Cl-amidine TFA 是口服有效的PAD抑制剂，其对 PAD1、PAD3 和 PAD4 的IC50值分别为0.8 μM、 6.2 μM 和5.9 μM。Cl-amidine TFA 可诱导癌细胞的凋亡。Cl-amidine TFA 可诱导 miR-16 (miRNA-16, microRNA-16)，引起细胞周期阻滞。Cl-Amidine TFA 可阻断组蛋白 3 瓜氨酸化和中性粒细胞胞外陷阱的形成，并提高败血症小鼠的存活率。
| 生物活性 | Cl-amidine TFA is an orally activepeptidylarginine deminase (PAD)inhibitor, withIC50values of 0.8 μM, 6.2 μM and 5.9 μM for PAD1, PAD3, and PAD4, respectively. Cl-amidine TFA inducesapoptosisincancercells. Cl-amidine TFA inducesmicroRNA(miR)-16 (miRNA-16, microRNA-16) expression and causes cell cycle arrest. Cl-Amidine TFA prevents histone 3 citrullination and neutrophil extracellular trap formation, and improves survival in a murine sepsis model[1][2][3][4][5]. |
| IC50& Target | IC50: 0.8 μM (PAD1), 5.9 μM (PAD4), 6.2 μM (PAD3)[1][5]. |
体外研究
(In Vitro) | Cl-amidine is a bioavailable haloacetamidine-based compound that inhibits all the active PAD isozymes with near equal potency (kinact/KI=13,000 M-1omin-1 for PAD4)[1].
Cl-amidine (0, 5, 10, 15, 20, 25, 50 μg/mL, 24 hours) induces apoptosis in TK6 lymphoblastoid cells and HT29 colon cancer cells in a dose-dependent manner. Interestingly, the colon cancer cell line (HT29) is relatively resistant to apoptosis caused by Cl-amidine[2].
Cl-amidine irreversibly inactivates PADs by covalently modifying an active site cysteine that is important for its catalytic activity[4].
Apoptosis Analysis[2]. | Cell Line: | TK6 lymphoblastoid cells and HT29 colon cancer cells. | | Concentration: | 0, 5, 10, 15, 20, 25, 50 μg/mL. | | Incubation Time: | 24 h. | | Result: | Induced apoptosis dose-dependently. |
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体内研究
(In Vivo) | Cl-amidine (75 mg/kg, ip once daily) suppresses and treats DSS-induced colitis in mice[2].
Cl-amidine (5, 25, 75 mg/kg, oral gavage, once daily) leads to significant reductions in the histology scores dose-dependently[2].
| Animal Model: | C57BL/6 mice (8-12 wk old, DSS mouse model of colitis)[2]. | | Dosage: | 75 mg/kg. | | Administration: | IP once daily. | | Result: | Suppressed PAD activity, protein citrullination, and PAD levels in the colon in vivo. |
| Animal Model: | C57BL/6 mice (8-12 wk old, DSS mouse model of colitis)[2]. | | Dosage: | 5, 25, 75 mg/kg. | | Administration: | Oral gavage once daily. | | Result: | Led to significant reductions in the histology scores. |
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| 运输条件 | Room temperature in continental US; may vary elsewhere. |
| 储存方式 | Please store the product under the recommended conditions in the Certificate of Analysis. |
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