N-[(1S)-1-(氨基羰基)-4 -[(2 - 氯-1-亚氨基乙基氨基]丁基]-苯甲酰胺 CAS#: 913723-61-2

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

中文名称	N-[(1S)-1-(氨基羰基)-4 -[(2 - 氯-1-亚氨基乙基氨基]丁基]-苯甲酰胺
中文同义词	N-[(1S)-1-(氨基羰基)-4 -[(2 - 氯-1-亚氨基乙基氨基]丁基]-苯甲酰胺;N-ALPHA-苯甲酰基-N5-(2-氯-1-亚氨基乙基)-1-鸟氨酰胺;化合物 T10831;(S)-N-(1-氨基-5-(2-氯乙脒)-1-氧代戊烷-2-基)苯甲酰胺;化合物 CL-AMIDINE
英文名称	Cl-Amidine
英文同义词	Cl-Amidine;N-[(1S)-1-(Aminocarbonyl)-4-[(2-chloro-1-iminoethyl)amino]butyl]-benzamideN-;N-[(1S)-1-(Aminocarbonyl)-4-[(2-chloro-1-iminoethyl)amino]butyl]benzamide;N-alpha-Benzoyl-N5-(2-chloro-1-iminoethyl)-1-ornithine amide;Benzamide, N-[(1S)-1-(aminocarbonyl)-4-[(2-chloro-1-iminoethyl)amino]butyl]-;Cl amidine,Clamidine;N-BCl-I-OA cpd;(S)-N-(1-Amino-5-(2-chloroacetimidamido)-1-oxopentan-2-yl)benzamide
CAS号	913723-61-2
分子式	C14H19ClN4O2
分子量	310.78
EINECS号
相关类别
Mol文件	913723-61-2.mol
结构式

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

储存条件	Store at -20°C
溶解度	溶于二甲基亚砜

N-[(1S)-1-(氨基羰基)-4 -[(2 - 氯-1-亚氨基乙基氨基]丁基]-苯甲酰胺用途与合成方法

生物活性

Cl-amidine 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 可诱导癌细胞的凋亡。Cl-amidine TFA 可诱导 miR-16，引起细胞周期阻滞。Cl-Amidine 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 irreversibly inactivates PADs by covalently modifying an active site cysteine that is important for its catalytic activity.

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.

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