CKI-7 HCl

Names

[ Name ]:
CKI-7 HCl

[Synonym ]:
N-(2-Aminoethyl)-5-chloroisoquinoline-8-sulphonamide dihydrochloride
CKI-7 dihydrochloride
N-(2-Aminoethyl)-5-chloro-8-isoquinolinesulfonamide dihydrochlori de

Biological Activity

[Description]:

CKI-7 is a potent and ATP-competitive casein kinase 1 (CK1) inhibitor with an IC50 of 6 μM and a Ki of 8.5 μM. CKI-7 is a selective Cdc7 kinase inhibitor. CKI-7 also inhibits SGK, ribosomal S6 kinase-1 (S6K1) and mitogen- and stress-activated protein kinase-1 (MSK1). CKI-7 has a much weaker effect on casein kinase II and other protein kinases[1][2][3][4].

[Related Catalog]:

Research Areas >> Cancer

Signaling Pathways >> Metabolic Enzyme/Protease >> SGK

Signaling Pathways >> Cell Cycle/DNA Damage >> CDK

Signaling Pathways >> Cell Cycle/DNA Damage >> Casein Kinase

Signaling Pathways >> MAPK/ERK Pathway >> Ribosomal S6 Kinase (RSK)

Signaling Pathways >> Stem Cell/Wnt >> Casein Kinase

[Target]

CK1:6 μM (IC50)

CK1:8.5 μM (Ki)

Cdc7

SGK

S6K1

MSK1

[In Vitro]

CKI-7 (0.1-10 μM; 5 days; ES cells) treatment significantly increases the expression of the early neuroectodermal marker Sox1 and the number of cells positive for the neural markers nestin and βIII-tubulin, in a concentration-dependent manner[1]. CKI-7 (5 μM; 5 days; ES cells) treatment suppresses SFEB-induced β-catenin stabilization on day 5, indicating that CKI-7 inhibits Wnt signaling[1]. RT-PCR[1] Cell Line: Mouse ES cells Concentration: 0.1-10 μM Incubation Time: 5 days Result: Significantly increased the expression of the early neuroectodermal marker Sox1 and the number of cells positive for the neural markers nestin and βIII-tubulin, in a concentration-dependent manner. Western Blot Analysis[1] Cell Line: Mouse ES cells Concentration: 5 μM Incubation Time: 5 days Result: Suppressed SFEB-induced β-catenin stabilization on day 5.

[In Vivo]

In vivo dose-dependent anti-tumor activity of CKI-7 is demonstrated in a SCID-Beige mouse systemic tumor model utilzing a recently isolated Philadelphia chromosome positive acute lymphoblastic leukemia cell line. Standard cell cycle synchronization studies established that exposure to CKI-7 results in cell cycle dependent caspase 3 activation and apoptotic cell death[2].

[References]

[1]. Osakada F, et al. 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]. Mark G. Frattini, et al. 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]. Chijiwa T, et al. 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]. Rena G, et al. 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.

Chemical & Physical Properties

[ Molecular Formula ]:
C₁₁H₁₄Cl₃N₃O₂S

[ Molecular Weight ]:
358.67200

[ Exact Mass ]:
356.98700

[ PSA ]:
93.46000

[ LogP ]:
4.90120

[ Storage condition ]:
-20°C

MSDS

Click to get detail MSDS

Safety Information

[ Symbol ]:

GHS06

[ Signal Word ]:
Danger

[ Hazard Statements ]:
H301

[ Precautionary Statements ]:
P301 + P310

[ Personal Protective Equipment ]:
Eyeshields;Faceshields;Gloves;type P2 (EN 143) respirator cartridges

[ Hazard Codes ]:
T+

[ RIDADR ]:
UN 2811 6.1 / PGIII

[ Hazard Class ]:
6.1

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