1043444-18-3

1043444-18-3 structure

Name: Cl-amidine TFA
Chemical Name: N-{(2S)-1-Amino-5-[(2-chloroethanimidoyl)amino]-1-oxo-2-pentanyl}benzamide trifluoroacetate (1:1)
CAS Number: 1043444-18-3
Molecular Formula: C₁₆H₂₀ClF₃N₄O₄
Molecular Weight: 424.803
Catalog: Signaling Pathways Apoptosis Apoptosis
Create Date: 2018-04-08 00:57:27
Modify Date: 2024-01-02 09:24:28
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 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].

Name	N-{(2S)-1-Amino-5-[(2-chloroethanimidoyl)amino]-1-oxo-2-pentanyl}benzamide trifluoroacetate (1:1)
Synonyms	N-{(2S)-1-Amino-5-[(2-chloroethanimidoyl)amino]-1-oxo-2-pentanyl}benzamide trifluoroacetate (1:1) Acetic acid, 2,2,2-trifluoro-, compd. with N-[(1S)-1-(aminocarbonyl)-4-[(2-chloro-1-iminoethyl)amino]butyl]benzamide (1:1) Cl-amidine

Description	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 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].
Related Catalog	Signaling Pathways >> Apoptosis >> Apoptosis Research Areas >> Cancer Signaling Pathways >> Epigenetics >> MicroRNA Research Areas >> Inflammation/Immunology Signaling Pathways >> Epigenetics >> Protein Arginine Deiminase
Target	IC50: 0.8 μM (PAD1), 5.9 μM (PAD4), 6.2 μM (PAD3)[1][5].
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]. 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.
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.
References	[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.

Molecular Formula	C₁₆H₂₀ClF₃N₄O₄
Molecular Weight	424.803
Exact Mass	424.112518
Storage condition	-20℃

Hazard Codes	N

1043444-18-3	1373232-26-8
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1101220-90-9	84809-63-2