| Identification | Back Directory | [Name]
PRN694 | [CAS]
1575818-46-0 | [Synonyms]
PRN694
PRN694,PRN-694
(E)-N-(1-(((R)-1-Acryloylpyrrolidin-2-yl)methyl)-5-((((S)-3,3-dimethylbutan-2-yl)amino)methyl)
2-Thiophenecarboxamide, 5-(difluoromethyl)-N-[1-[[(2R)-1-(1-oxo-2-propen-1-yl)-2-pyrrolidinyl]methyl]-5-[[[(1S)-1,2,2-trimethylpropyl]amino]methyl]-1H-benzimidazol-2-yl]-
N-[(2E)-1-{[(2R)-1-Acryloyl-2-pyrrolidinyl]methyl}-5-({[(2S)-3,3-dimethyl-2-butanyl]amino}methyl)-1,3-dihydro-2H-benzimidazol-2-ylidene]-5-(difluoromethyl)-2-thiophenecarboxamide | [Molecular Formula]
C28H35F2N5O2S | [MDL Number]
MFCD28963888 | [MOL File]
1575818-46-0.mol | [Molecular Weight]
543.67 |
| Chemical Properties | Back Directory | [density ]
1.29±0.1 g/cm3(Predicted) | [storage temp. ]
Store at -20°C | [solubility ]
DMSO : 125 mg/mL (229.92 mM) | [form ]
Solid | [pka]
11.95±0.43(Predicted) | [color ]
Off-white to light brown |
| Hazard Information | Back Directory | [Uses]
PRN694 is an irreversible, highly selective and potent covalent interleukin-2-inducible T-cell kinase (ITK) and resting lymphocyte kinase (RLK) dual inhibitor with IC50s of 0.3 nM and 1.4 nM, respectively. PRN694 exhibits extended target residence time on ITK and RLK, enabling durable attenuation of effector cells in vitro and in vivo[1]. | [in vivo]
The PRN694 occupancy of ITK is 98, 95, and 54% at 1, 6, and 14 h, respectively. The concentrations of PRN694 in the plasma are 2.8, 0.66, and 0.027 μM at 1, 6, and 14 h, respectively. At 14 h, the plasma level of PRN694 is over 10 fold lower than the IC50 in whole blood. RN694 treatment also results in significantly lower weights relative to vehicle (p<0.05)[1].
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Colitis studies show reduced numbers of CD4+ T cells present in the colonic epithelium of PRN694-treated mice compare with controls[2]. | [References]
[1] Zhong Y, et al. Targeting interleukin-2-inducible T-cell kinase (ITK) and resting lymphocyte kinase (RLK) using a novel covalent inhibitor PRN694. J Biol Chem. 2015 Mar 6;290(10):5960-78. DOI:10.1074/jbc.M114.614891
[2] Cho HS, et al. A Small Molecule Inhibitor of ITK and RLK Impairs Th1 Differentiation and Prevents Colitis Disease Progression. J Immunol. 2015 Nov 15;195(10):4822-31. DOI:10.4049/jimmunol.1501828 |
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