CKI-7
目录号 : GC38755
A CK1 inhibitor
Cas No.:120615-25-0
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >99.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
CKI-7 is an inhibitor of casein kinase 1 (CK1; Ki = 8.5 μM).1 It is selective for CK1 over CK2, PKC, CaM kinase II (CaMKII), and cyclic AMP-dependent protein kinase (IC50s = 90, >1,000, 195, and 550 μM, respectively). CKI-7 inhibits phosphorylation of a peptide substrate by Leishmania CK1.2 by 50% when used at a concentration of 10 μM.2
1.Chijiwa, T., Hagiwara, M., and Hidaka, H.A newly synthesized selective casein kinase I inhibitor, N-(2-aminoethyl)-5-chloroisoquinoline-8-sulfonamide, and affinity purification of casein kinase I from bovine testisJ. Biol. Chem.264(9)4924-4927(1989) 2.Rachidi, N., Taly, J.F., Durieu, E., et al.Pharmacological assessment defines Leishmania donovani casein kinase 1 as a drug target and reveals important functions in parasite viability and intracellular infectionAntimicrob. Agents Chemother.58(3)1501-1515(2014)
| Cas No. | 120615-25-0 | SDF | |
| Canonical SMILES | O=S(C1=CC=C(Cl)C2=C1C=NC=C2)(NCCN)=O | ||
| 分子式 | C11H12ClN3O2S | 分子量 | 285.75 |
| 溶解度 | DMSO: 25 mg/mL (87.49 mM) | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 3.4996 mL | 17.4978 mL | 34.9956 mL |
| 5 mM | 0.6999 mL | 3.4996 mL | 6.9991 mL |
| 10 mM | 0.35 mL | 1.7498 mL | 3.4996 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Isolation and characterization of human casein kinase I epsilon (CKI), a novel member of the CKI gene family
J Biol Chem 1995 Jun 23;270(25):14875-83.PMID:7797465DOI:10.1074/jbc.270.25.14875.
The casein kinase I (CKI) gene family is a rapidly enlarging group whose members have been implicated in the control of cytoplasmic and nuclear processes, including DNA replication and repair. We report here the cloning and characterization of a novel isoform of CKI from a human placental cDNA library. The cDNA for this isoform, hCKI epsilon, predicts a basic polypeptide of 416 amino acids and a molecular mass of 47.3 kDa. It encodes a core kinase domain of 285 amino acids and a carboxyl-terminal tail of 123 amino acids. The kinase domain is 53-98% identical to the kinase domains of other CKI family members and is most closely related to the delta isoform. Localization of the hCKI epsilon gene to chromosome 22q12-13 and the hCKI delta gene to chromosome 17q25 confirms that these are distinct genes in the CKI family. Northern blot analysis shows that hCKI epsilon is expressed in multiple human cell lines. Recombinant hCKI epsilon is an active enzyme that phosphorylates known CKI substrates including a CKI-specific peptide substrate and is inhibited by CKI-7, a CKI-specific inhibitor. A budding yeast isoform of CKI, HRR25, has been implicated in DNA repair responses. Expression of hCKI epsilon but not hCKI alpha rescued the slow-growth phenotype of a Saccharomyces cerevisiae strain with a deletion of HRR25. Human CKI epsilon is a novel CKI isoform with properties that overlap those of previously described CKI isoforms.
Crystallization and preliminary crystallographic analysis of 3'-aminoglycoside kinase type IIIa complexed with a eukaryotic protein kinase inhibitor, CKI-7
Acta Crystallogr D Biol Crystallogr 2004 Oct;60(Pt 10):1897-9.PMID:15388945DOI:10.1107/S0907444904019390.
3'-Aminoglycoside kinase type IIIa [APH(3')-IIIa] catalyzes the transfer of gamma-phosphate from ATP to the 3'-hydroxyl of many aminoglycoside antibiotics, abolishing their bactericidal effects. Despite very low sequence identity, APH(3')-IIIa and eukaryotic protein kinases share structural and functional similarities, including a sensitivity to isoquinolinsulfonamide-type inhibitors. APH(3')-IIIa has been cocrystallized with CKI-7, a casein kinase 1 inhibitor. These crystals were grown using PEG 3000 as precipitant and required consecutive cycles of microseeding. Data were collected to 2.5 A. The crystals belong to space group P2(1)2(1)2(1), with unit-cell parameters a = 49.84, b = 91.90, c = 131.2 A.
Bovine neurofilament-enriched preparations contain kinase activity similar to casein kinase I--neurofilament phosphorylation by casein kinase I (CKI)
Neurosci Lett 1993 Mar 5;151(1):89-93.PMID:8385762DOI:10.1016/0304-3940(93)90053-n.
