[CAS NO. 1373232-26-8] Cl-amidine hydrochloride
PRODUCTS SPECIFICATIONS [1373232-26-8]
DESCRIPTION [1373232-26-8]
Overview
| MDL | MFCD22201084 |
|---|---|
| Molecular Weight | 347.24 |
| Molecular Formula | C14H20Cl2N4O2 |
| SMILES | O=C(N[C@H](C(N)=O)CCCNC(CCl)=N)C1=CC=CC=C1.[H]Cl |
8 Publications Citing Use of MCE
- [1]Cell Rep. 2021 Sep 21;36(12):109750.
- [2]Neoplasia. 2022 Nov;33:100835.
- [3]Transl Res. 2022 Nov 23;S1931-5244(22)00252-3.
- [4]Fish Shellfish Immunol. 2022 Aug 3;S1050-4648(22)00414-4.
- [5]Chem Res Toxicol. 2022 Feb 15.
- [6]Microb Pathogenesis. 2020 Dec;149:104530.
- [7]Vet Parasitol. 2022 Nov 19;312:109841.
- [8]Research Square Print. January 4th, 2023.
Summary
Cl-amidine hydrochloride is an orally active peptidylarginine deminase (PAD) inhibitor, with IC 50 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] .
In Vitro
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 prevents histone 3 citrullination and neutrophil extracellular trap formation, and improves survival in a murine sepsis model
[4]
.
MCE 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. |
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]
.
MCE 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. |
Appearance
Solid
Shipping
Room temperature in continental US; may vary elsewhere.
Storage
-20°C, stored under nitrogen, away from moisture
* In solvent : -80°C, 6 months; -20°C, 1 month (stored under nitrogen, away from moisture)
Solvent & Solubility
DMSO : 50 mg/mL ( 143.99 mM ; Need ultrasonic)
H 2 O : 50 mg/mL ( 143.99 mM ; Need ultrasonic)
Stock Solutions
| Concentration Solvent Mass | 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 |
-
1.
Add each solvent one by one: PBS
Solubility: 5.5 mg/mL (15.84 mM); Clear solution; Need ultrasonic
-
2.
-
3.
Add each solvent one by one: 10% DMSO >> 90% (20% SBE-β-CD in saline)
Solubility: ≥ 1.25 mg/mL (3.60 mM); Clear solution
-
4.
Add each solvent one by one: 10% DMSO >> 90% corn oil
Solubility: ≥ 1.25 mg/mL (3.60 mM); Clear solution
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.
Synonyms