312636-16-1 Usage
Description
SKI II is a nonlipid inhibitor of sphingosine kinase, which is orally bioavailable and has demonstrated significant inhibition of tumor growth in mice.
Uses
Used in Pharmaceutical Industry:
SKI II is used as an anticancer agent for its ability to inhibit tumor growth in mice. Its nonlipid nature and oral bioavailability make it a promising candidate for the development of cancer treatments.
Biological Activity
Selective non-lipid inhibitor of sphingosine kinase (IC 50 = 0.5 μ M); does not act at ATP-binding site. Displays no inhibition of ERK2, PI 3-kinase, or PKC α at concentrations up to 60 μ M. Reduces levels of sphingosine-1-phosphate in MDA-MB-231 breast cancer cells. Induces apoptosis and inhibits proliferation in several other tumor cell lines in vitro (IC 50 = 0.9-4.6 μ M).
Biochem/physiol Actions
Sphingosine kinase (SK) plays a pivotal role in regulating tumor growth and SK can act as an oncogene. Expression of SK RNA is significantly elevated in a variety of solid tumors, compared with normal tissue from the same patient. A number of novel inhibitors of human SK were identified, and several representative compounds were characterized in detail. These compounds demonstrated activity at sub- to micromolar concentrations, making them more potent than any other reported SK inhibitor, and were selective toward SK compared with a panel of human lipid and protein kinases. Kinetic studies revealed that the compounds were not competitive inhibitors of the ATP-binding site of SK. 4-[4-(4-chloro-phenyl)-thiazol-2-ylamino]-phenol (SKI-II) inhibitor is orally bioavailable, detected in the blood for at least 8 h, and showed a significant inhibition of tumor growth in mice with IC50 = 0.5 μM; SKI II does not act at ATP-binding site. Displays no inhibition of ERK2, PI 3-kinase, or PKCa at concentrations up to 60 μM.SKI II induces apoptosis and inhibits proliferation in several other tumor cell lines in vitro (IC50 = 0.9-4.6 μM).
references
[1] french kj, schrecengost rs, lee bd, zhuang y, smith sn, eberly jl, yun jk, smith cd. discovery and evaluation of inhibitors of human sphingosine kinase. cancer res. 2003 sep 15;63(18):5962-9.
Check Digit Verification of cas no
The CAS Registry Mumber 312636-16-1 includes 9 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 6 digits, 3,1,2,6,3 and 6 respectively; the second part has 2 digits, 1 and 6 respectively.
Calculate Digit Verification of CAS Registry Number 312636-16:
(8*3)+(7*1)+(6*2)+(5*6)+(4*3)+(3*6)+(2*1)+(1*6)=111
111 % 10 = 1
So 312636-16-1 is a valid CAS Registry Number.
InChI:InChI=1/C15H11ClN2OS/c16-11-3-1-10(2-4-11)14-9-20-15(18-14)17-12-5-7-13(19)8-6-12/h1-9,19H,(H,17,18)
312636-16-1Relevant articles and documents
Synthesis and Biological Evaluation of N-aryl-4-aryl-1,3-Thiazole-2-Amine Derivatives as Direct 5-Lipoxygenase Inhibitors
Suh, Jeehee,Yum, Eul Kgun,Cheon, Hyae Gyeong,Cho, Young Sik
experimental part, p. 89 - 98 (2012/08/29)
Biological evaluation of N-aryl-4-aryl-1,3-thiazole-2-amine derivatives was examined for anti-inflammatory activity in in vitro and in vivo assays. The thiazole compounds showed direct inhibition of 5-lipoxygenase (LOX) that is a key enzyme of leukotrienes synthesis and involved in the inflammation-related diseases, including asthma and rheumatoid arthritis. To optimize biological activity, we synthesized 1,3-thiazole-2-amine derivatives and investigated for structure and activity relationship. Especially, N-(3,5-dimethylphenyl)-4-(4-chlorophenyl)-1,3-thiazole-2-amine was shown to have a potent anti-inflammatory activity as a 5-LOX inhibitor.