Neurofilament (NF)-enriched preparations from bovine spinal cord contain regulator-independent kinase activities that phosphorylate NF subunits as well as alpha-casein. CKI-7 (N-2-amino ethyl, 5-chloroisoquinoline, 8-sulfonamide), a specific inhibitor of casein kinase I (CKI), inhibits the phosphorylation of NF subunits in the neurofilament preparation. This inhibition occurs at a concentration range identical to concentrations where CKI-7 inhibits rabbit reticulocyte CKI phosphorylation of alpha-casein. Heparin, a specific inhibitor of casein kinase II (CKII), produced only 20% inhibition of 32P incorporation into NF subunits, and only at concentrations 5 to 10-fold higher than those required to inhibit CKII from reticulocytes. CKI from rabbit reticulocytes phosphorylated all three NF subunits (NF-H, NF-M and NF-L). Comparison of the tryptic phosphopeptide maps of NF-M, phosphorylated by the NF-associated kinase and CKI, indicates that the casein kinase I phosphorylates many of the peptides phosphorylated by the NF-associated kinase and this phosphorylation occurs at the carboxy terminal tail domain of the NF-M subunit. These studies suggest that the major independent kinase activity associated with NFs is CKI.
H-7-induced apoptosis in the cells of a Drosophila neuronal cell line through affecting unidentified H-7-sensitive substance(s)
Neurosci Res 1998 Jun;31(2):113-21.PMID:9700717DOI:10.1016/s0168-0102(98)00030-3.
The present study was undertaken to reveal underlying mechanisms of apoptosis in neurons using clonal neuronal cells, ML-DmBG2-c2, derived from Drosophila larval central nervous system 1-(5-Isoquinolinesulfonyl)-2-methylpiperazine (H-7), a protein kinase inhibitor, induced cell death with typical features of apoptosis such as internucleosomal DNA fragmentation, nuclear condensation and apoptotic bodies in the cells. Though H-7 is known to inhibit cAMP-dependent protein kinase (PKA), protein kinase C (PKC), cGMP-dependent protein kinase (PKG), myosin light chain kinase (MLCK), and casein kinase I (CKI), specific inhibitors for these kinases such as H-89, calphostin C, ML-9, or CKI-7 did not induce apoptosis in the cells. Other kinases such as tyrosine kinase. PI3-kinase and Ca2+/CaM kinase II so far examined in the present study were interpreted not to be involved in the apoptotic cascade. Therefore, it is concluded that an H-7-sensitive substance(s) other than these kinases is responsible for the apoptosis in the neuronal cells. Caspase inhibitors prevented apoptosis in the cells treated with H-7. These results suggest that caspase(s) is involved downstream of the H-7-sensitive point in the cascade of the apoptosis.
Crystal structures of two aminoglycoside kinases bound with a eukaryotic protein kinase inhibitor
PLoS One 2011 May 9;6(5):e19589.PMID:21573013DOI:10.1371/journal.pone.0019589.
Antibiotic resistance is recognized as a growing healthcare problem. To address this issue, one strategy is to thwart the causal mechanism using an adjuvant in partner with the antibiotic. Aminoglycosides are a class of clinically important antibiotics used for the treatment of serious infections. Their usefulness has been compromised predominantly due to drug inactivation by aminoglycoside-modifying enzymes, such as aminoglycoside phosphotransferases or kinases. These kinases are structurally homologous to eukaryotic Ser/Thr and Tyr protein kinases and it has been shown that some can be inhibited by select protein kinase inhibitors. The aminoglycoside kinase, APH(3')-IIIa, can be inhibited by CKI-7, an ATP-competitive inhibitor for the casein kinase 1. We have determined that CKI-7 is also a moderate inhibitor for the atypical APH(9)-Ia. Here we present the crystal structures of CKI-7-bound APH(3')-IIIa and APH(9)-Ia, the first structures of a eukaryotic protein kinase inhibitor in complex with bacterial kinases. CKI-7 binds to the nucleotide-binding pocket of the enzymes and its binding alters the conformation of the nucleotide-binding loop, the segment homologous to the glycine-rich loop in eukaryotic protein kinases. Comparison of these structures with the CKI-7-bound casein kinase 1 reveals features in the binding pockets that are distinct in the bacterial kinases and could be exploited for the design of a bacterial kinase specific inhibitor. Our results provide evidence that an inhibitor for a subset of APHs can be developed in order to curtail resistance to aminoglycosides.