| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 25mg |
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| 50mg |
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KI-696 (KI696) is a novel and high affinity chemical probe for KEAP1 with the potential to be used for diseases involving oxidative stress. It is a potent inhibitor that can disrupt the KEAP1/NRF2 protein-protein interaction. KI-696 represents an excellent probe to study the KEAP1-NRF2 interaction in vivo. Discovered by FBS, the probe is well characterised in a number of in vitro assays as well as showing robust in vivo effects. The in vivo application is hampered by low bioavailability and high clearance, necessitating IV infusions as the mode of administration, which may limit the usefulness of the probe in vivo.
| ln Vitro |
Compound 7, KI696, has a very high affinity for the KEAP1 Kelch domain (ITC Kd=1.3 nM). No significant cross-reactivity is seen with the exception of the organic anion transporting polypeptide 1B1 (OATP1B1) (IC50=2.5 µM), the bile salt export pump BSEP (IC50=4.0 µM), and the phosphodiesterase PDE3A (IC50=10 µM). At dosages up to 10 µM, KI696 does not exhibit any cytotoxicity toward BEAS-2B cells. In normal human bronchial epithelial cells, KI696 stimulates NRF2 nuclear translocation. In non-targeting siRNA-transfected NHBE cells, KI696 enhances the mRNA expression of the NRF2-dependent genes NQO1 and GCLM, whereas compound activity is markedly reduced by NRF2 gene silencing. In a manner that is dependent on NRF2, KI696 raises NQO1 Activity. While pre-treating cells with 1 µM KI696 prior to exposure to tBHP preserved cell shape consistent with the DMSO control, treatment with tBHP obviously had a deleterious effect on cell health and appearance. In bronchial epithelial cells obtained from COPD patients, KI696 Induces the Expression of NRF2-Regulated Genes [1].
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| ln Vivo |
KI696 promotes the expression of each of the Nqo1, Ho-1, Txnrd1, Srxn1, Gsta3, Gclc genes in a dosage-dependent manner, with maximum increases over vehicle controls of 37-(Nqo1), 17-(Ho-1), 9-(Txnrd1), 28-(Srxn1), 15-(Gsta3) and 13-fold (Gclc) occurring at the 50 µmol/kg dose. EC50 readings are 44.0, 25.7, 42.6, 33.8, 28.4, and 44.1 µmol/ kilogram, respectively, yielding an average EC50 value of 36.4±3.4 µmol/kg. KI696 attenuates ozone-Induced lung inflammation. KI696 reverses ozone-induced reduction of lung GSH levels. KI696 is delivered to rats at 10, 35 and 50 µmol/kg via IV infusion, resulting in steady state chemical concentrations in the blood of 407±44 nM, 946±50 nM and 1437±186 nM, respectively, over the 6 hour infusion period. Exposure to ozone 24 hours post-dose generates a considerable reduction in lung levels of the anti-oxidant molecule, GSH, which is recovered by KI696 in a dose-dependent manner[1].
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| References |
| Molecular Formula |
C28H30N4O6S
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|---|---|
| Molecular Weight |
550.626005649567
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| Exact Mass |
550.188
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| CAS # |
1799974-70-1
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| PubChem CID |
118170767
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| Appearance |
White to off-white solid powder
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| LogP |
3.5
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
9
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| Rotatable Bond Count |
7
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| Heavy Atom Count |
39
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| Complexity |
962
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| Defined Atom Stereocenter Count |
2
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| SMILES |
S1(C2C=CC=CC=2O[C@H](C)CN1CC1C(C)=CC=C(C=1)[C@H](CC(=O)O)C1C=C(C2=C(C=1)N=NN2C)OC)(=O)=O
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| InChi Key |
ZDNGJXBUEQNFBQ-GCJKJVERSA-N
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| InChi Code |
InChI=1S/C28H30N4O6S/c1-17-9-10-19(22(14-27(33)34)20-12-23-28(25(13-20)37-4)31(3)30-29-23)11-21(17)16-32-15-18(2)38-24-7-5-6-8-26(24)39(32,35)36/h5-13,18,22H,14-16H2,1-4H3,(H,33,34)/t18-,22+/m1/s1
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| Chemical Name |
(S)-3-(7-methoxy-1-methyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(4-methyl-3-(((R)-4-methyl-1,1-dioxido-3,4-dihydro-2H-benzo[b][1,4,5]oxathiazepin-2-yl)methyl)phenyl)propanoic
acid
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| Synonyms |
KI696 KI 696 KI-696
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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 : ~50 mg/mL (~90.81 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: 2.5 mg/mL (4.54 mM) in 5% DMSO + 40% PEG300 + 5% Tween80 + 50% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication.
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 (3.78 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.8161 mL | 9.0805 mL | 18.1610 mL | |
| 5 mM | 0.3632 mL | 1.8161 mL | 3.6322 mL | |
| 10 mM | 0.1816 mL | 0.9081 mL | 1.8161 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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