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ChemicalBook--->CAS DataBase List--->1431698-10-0

1431698-10-0

1431698-10-0 Structure

1431698-10-0 Structure
IdentificationBack Directory
[Name]

OTSSP167HCL
[CAS]

1431698-10-0
[Synonyms]

OTSSP167HCL
OTS-167 hydrochloride
OTSSP167 HCl (OTS167 HCl)
MELK INHIBITOR; OTSSP-167; OTSSP 167
OTSSP167hydrochloride/OTSSP-167hydrochloride
1-[6-(3,5-Dichloro-4-hydroxyphenyl)-4-[[trans-4-[(dimethylamino)methyl]cyclohexyl]amino]-1,5-naphthyridin-3-yl]-ethanone hydrochloride
Ethanone,1-[6-(3,5-dichloro-4-hydroxyphenyl)-4-[[trans-4-[(dimethylamino)methyl]cyclohexyl]amino]-1,5-naphthyridin-3-yl]-,hydrochloride(1:1)
[Molecular Formula]

C25H29Cl3N4O2
[MDL Number]

MFCD25562907
[MOL File]

1431698-10-0.mol
[Molecular Weight]

523.882
Chemical PropertiesBack Directory
[storage temp. ]

Store at -20°C
[solubility ]

Soluble in DMSO
[form ]

crystalline solid
[color ]

Light yellow to gray
Safety DataBack Directory
[Symbol(GHS) ]


GHS05,GHS08,GHS07
[Signal word ]

Danger
Hazard InformationBack Directory
[Biological Activity]

otssp167 is an inhibitor of maternal embryonic leucine zipper kinase(melk) with ic50 value of 0.41nm [1].melk belongs to the ampk serine/threonine kinase family and involves in the mammalian embryonic development. it overexpresses in various types of human cancer. otssp167 is synthetized from a compound which is a hit of a high-throughput screening. in vitro anti-proliferative assay shows that otssp167 suppresses cell growth of various cancer cell lines, such as a549(ic50=6.7nm), t47d(ic50=4.3nm), du4475(ic50=2.3nm) and 22rv1(ic50= 6.0nm). in vivo assay also shows otssp167 can significantly suppress tumor growth in the xenograft model using various cancer cell lines. the effects are observed by both intravenous administration and oral administration. when investigating the substrates of melk, otssp167 is found to inhibit the phosphorylation of dbnl and psma1 in vitro. since psma1 is essential for survival of cancer cells, the reduction of phosphorylated psma1 caused by otssp167 can subsequently suppress mammosphere formation of cancer stem cells [1].
[in vitro]

OTSSP167 inhibits the growth of A549 (lung), T47D (breast), DU4475 (breast), 22Rv1 (prostate) and HT1197 (bladder) cancer cells with IC 50 values of 6.7 , 4.3, 2.3, 6.0 and 97 nM, respectively. It can abrogate the mitotic checkpoint, disrupt MCC and MCC-APC/C interaction in MCF7 cells, and causes GFP-MELK localization to cell cortex in prometaphase cells. OTSSP167 is a MELK selective inhibitor, exhibits a strong in vitro activity, conferring an IC 50 of 0.41 nM.

[in vivo]

OTSSP167 (20 mg/kg, iv) results in tumor growth inhibition (TGI) of 73% in xenograft mouse model; OTSSP167 (1, 5, and 10 mg/kg, po) reveals TGI of 51, 91, and 108%, respectively. OTSSP167 (20 mg/kg, po) shows no tumor growth suppressive effect on PC-14 xenografts.

[target]

IC50: 0.41 nM (MELK)

[References]

[1] suyoun chung, hanae suzuki, takashi miyamoto et al. development of an orally-administrative melk-targeting inhibitor that suppresses the growth of various types of human cancer. oncotarget. 2012, 3: 1629-1640.
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