| Identification | Back Directory | [Name]
BB-Cl-Amidine | [CAS]
1802637-39-3 | [Synonyms]
CS-2826
BB-Cl-Amidine
N-{(1S)-1-(1H-Benzimidazol-2-yl)-4-[(2-chloroethanimidoyl)amino]butyl}-4-biphenylcarboxamide
[1,1'-Biphenyl]-4-carboxamide, N-[(1S)-1-(1H-benzimidazol-2-yl)-4-[(2-chloro-1-iminoethyl)amino]butyl]- | [Molecular Formula]
C26H26ClN5O | [MDL Number]
MFCD31746879 | [MOL File]
1802637-39-3.mol | [Molecular Weight]
459.97 |
| Chemical Properties | Back Directory | [storage temp. ]
Inert atmosphere,Store in freezer, under -20°C | [solubility ]
DMSO:76.33(Max Conc. mg/mL);165.94(Max Conc. mM)
DMF:20.0(Max Conc. mg/mL);43.48(Max Conc. mM)
Water:70.0(Max Conc. mg/mL);152.18(Max Conc. mM)
Ethanol:54.5(Max Conc. mg/mL);118.48(Max Conc. mM)
Ethanol:PBS (pH 7.2) (1:1):0.5(Max Conc. mg/mL);1.09(Max Conc. mM) | [form ]
A crystalline solid | [color ]
white to beige | [InChIKey]
YDOAWJHYHGBQFI-QHCPKHFHSA-N | [SMILES]
C1(C2=CC=CC=C2)=CC=C(C(N[C@H](C2NC3=CC=CC=C3N=2)CCCNC(=N)CCl)=O)C=C1 |
| Hazard Information | Back Directory | [Description]
BB-Cl-Amidine is a modified version of Cl-amidine that retains the functional components but possesses a C-terminal benzimidazole group designed to limit proteolysis of the C-terminal amide. BB-Cl-Amidine irreversibly inactivates all four PAD subtypes (kinact/KI = 16,100, 4,100, 6,800, and 13,300 M-1min-1 for PAD1-4, respectively) by covalently modifying an active site cysteine that is important for its catalytic activity. The cellular potency of BB-Cl-amidine against PAD4 is increased 20-fold over the parent compound (EC50 = 8.8 μM versus >200 μM for Cl-amidine). BB-Cl-Amidine also has a significantly longer in vivo half-life than Cl-amidine (1.75 h versus ~15 min, respectively). Both compounds inhibit the formation of neutrophil extracellular traps without altering H2O2 production by neutrophils. BB-Cl-Amidine is effective in vivo, improving endothelial function while downregulating the expression of type I interferon-regulated genes in MRL/lpr mice. | [Uses]
BB-Cl-Amidine is a peptidylarginine deminase (PAD) inhibitor. | [in vivo]
Treatment with BB-Cl-amidine subtly reduces splenomegaly in MRL/lpr mice, while there is a trend towards increased circulating levels of anti-NET antibodies with PAD inhibitor treatment. However, neither PAD inhibitor affected body weight or total IgG levels. Indeed, treatment with both Cl-amidine and BB-Cl-amidine significantly improves endothelium-dependent vasorelaxation. The BB-Cl-amidine group also shows a strong trend towards downregulation of IRGs. Treatment with either Cl-amidine or BB-Cl-amidine significantly improves muzzle alopecia, in many cases preventing it entirely[1]. | Animal Model: | MRL/lpr mice[1].
| | Dosage: | 1 mg/kg. | | Administration: | Subcutaneous injection daily from 8 to 14 weeks of age. | | Result: | Significantly improved endothelium-dependent vasorelaxation and showed a strong trend towards downregulation of IRGs. |
| [References]
[1] Knight JS, et al. Peptidylarginine deiminase inhibition disrupts NET formation and protects against kidney, skin and vascular disease in lupus-prone MRL/lpr mice. Ann Rheum Dis. 2015 Dec;74(12):2199-206. DOI:10.1136/annrheumdis-2014-205365 |
|
| Company Name: |
Cckinase, Inc.
|
| Tel: |
+1 (732)236-3202 |
| Website: |
www.cckinase.com |
|