100 μM; 24 h) inhibits the migration and invasion of RA SF in Transwell and wound healing assays[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
-
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 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.
-
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 Line:RA SF
-
Concentration:50, 100 and 200 μM
-
Incubation Time:24 h
-
Result:Induced G0/G1 cell cycle arrest in RA SF.
-
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 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.
-
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.
| Species | Dose | Route | AUC0-t | MRT0-t | T1/2 | Tmax | CLz/F | Vz/F | Cmax |
|---|---|---|---|---|---|---|---|---|---|
| Cynomolgus Monkey[1] | 10 mg/kg | p.o. | 5407.69 μg/L·h | 11.65 h | 10.56 h | 3 h | 1.76 L/h/kg | 26.39 L/kg | 403.51 μg/L |
| Cynomolgus Monkey[1] | 100 mg/kg | p.o. | 34246.4 μg/L·h | 12.61 h | 9.87 h | 5.67 h | 3.15 L/h/kg | 45.94 L/kg | 2457.04 μg/L |
| Cynomolgus Monkey[1] | 30 mg/kg | p.o. | 11940.18 μg/L·h | 13.49 h | 12.86 h | 2.29 h | 2.46 L/h/kg | 42.66 L/kg | 891.24 μg/L |
EVT-401 (100 mg/kg; p.o.; once daily; for 8 weeks) significantly reduces clinical arthritis scores, shows a decreasing trend in serum CRP levels, and does not cause obvious pathological damage in the heart, liver, spleen, lung or kidney as assessed by H&E staining in cynomolgus monkey collagen-induced arthritis models[1].
EVT-401 (100 μM; s.c.; twice weekly; for 21 days) significantly inhibits RA SF invasion into cartilage in RA SF-cartilage co-transplantation NOD-SCID mouse models[1].
EVT-401 shows dose-dependent oral bioavailability of 42.2%, 30.9% and 26.6% at doses of 10, 30 and 100 mg/kg, respectively, in cynomolgus monkeys[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
-
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.
化学情報
-
CAS 番号 951015-69-3
-
分子量 436.40
-
分子式 C22H20F4N2O3
-
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
-
輸送条件
Room temperature in continental US; may vary elsewhere.
-
保管条件
Please store the product under the recommended conditions in the Certificate of Analysis.
純度とドキュメンテーション
参考文献
Calculators
濃度 (開始) × 体積 (開始) = 濃度 (終了) × 体積 (終了)
EVT-401 関連分類
HY-178230 関連分類
Powered by Bioz