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MLN-1117
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。
MLN-1117图片
CAS NO:1268454-23-4
规格:≥98%
包装与价格:
包装价格(元)
2mg电议
5mg电议
10mg电议
25mg电议
50mg电议
100mg电议
250mg电议
500mg电议

产品介绍
理化性质和储存条件
Molecular Weight (MW) 363.37
Formula C19H17N5O3
CAS No. 1268454-23-4
Storage-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)DMSO:>15mg/mL (Need ultrasonic or warming)
Water: <1 mg/mL
Ethanol: <1 mg/mL
SMILES Code O=C(C1=CN=C2C=CC(C3=CC=C(OC(N)=N4)C4=C3)=CN21)N5CCOCC5
Synonyms Serabelisib; MLN 1117; MLN-1117; INK1117; INK-1117; INK 1117; MLN1117; TAK-117; TAK 117; TAK117
实验参考方法
In Vitro

In vitro activity: Serabelisib (also known as INK-1117, MLN-1117, and/or TAK-117) is a potent, selective, and oral bioavailable inhibitor of PI3Kα (phosphoinositide 3-kinase) isoform with IC50 of 21 nmol/L against PI3Kα. It exhibited> 100-fold selectivity relative to other class I PI3K family members (PI3Kβ/γ/δ) and mTOR, and a high degree of selectivity against many other kinase. Class IA PI3K is essential for clonal expansion, differentiation, and effector function of B and T lymphocytes. The p110δ catalytic isoform of PI3K is highly expressed in lymphocytes and plays a prominent role in B and T cell responses. Another class IA PI3K catalytic isoform, p110α, is a promising drug target in cancer but little is known about its function in lymphocytes. MLN1117 inhibits Akt phosphorylation and growth in PIK3CA mutant breast cancer cells with IC50s around 2 μM, yet has no effect on cells lacking PTEN. BCR-stimulated B cells treated with 1 μM MLN1117 displays a significant reduction (up to 50%) in the magnitude of the phosphorylated Akt (p-Akt) signal measured by intracellular flow cytometry. The effect of MLN1117 is dose-dependent


Kinase Assay: TAK-117 administration in PIK3CA-mutant tumor cell lines results in potent PI3K pathway inhibition, blockade of cellular proliferation, and apoptosis. INK1117 potently inhibits PI3K and demonstrates a greater than 100-fold selectivity relative to other class I PI3K family members and mTOR as well as a high degree of selectivity against a large panel of protein kinases. INK1117 blocks proliferation of tumor cell lines bearing PIK3CA mutations, and inhibits cellular phosphorylation and activity of AKT. However, INK1117 shows much less activity in PTEN-deficient tumor cells, which typically display constitutive PI3K pathway activation independent of PI3Kα.


Cell Assay: A total of 5000 SK-OV-3 and U87MG cell lines /well in low serum media (0.2% FBS) are seeded in triplicate wells of a 96-well flat bottom culture plate for 18 h to adhere. Media is aspirated and inhibitors in 0.2% FBS media are added to each well at the indicated concentrations. After 48 h, cell viability is determined using the MTS assay (Cell Titer 96 Aqueous One solution cell proliferation assay kit) with absorbance (490 nm) measured in a microplate spectrophotometer

In VivoIn mice, selective p110α inhibition using the investigational agent MLN1117 (previously known as INK1117) did not disrupt the marginal zone B cell compartment and did not block T cell-dependent germinal center formation. Treatment with MLN1117 at 30 and 60 mg/kg causes little reduction of TNP-specific IgG3. Notably, reduction of TNP-specific IgG3 at higher doses of MLN1117 (120 mg/kg) is observed, consistent with the partial reduction in cell division in B cells treated with MLN1117 before anti-IgM stimulation. However, 120 mg/kg is above the effective dose of MLN1117 for tumor growth inhibition (30-60 mg/kg)
Animal modelMice (C57BL/6)
Formulation & Dosage30 and 60 mg/kg; P.O.
References J Biol Chem. 2013 Feb 22;288(8):5718-31; PLoS One. 2014 Jun 10;9(6):e99486; Clin Cancer Res. 2017 Sep 1;23(17):5015-5023.