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PRN694 (PRN-694 ) is a novel, highly selective, irreversible/covalent dual inhibitor of interleukin-2-inducible T-cell kinase (ITK) and resting lymphocyte kinase (RLK) 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
| ln Vitro |
PRN694 has IC50 values of 3.3, 17, 17, 125, and 30 nM, respectively, for TEC, BTK, BMX, BLK, and JAK3 inhibition[1]. According to an immunoblot investigation of TCR activation pathways, PRN694 prevents NFAT1, JunB, pIκBα, and pERK from activating or moving to the nucleus. The findings show that PRN694 inhibits Ca2+ signaling at all doses higher than 1 nM. When PRN694 is added in quantities higher than 0.37 μM, it considerably reduces the death of NK cells caused by FcR[1]. Day 6 flow cytometry analysis shows that PRN694 significantly (p<0.01) suppresses the proliferation of both CD4 and CD8 T-cells produced by anti-CD3/CD28[1].
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| ln Vivo |
At 1, 6, and 14 hours, the PRN694 occupancy of ITK is 98, 95, and 54%, respectively. The plasma level of PRN694 at 14 hours is more than ten times lower than the whole blood IC50. Additionally, weights treated with RN694 are considerably lower than vehicle weights (p<0.05)[1]. ?Studies on colitis reveal that the colonic epithelium of mice treated with PRN694 has less CD4+ T cells than that of control mice[2].
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| References |
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| Molecular Formula |
C28H35F2N5O2S
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| Molecular Weight |
543.67
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| Exact Mass |
543.247
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| CAS # |
1575818-46-0
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| PubChem CID |
90044055
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| Appearance |
Off-white to light brown solid powder
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| Density |
1.3±0.1 g/cm3
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| Boiling Point |
679.8±65.0 °C at 760 mmHg
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| Flash Point |
364.9±34.3 °C
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| Vapour Pressure |
0.0±2.1 mmHg at 25°C
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| Index of Refraction |
1.619
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| LogP |
3.92
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
10
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| Heavy Atom Count |
38
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| Complexity |
856
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| Defined Atom Stereocenter Count |
2
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| SMILES |
C[C@@H](C(C)(C)C)NCC1=CC2=C(C=C1)N(C(=N2)NC(=O)C3=CC=C(S3)C(F)F)C[C@H]4CCCN4C(=O)C=C
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| InChi Key |
NXTKFBGDLDPFLB-PKOBYXMFSA-N
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| InChi Code |
InChI=1S/C28H35F2N5O2S/c1-6-24(36)34-13-7-8-19(34)16-35-21-10-9-18(15-31-17(2)28(3,4)5)14-20(21)32-27(35)33-26(37)23-12-11-22(38-23)25(29)30/h6,9-12,14,17,19,25,31H,1,7-8,13,15-16H2,2-5H3,(H,32,33,37)/t17-,19+/m0/s1
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| Chemical Name |
5-(difluoromethyl)-N-[5-[[[(2S)-3,3-dimethylbutan-2-yl]amino]methyl]-1-[[(2R)-1-prop-2-enoylpyrrolidin-2-yl]methyl]benzimidazol-2-yl]thiophene-2-carboxamide
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| Synonyms |
PRN 694 PRN-694 PRN694
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO : ~125 mg/mL (~229.92 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (3.83 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.08 mg/mL (3.83 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.08 mg/mL (3.83 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.8394 mL | 9.1968 mL | 18.3935 mL | |
| 5 mM | 0.3679 mL | 1.8394 mL | 3.6787 mL | |
| 10 mM | 0.1839 mL | 0.9197 mL | 1.8394 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution 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 stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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