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RepSox(SJN 2511)
本产品不向个人销售,仅用作科学研究,不用于任何人体实验及非科研性质的动物实验。
RepSox(SJN 2511)图片
CAS NO:446859-33-2
规格:≥98%
包装与价格:
包装价格(元)
10mg电议
25mg电议
50mg电议
100mg电议
250mg电议

产品介绍
理化性质和储存条件
Molecular Weight (MW)287.32
FormulaC17H13N5
CAS No.446859-33-2
Storage-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)DMSO: 57 mg/mL (198.4 mM)
Water: <1 mg/mL
Ethanol: <1 mg/mL
SMILES CodeCC1=CC=CC(C2=NNC=C2C3=NC4=CC=CN=C4C=C3)=N1
Synonyms

E-616452, SJN 2511; E 616452; E616452; RepSox; SJN-2511; SJN-2511; ALK5 Inhibitor II

Chemical Name: 2-[3-(6-methyl-2-pyridinyl)-1H-pyrazol-4-yl]-1,5-naphthyridine

Exact Mass: 287.1171

实验参考方法
In Vitro

In vitro activity: RepSox inhibits ATP binding to ALK5 and ALK5 autophosphorylation with IC50 of 23 nM and 4 nM, respectively. RepSox inhibits TGF-β induced cellular PAI-1 luciferase activity with IC50 of 18 NM. RepSox is able to successfully replace Sox2 in reprogramming by inhibiting transforming growth factor-β (Tgf-β) signaling, which in turn induces Nanog expression. Effect of RepSox inducing reprogramming does not require chromatin remodeling. RepSox is found to be efficient at generating iPSCs.


Kinase Assay: The kinase domain of ALK5 is cloned by PCR and expressed in a baculovirus/Sf9 cells system. The protein is 6-His tagged in the C terminus and purified by affinity chromatography using a Ni2+column, and the obtained material is used to assess compound activity in an autophosphorylation assay. Purified enzyme (10 nM) is incubated in 50 μL of Tris buffer (Tris 50 mM, pH 7.4; NaCl, 100 mM; MgCl2, 5 mM; MnCl2, 5 mM; and DTT, 10 mM). The enzyme is preincubated with different concentrations of RepSox (0.1% DMSO final concentration in the test) for 10 min at 37°C. The reaction is then initiated by the addition of 3 μM ATP (0.5 μCi γ-33P-ATP). After 15 min at 37°C, phosphorylation is stopped by the addition of SDS–PAGE sample buffer (50 mM Tris-HCl, pH 6.9, 2.5% glycerol, 1% SDS, and 5% β-mercaptoethanol). The samples are boiled for 5 min at 95°C and run on a 12% SDS–PAGE. Dried gels are exposed to a phosphor screen overnight. ALK5 autophosphorylation is quantified using a Storm imaging system.


Cell Assay: RepSox was found to replace the function of Sox2 to induce reprogramming of iPS cells, via the mechanism of inhibiting TGFβR-1. MEF cells were treated with RepSox for 3 days, and then it was removed at the time of transduction with Oct4, Klf4, and cMyc. The result showed the TGFβR-1 -associated expression of L-Myc was increased by 5-fold after RepSox treatment. A partially reprogrammed cell line (OKMS 6) was treated with RepSox and performed global gene expression analysis at 10, 24, and 48 hours following the initiation of treatment. The result showed the Id1, Id2 and Id3 gene, repressed by TGFβR-1 signaling, were released from that repression and the expression level was increased. Additionally, other genes responsive for TGFβR-1 signaling were inhibited. It suggested RepSox was able to inhibit TGFβR-1 and suppress the TGFβR-1 downstream signaling.

In VivoRepSox is able to be contribute to forming chimeric embryos in vivo when injected into blastocysts. A one-day treatment with RepSox is sufficient to replace transgenic Sox2.
Animal model
Formulation & Dosage
ReferencesJ Med Chem. 2004 Aug 26;47(18):4494-506; Cell Stem Cell. 2009 Nov 6; 5(5): 491–503.