Cl-amidine TFA 

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]}.

IC50: 0.8 μM (PAD1), 5.9 μM (PAD4), 6.2 μM (PAD3)^[1][5].

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)^[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].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

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].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

424.80

C₁₆H₂₀ClF₃N₄O₄

1043444-18-3

O=C(N[C@H](C(N)=O)CCCNC(CCl)=N)C1=CC=CC=C1.O=C(O)C(F)(F)F

Room temperature in continental US; may vary elsewhere.

Please store the product under the recommended conditions in the Certificate of Analysis.

• [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.  [Content Brief]

  [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.  [Content Brief]

  [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.  [Content Brief]

  [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.  [Content Brief]

  [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.  [Content Brief]