Cl-amidine

上海金畔生物科技有限公司为生命科学和医药研发人员提供生物活性分子抑制剂、激动剂、特异性抑制剂、化合物库、重组蛋白,专注于信号通路和疾病研究领域。

Cl-amidine 

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 (miRNA-16, microRNA-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。

Cl-amidine

Cl-amidine Chemical Structure

CAS No. : 913723-61-2

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Cl-amidine 的其他形式现货产品:

Cl-amidine hydrochloride D-Cl-amidine hydrochloride

生物活性

Cl-amidine is an orally active peptidylarginine deminase (PAD) inhibitor, with IC50 values of 0.8 μM, 6.2 μM and 5.9 μM for PAD1, PAD3, and PAD4, respectively. Cl-amidine induces apoptosis in cancer cells. Cl-amidine induces microRNA (miR)-16 (miRNA-16, microRNA-16) expression and causes cell cycle arrest. Cl-Amidine 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-1•min-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].

Shanghai Jinpan Biotech Co Ltd has not independently confirmed the accuracy of these methods. They are for reference only.

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.

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].

Shanghai Jinpan Biotech Co Ltd has not independently confirmed the accuracy of these methods. They are for reference only.

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.

分子量

310.78

Formula

C14H19ClN4O2

CAS 号

913723-61-2

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.

参考文献
  • [1]. Yuan Luo, et al. Inhibitors and Inactivators of Protein Arginine Deiminase 4: Functional and Structural Characterization. Biochemistry. 2006 Oct 3; 45(39): 11727–11736.

    [2]. Chumanevich AA, et al. Suppression of colitis in mice by Cl-amidine: a novel peptidylarginine deiminase inhibitor. Am J Physiol Gastrointest Liver Physiol. 2011 Jun;300(6):G929-38.

    [3]. Witalison EE, et al. Molecular targeting of protein arginine deiminases to suppress colitis and prevent colon cancer. Oncotarget. 2015 Nov 3;6(34):36053-62.

    [4]. Biron BM, et al., Cl-Amidine Prevents Histone 3 Citrullination and Neutrophil Extracellular Trap Formation, and Improves Survival in a Murine Sepsis Model. J Innate Immun. 2017;9(1):22-32.

    [5]. Bryan Knuckley, et al. Substrate Specificity and Kinetic Studies of PADs 1, 3, and 4 Identify Potent and Selective Inhibitors of Protein Arginine Deiminase 3. Biochemistry. 2010 Jun 15;49(23):4852-63.

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