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Purity: ≥98%
CKI-7 2HCl is a novel, potent and ATP-competitive casein kinase 1 (CK1) inhibitor with an IC50 of 6 μM and a Ki of 8.5 μM. Moreover, CKI-7 suppresses mitogen- and stress-activated protein kinase-1 (MSK1), ribosomal S6 kinase-1 (S6K1), and SGK. Regarding casein kinase II and other protein kinases, CKI-7 has a substantially lesser impact.
| Targets |
CKI-7 is reported to be an inhibitor of casein kinase 1 (CK1). (IC₅₀ = 6 µM against CK1δ at an ATP concentration of 0.1 mM in vitro.) [3]
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| ln Vitro |
In ES cells, CKI-7 treatment (0.1-10 μM; 5 days) dramatically enhanced the number of cells positive for the neural markers βIII-tubulin and nestin, as well as the expression of the early neuroectoderm marker Sox1 in a concentration-dependent manner [1]. Day 5 β-catenin stabilization induced by SFEB was decreased by CKI-7 (5 μM; 5 days; ES cells) treatment, suggesting that CKI-7 suppresses Wnt signaling [1].
In a comparative in vitro kinase assay, CKI-7 inhibited CK1δ with an IC₅₀ of 6 µM at an ATP concentration of 0.1 mM. This IC₅₀ value was approximately 20-fold higher than that of the inhibitor D4476 tested under the same conditions. [3] Importantly, CKI-7 lacked specificity for CK1. At the concentration tested (0.1 mM ATP), it was found to inhibit serum and glucocorticoid-induced kinase (SGK) as potently as CK1. Additionally, several other protein kinases, such as ribosomal S6 kinase-1 (S6K1) and mitogen- and stress-activated protein kinase-1 (MSK1), were inhibited almost as strongly. [3] In a cellular context using H4IIE hepatoma cells, CKI-7 had no detectable effect on the insulin-induced phosphorylation of FOXO1a at Ser322 or Ser325, even at concentrations as high as 0.3 mM. This lack of cellular efficacy, despite in vitro activity, is attributed to its ATP-competitive nature and the much higher intracellular ATP concentrations, coupled with its lower potency compared to D4476. [3] |
| ln Vivo |
Using a newly isolated Philadelphia chromosome-positive acute lymphoblastic leukemia cell line, the in vivo dose-dependent antitumor activity of CKI-7 was demonstrated in a SCID-Beige mouse systemic tumor model. The activation of caspase 3 and subsequent cell cycle-dependent apoptosis are confirmed by standard cell cycle synchronization studies upon exposure to CKI-7 [2].
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| Enzyme Assay |
The inhibitory activity of CKI-7 against CK1 was assessed in an in vitro kinase assay. Purified CK1δ enzyme was assayed using a phosphorylated peptide substrate (TFRPRTSpSNASTIS, 30 µM) corresponding to residues 312–325 of FOXO1a. The assay was performed at 30°C with an ATP concentration of 0.1 mM in the presence of varying concentrations of CKI-7. Kinase activity was measured, and the IC₅₀ value was determined by plotting the percentage of remaining activity against the inhibitor concentration. Its effects on other kinases (SGK, S6K1, MSK1) were evaluated in similar assay formats against their respective substrates. [3]
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| Cell Assay |
RT-PCR[1]
Cell Types: Mouse ES cells Tested Concentrations: 0.1-10 μM Incubation Duration: 5 days Experimental Results: The expression of early neuroectoderm marker Sox1 was Dramatically increased, and the neural markers nestin and βIII-tubulin were Dramatically increased. The number of positive cells increased Dramatically in a concentration-dependent manner. Western Blot Analysis[1] Cell Types: Mouse ES cells Tested Concentrations: 5 μM Incubation Duration: 5 days Experimental Results: Inhibition of SFEB-induced β-catenin stabilization on day 5. The effect of CKI-7 on site-specific phosphorylation in cells was evaluated in H4IIE hepatoma cells. Cells were serum-starved and then stimulated with insulin (20 nM) for 30 minutes to induce phosphorylation of FOXO1a. Where indicated, cells were pre-incubated with CKI-7 (at concentrations up to 0.3 mM) for a specified period before stimulation. After treatment, cells were lysed, and endogenous FOXO1a was immunoprecipitated from the lysates. The immunoprecipitates were then denatured, subjected to SDS-PAGE, and transferred to nitrocellulose membranes. Phosphorylation at specific sites (Ser322 and Ser325) was assessed by immunoblotting using phospho-specific antibodies. [3] |
| References |
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| Additional Infomation |
CKI-7 (N-(2-aminoethyl)-5-chloroisoquinoline-8-sulfonamide) was initially synthesized and reported as a selective CK1 inhibitor. However, this study highlights its lack of selectivity, as its inhibitory efficacy against several other kinases is also similar. [3] In this study, CKI-7 was primarily used as a reference compound for comparison with the novel inhibitor D4476. Due to its poor cellular activity and lack of specificity, the authors concluded that D4476 is a better tool for studying intracellular CK1 biology. [3]
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| Molecular Formula |
C11H12N3O2SCL.2[HCL]
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| Molecular Weight |
358.67176
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| Exact Mass |
356.987
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| Elemental Analysis |
C, 36.84; H, 3.93; Cl, 29.65; N, 11.72; O, 8.92; S, 8.94
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| CAS # |
1177141-67-1
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| Related CAS # |
CKI-7 free base;120615-25-0
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| PubChem CID |
16078955
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| Appearance |
Solid powder
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| LogP |
4.901
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| Hydrogen Bond Donor Count |
4
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
20
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| Complexity |
371
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C1=CC(=C2C=NC=CC2=C1Cl)S(=O)(=O)NCCN.Cl.Cl
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| InChi Key |
JUAVTXYOCISSSL-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C11H12ClN3O2S.2ClH/c12-10-1-2-11(18(16,17)15-6-4-13)9-7-14-5-3-8(9)10;;/h1-3,5,7,15H,4,6,13H2;2*1H
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| Chemical Name |
N-(2-aminoethyl)-5-chloroisoquinoline-8-sulfonamide;dihydrochloride
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| Synonyms |
CKI-7 2HCl; CKI 7 2HCl; CKI7 2HCl; CKI-7 dihydrochloride; CKI 7 dihydrochloride; CKI7 dihydrochloride
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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) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.7881 mL | 13.9404 mL | 27.8808 mL | |
| 5 mM | 0.5576 mL | 2.7881 mL | 5.5762 mL | |
| 10 mM | 0.2788 mL | 1.3940 mL | 2.7881 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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