D-Cl-amidine hydrochloride is a potent and highly selective PAD1 inhibitor. D-Cl-amidine is well-torelated with no significant toxicity[1].
体外研究 (In Vitro)
D-Cl-amidine (200-400 μM) is effective in significantly decreasing cell viability in MDA-MB-231 cells[1]. D-Cl-amidine increase caspase 3 activity, indicating that inhibition of PAD1 leads to an increase in apoptosis[1].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
体内研究 (In Vivo)
D-Cl-amidine, administered by iv at a dose of 2.5 mg/kg, is still detected after 2 h in serum at a concentration of ~21 nM and at 4 h at ~10 nM. D-Cl-amidine is still observed in the blood serum at a concentration of ∼10 nM at 4 h when administered by ip at a dose of 10 mg/kg[1].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
分子量
347.24
Formula
C14H20Cl2N4O2
运输条件
Room temperature in continental US; may vary elsewhere.
储存方式
-20°C, protect from light, stored under nitrogen
*In solvent : -80°C, 6 months; -20°C, 1 month (protect from light, stored under nitrogen)
溶解性数据
In Vitro:
DMSO : 80 mg/mL (230.39 mM; ultrasonic and warming and heat to 60°C)
H2O : 16.67 mg/mL (48.01 mM; ultrasonic and warming and heat to 60°C)
配制储备液
浓度溶剂体积质量
1 mg
5 mg
10 mg
1 mM
2.8799 mL
14.3993 mL
28.7985 mL
5 mM
0.5760 mL
2.8799 mL
5.7597 mL
10 mM
0.2880 mL
1.4399 mL
2.8799 mL
*
请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液;一旦配成溶液,请分装保存,避免反复冻融造成的产品失效。 储备液的保存方式和期限:-80°C, 6 months; -20°C, 1 month (protect from light, stored under nitrogen)。-80°C 储存时,请在 6 个月内使用,-20°C 储存时,请在 1 个月内使用。
In Vivo:
请根据您的实验动物和给药方式选择适当的溶解方案。以下溶解方案都请先按照 In Vitro 方式配制澄清的储备液,再依次添加助溶剂:
[1]. Bicker KL, et al. D-amino acid based protein arginine deiminase inhibitors: Synthesis, pharmacokinetics, and in cellulo efficacy. ACS Med Chem Lett. 2012 Oct 26;3(12):1081-1085.
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].
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.
Cl-amidine hydrochloride 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 hydrochloride induces apoptosis in cancer cells. Cl-amidine hydrochloride induces microRNA (miR)-16 (miRNA-16, microRNA-16) expression and causes cell cycle arrest. Cl-Amidine hydrochloride prevents histone 3 citrullination and neutrophil extracellular trap formation, and improves survival in a murine sepsis model[1][2][3][4][5].
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 prevents histone 3 citrullination and neutrophil extracellular trap formation, and improves survival in a murine sepsis model[4].
上海金畔生物科技有限公司 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].
上海金畔生物科技有限公司 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
347.24
Formula
C14H20Cl2N4O2
CAS 号
1373232-26-8
运输条件
Room temperature in continental US; may vary elsewhere.
Solubility: 5.5 mg/mL (15.84 mM); Clear solution; Need ultrasonic
*以上所有助溶剂都可在 上海金畔生物科技有限公司 网站选购。
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.
D-Cl-amidine is a potent and highly selective PAD1 inhibitor. D-Cl-amidine is well-torelated with no significant toxicity[1].
体外研究 (In Vitro)
D-Cl-amidine (200-400 μM) is effective in significantly decreasing cell viability in MDA-MB-231 cells[1]. D-Cl-amidine increase caspase 3 activity, indicating that inhibition of PAD1 leads to an increase in apoptosis[1].
Shanghai Jinpan Biotech Co Ltd has not independently confirmed the accuracy of these methods. They are for reference only.
体内研究 (In Vivo)
D-Cl-amidine, administered by iv at a dose of 2.5 mg/kg, is still detected after 2 h in serum at a concentration of ~21 nM and at 4 h at ~10 nM. D-Cl-amidine is still observed in the blood serum at a concentration of ∼10 nM at 4 h when administered by ip at a dose of 10 mg/kg[1].
Shanghai Jinpan Biotech Co Ltd has not independently confirmed the accuracy of these methods. They are for reference only.
分子量
310.78
Formula
C14H19ClN4O2
CAS 号
1404060-15-6
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]. Bicker KL, et al. D-amino acid based protein arginine deiminase inhibitors: Synthesis, pharmacokinetics, and in cellulo efficacy. ACS Med Chem Lett. 2012 Oct 26;3(12):1081-1085.
Cl-amidine TFA 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 TFA induces apoptosis in cancer cells. Cl-amidine TFA induces microRNA (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].
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
424.80
Formula
C16H20ClF3N4O4
CAS 号
1043444-18-3
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.