Cl-amidine

Cas No.:	1043444-18-3
Chemical Name:	Cl-amidine (TFA)
Synonyms:	Cl-Amidine (trifluoroacetate salt);Cl-amidine (TFA);(2S)-5-(2-Chloroethanimidamido)-2-(phenylformamido)pentanamide trifluoroacetic acid salt;s8141;ZB1554;Cl-amidine 2,2,2-trifluoroacetic acid;(S)-N-(1-amino-5-(2-chloroacetimidamido)-1-oxopentan-2-yl)benzamide 2,2,2-trifluoroacetate
SMILES:	ClC([H])([H])/C(/N([H])[H])=N\C([H])([H])C([H])([H])C([H])([H])[C@@]([H])(C(N([H])[H])=O)N([H])C(C1C([H])=C([H])C([H])=C([H])C=1[H])=O.FC(C(=O)O[H])(F)F
Formula:	C16N4O4F3ClH20
M.Wt:	424.8026
Purity:	>98%
Sotrage:	2 years -20°C Powder, 2 weeks 4°C in DMSO, 6 months -80°C in DMSO

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].
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.
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.
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.