Cl-Amidine (trifluoroacetate salt) |
| Catalog No.: GC11032 |
Cl-Amidine (trifluoroacetate salt) 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.
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.:1043444-18-3
Sample solution is provided at 25 µL, 10mM.
Quality Control & SDS
- View current batch:
-
Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
|
Cell experiment: |
TK6 cells are a lymphoblastoid cell line derived from the spleen >30 years ago. HT29 cells are a colon cancer cell line, with mutant p53. TK6 lymphoblastoid cells and HT29 colon cancer cells are cultured with Cl-amidine in a dose-dependent manner (0, 5, 10, 15, 20, 25, 50 μg/mL) over 24 h. Apoptosis is assessed by annexin V/propidium iodide staining followed by flow cytometry[2]. |
|
Animal experiment: |
Mice[2]C57BL/6 mice (8-12 wk old) are fed a standard AIN 93M diet. For this DSS mouse model of colitis, mice receive water ad libitum or 2% DSS beginning at day 0 [for oral gavage/treatment experiment or day 7 [for intraperitoneal/prevention experiment. Initial experiments used injections of Cl-amidine (75 mg/kg-1/day-1 ip), beginning concomitantly with the initiation of 2% DSS in the drinking water. This dose is chosen based on results in a RA model that used 100 mg/kg-1/day-1 without overt side effects and without immunosuppressive outcomes. In DSS model, 50 mice in 4 groups are examined, and inflammation scores are recorded[2]. |
|
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. |
|
IC50: 5.9 μM
Cl-Amidine is a PAD4 deimination activity inhibitor.
Protein arginine deiminase 4 (PAD4) can catalyze the post-translational modification of arginine residues on histones to form citrulline, which can change gene expression. Thus, dysregulated PAD4 activity has been implicated in cancer and rheumatoid arthritis.
In vitro: Previous study found that Cl-amidine antagonized the PAD4-mediated enhancement of the the p300GBD-GRIP1 interaction dose-dependently, and it was noteworthy that Cl-amidine treatment had only a minimal reduction in the efficiency of the interaction in Cys645S-transfected cells, thereby suggesting that the inhibitory effect of Cl-amidine was not a nonspecific one but was targeted at the active PAD4 enzyme. These results demonstrated that Cl-amidine was significantly more potent than F-amidine, consistent with its improved in vitro potency [1].
In vivo: Animal study showed that Cl-amidine could improve survival in a mouse model of cecal ligation and puncture (CLP)-induced septic shock. Cl-amidine was proven to play protective roles by restoring innate immune cells in BM, decreasing BM and thymus atrophy, increasing blood monocytes and blood/liver bacteria clearance, and attenuating pro-inflammatory cytokine production in a murine lethal sepsis model [2].
Clinical trial: So far, no clinical study has been conducted.
References:
[1] Luo, Y. ,Arita, K.,Bhatia, M., et al. Inhibitors and inactivators of protein arginine deiminase 4: Functional and structural characterization. Biochemistry 45(39), 11727-11736 (2006).
[2] Zhao T, Pan B, Alam HB, Liu B, Bronson RT, Deng Q, Wu E, Li Y. Protective effect of Cl-amidine against CLP-induced lethal septic shock in mice. Sci Rep. 2016 Nov 7;6:36696.
| Cas No. | 1043444-18-3 | SDF | |
| Chemical Name | N-[(1S)-1-(aminocarbonyl)-4-[(2-chloro-1-iminoethyl)amino]butyl]-benzamide 2,2,2-trifluoroacetate | ||
| Canonical SMILES | O=C(N[C@@H](CCCNC(CCl)=N)C(N)=O)C1=CC=CC=C1.FC(F)(C(O)=O)F | ||
| Formula | C14H19ClN4O2 • CF3CO2H | M.Wt | 424.8 |
| Solubility | DMF: 14 mg/ml, DMSO: 100 mg/ml, water: 3 mg/ml | Storage | Store at -20°C |
| General tips | For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months. | ||
| Shipping Condition | Evaluation sample solution : ship with blue ice All other available size: ship with RT , or blue ice upon request |
||
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
g
μL
Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)
Calculation results:
Working concentration: mg/ml;
Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )
Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL saline, mix and clarify.
Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.
Average Rating: 5 (Based on Reviews and 33 reference(s) in Google Scholar.)
GLPBIO products are for RESEARCH USE ONLY. Please make sure your review or question is research based.
Required fields are marked with *