N-[(1S)-1-(氨基羰基)-4 -[(2 - 氯-1-亚氨基乙基氨基]丁基]-苯甲酰胺盐酸盐

生物活性靶点体外研究体内研究 N-[(1S)-1-(氨基羰基)-4 -[(2 - 氯-1-亚氨基乙基氨基]丁基]-苯甲酰胺盐酸盐试剂级价格

CAS号:1373232-26-8
英文名:N-[(1S)-1-(Aminocarbonyl)-4-[(2-chloro-1-iminoethyl)amino]butyl]-benzamide hydrochloride
中文名:N-[(1S)-1-(氨基羰基)-4 -[(2 - 氯-1-亚氨基乙基氨基]丁基]-苯甲酰胺盐酸盐
CBNumber:CB52746936
分子式:C14H20Cl2N4O2
分子量:347.2402
MOL File:1373232-26-8.mol

N-[(1S)-1-(氨基羰基)-4 -[(2 - 氯-1-亚氨基乙基氨基]丁基]-苯甲酰胺盐酸盐化学性质

储存条件 :Store at -20°C
溶解度 :DMF: 14 mg/ml; DMSO: 50 mg/ml; Ethanol: 20 mg/ml; PBS (pH 7.2): 3 mg/ml
形态 :A crystalline solid
颜色 :White to light yellow

N-[(1S)-1-(氨基羰基)-4 -[(2 - 氯-1-亚氨基乙基氨基]丁基]-苯甲酰胺盐酸盐性质、用途与生产工艺

生物活性 Cl-amidine hydrochloride 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 hydrochloride 可诱导癌细胞的凋亡。Cl-amidine hydrochloride 可诱导 miR-16，引起细胞周期阻滞。Cl-Amidine hydrochloride 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。
靶点

IC50: 0.8 μM (PAD1), 5.9 μM (PAD4), 6.2 μM (PAD3).

体外研究

Cl-amidine is a bioavailable haloacetamidine-based compound that inhibits all the active PAD isozymes with near equal potency (k _inact /K _I =13,000 M _-1 •min-1 for PAD4).
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.
Cl-Amidine prevents histone 3 citrullination and neutrophil extracellular trap formation, and improves survival in a murine sepsis model.

Apoptosis Analysis.

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.

体内研究

Cl-amidine (75 mg/kg, ip once daily) suppresses and treats DSS-induced colitis in mice.
Cl-amidine (5, 25, 75 mg/kg, oral gavage, once daily) leads to significant reductions in the histology scores dose-dependently.

Animal Model:	C57BL/6 mice (8-12 wk old, DSS mouse model of colitis).
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).
Dosage:	5, 25, 75 mg/kg.
Administration:	Oral gavage once daily.
Result:	Led to significant reductions in the histology scores.