| CAS |
No.1221186-53-3 |
| 英文名称 |
TEPP-46 |
| 别名 |
TEPP-46 |
| 分子式 |
C17H16N4O2S2 |
| 分子量 |
372.46 |
| 溶解性 |
Soluble in DMSO |
| 外观(性状) |
White to yellow Solid |
| 储存条件 |
Powder:2-8℃，2 years;Insolvent(母液):-20℃，6 months;-80℃，1 year |
| MDL |
MFCD23160747 |
| SMILES |
O=C1C(N(C)C2=C3SC(S(C)=O)=C2)=C3C=NN1CC4=CC=CC(N)=C4 |
| 靶点 |
Pyruvate Kinase |
| 通路 |
Metabolic Enzyme&Protease |
| 背景说明 |
TEPP-46/mL-265是丙酮酸激酶M2(PKM2)的新型有效选择性小分子激活剂。 |
| 生物活性 |
TEPP-46 (ML-265) is a potent and selective pyruvate kinase M2 (PKM2) activator with an AC50 of 92 nM， showing little or no effect on PKM1， PKL and PKR.[1-2] |
| In Vitro |
TEPP-46 and DASA-58 activate PKM2 by a mechanism similar to that of the endogenous activator FBP. Pre-treatment of cells with TEPP-46 or DASA-58 prevents pervanadate-induced inhibition of PKM2 activity. TEPP-46 also induces a decrease in the intracellular levels of acetyl-coA， lactate， ribose phosphate and serine[1]. TEPP-46 inhibits LPS-induced Hif-1α and IL-1β， as well as the expression of a range of other Hif-1α-dependent genes. TEPP-46 treatment significantly downregulates the expression of the M1 markers Il12p40 and Cxcl-10. Activation of PKM2 using TEPP-46 significantly inhibits FSL-1 and CpG-induced Il1b mRNA expression. TEPP-46 inhibits Mtb-induced Il1b mRNA levels， boosts Mtb-induced levels of Il10 mRNA， and has no effect on levels of Tnf[2]. |
| In Vivo |
TEPP-46 exhibits good oral bioavailability with relatively low clearance， long half-life， and good volume of distribution-parameters that predict for drug exposure in tumor tissues. TEPP-46 at 150 mg/kg readily achieves maximal PKM2 activation measured in A549 xenograft tumors[1]. |
| 细胞实验 |
2，000 cells are seeded in 96-well plates 24 h prior to treatment start. CellTiter96? AQueous is used to assess cell viability following oxidant and PKM2 activator combination treatments. MTS: (3-(4，5-dimethylthiazol-2-yl)-5- (3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium).[1-2] |
| 动物实验 |
H1299 parental and H1299 cells with constitutive expression of a mouse PKM1 cDNA (H1299-PKM1 cells) are propagated in RPMI supplemented with 10% fetal bovine serum， 2 mM glutamine， and hygromycin for transgene selection. Cells are harvested， resuspended in sterile PBS， and 5×105 cells are injected subcutaneously into nu/nu mice. Tumor growth is monitored by caliper measurement， the mice are sacrificed and tumors harvested after the time indicated. Tumors are weighed， divided and either flash-frozen in liquid nitrogen or fixed in formalin for later analysis.[1-2] |
| 数据来源文献 |
[1]. Anastasiou D， et al. Pyruvate kinase M2 activators promote tetramer formation and suppress tumorigenesis. Nat Chem Biol. 2012 Oct;8(10):839-847.
[2]. Palsson-McDermott EM， et al. Pyruvate kinase M2 regulates Hif-1α activity and IL-1β induction and is a critical determinant of the warburg effect in LPS-activated macrophages. Cell Metab. 2015 Jan 6;21(1):65-80. |
| 规格 |
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| 单位 |
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