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.
Physicochemical Properties
| Molecular Formula | C11H12N3O2SCL.2[HCL] |
| Molecular Weight | 358.67176 |
| Exact Mass | 356.987 |
| Elemental Analysis | C, 36.84; H, 3.93; Cl, 29.65; N, 11.72; O, 8.92; S, 8.94 |
| CAS # | 1177141-67-1 |
| Related CAS # | CKI-7 free base;120615-25-0 |
| PubChem CID | 16078955 |
| Appearance | Solid powder |
| LogP | 4.901 |
| Hydrogen Bond Donor Count | 4 |
| Hydrogen Bond Acceptor Count | 5 |
| Rotatable Bond Count | 4 |
| Heavy Atom Count | 20 |
| Complexity | 371 |
| Defined Atom Stereocenter Count | 0 |
| SMILES | C1=CC(=C2C=NC=CC2=C1Cl)S(=O)(=O)NCCN.Cl.Cl |
| InChi Key | JUAVTXYOCISSSL-UHFFFAOYSA-N |
| 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 |
| Chemical Name | N-(2-aminoethyl)-5-chloroisoquinoline-8-sulfonamide;dihydrochloride |
| Synonyms | CKI-7 2HCl; CKI 7 2HCl; CKI7 2HCl; CKI-7 dihydrochloride; CKI 7 dihydrochloride; CKI7 dihydrochloride |
| HS Tariff Code | 2934.99.9001 |
| 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) |
Biological Activity
| 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]. |
| 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]. |
| 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. |
| References |
[1]. In vitro differentiation of retinal cells from human pluripotent stem cells by small-molecule induction. J Cell Sci. 2009 Sep 1;122(Pt 17):3169-79. [2]. Small Molecule Inhibition of Cdc7, a Key Cell Cycle Regulator and Novel Therapeutic Target, Successfully Inhibits Leukemia Cell Growth in Vitro and in Vivo. Blood (2008) 112 (11): 2668. [3]. A newly synthesized selective casein kinase I inhibitor, N-(2-aminoethyl)-5-chloroisoquinoline-8-sulfonamide, and affinity purification of casein kinase I from bovine testis. J Biol Chem. 1989 Mar 25;264(9):4924-7. [4]. D4476, a cell-permeant inhibitor of CK1, suppresses the site-specific phosphorylation and nuclear exclusion of FOXO1a. EMBO Rep. 2004 Jan;5(1):60-5. |
Solubility Data
| 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 |
| 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 (e.g. IP/IV/IM/SC) Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline) *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). 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)] *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. Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline) Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline) Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline) Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil) Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL 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). Oral Formulation 3: Dissolved in PEG400 Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose Oral Formulation 6: Mixing with food powders Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently. (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 |