603288-22-8 Usage
Description
LY2090314 is a novel compound that functions as a glycogen synthase kinase-3α (GSK-3α) inhibitor. It is designed to target and inhibit the activity of GSK-3α, which plays a crucial role in various cellular processes, including cell growth, differentiation, and apoptosis. By inhibiting GSK-3α, LY2090314 has the potential to modulate these processes and exhibit therapeutic effects in certain conditions.
Uses
Used in Pharmaceutical Industry:
LY2090314 is used as a therapeutic agent for the treatment of acute myeloid leukemia (AML). It targets the GSK-3α enzyme, which is involved in the regulation of cell growth and differentiation. In AML, the inhibition of GSK-3α by LY2090314 can help control the uncontrolled proliferation of leukemia cells and potentially lead to the remission of the disease.
Additionally, due to its mechanism of action, LY2090314 may also have potential applications in other cancer types or conditions where GSK-3α plays a significant role. However, further research and clinical trials would be necessary to establish its efficacy and safety in these contexts.
Biological Activity
ly2090314 (ly) is a potent inhibitor of glycogen synthase kinase-3 (gsk-3) which plays an important role in various pathways, such as protein synthesis initiation, cell proliferation/differentiation, and apoptosis.
Biochem/physiol Actions
LY2090314 is a potent and selective ATP-competitive inhibitor of Glycogen synthase kinase-3 (GSK-3) currently in clinical trials for cancer therapy. LY2090314 has IC50 values of 1.5 nM and 0.9 nM for GSK-3α and GSK-3β, respectively.
in vitro
ly2090314 selectively inhibits the activity of gsk-3 by inhibiting atp binding. ly2090314 was reported to be able to stabilize β-catenin. as monotherapy, ly2090314 aslso showed limited efficacy. in solid tumor cancer cell lines, ly3090314 was found to enhance the efficacy of cisplatin and carboplatin [1].
in vivo
even in mdr1a-, bcrp-, and mrp2-knockout rats, the metabolites of ly2090314 did not appear in systemic circulation, and the urinary excretion was not found to be enhanced, since the hypothesized impaired biliary excretion of metabolites in the absence of these canalicular transporters was not observed. dog metabolite disposition was similar, with the exception of ly2090314 glucuronide. moreover, ly2090314 enhances the efficacy of cisplatin and carboplatin in solid tumor cancer xenografts [1]
IC 50
1.5 nm (gsk-3α); 0.9 nm (gsk-3β)
references
[1] brail lh, et al. j clin oncol, 2011, 29, abstr 3030.
Check Digit Verification of cas no
The CAS Registry Mumber 603288-22-8 includes 9 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 6 digits, 6,0,3,2,8 and 8 respectively; the second part has 2 digits, 2 and 2 respectively.
Calculate Digit Verification of CAS Registry Number 603288-22:
(8*6)+(7*0)+(6*3)+(5*2)+(4*8)+(3*8)+(2*2)+(1*2)=138
138 % 10 = 8
So 603288-22-8 is a valid CAS Registry Number.
603288-22-8Relevant articles and documents
Pictet-Spengler based synthesis of a bisarylmaleimide glycogen synthase kinase-3 inhibitor
Magnus, Nicholas A.,Ley, Christopher P.,Pollock, Patrick M.,Wepsiec, James P.
, p. 3700 - 3703 (2010)
A practical synthesis of the glycogen synthase kinase-3 (GSK3) inhibitor bisarylmaleimide 1 has been accomplished employing Pictet-Spengler methodology to access the indole 7-position in preparing the benzodiazepine tricyclic fragment. A seven-step linear sequence that starts with commercially available 5-fluoroindole 7 affords the bisarylmaleimide 1 in 33% overall yield.
HEMATOPOIETIC NEOPLASM CHEMOTHERAPY
-
, (2010/11/03)
A method and medicament for treating mixed lineage leukemia; translocated mixed lineage leukemia; translocated mixed lineage leukemia based acute myelogenous leukemia; translocated mixed lineage leukemia based acute lymphoid leukemia; a non-MLL based chronic myeloproliferative disorder, or non-MLL based acute lymphoid leukemia is provided.
