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TEPP-46(ML-265)
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。
TEPP-46(ML-265)图片
CAS NO:1221186-53-3
规格:≥98%
包装与价格:
包装价格(元)
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) 372.46
Formula C17H16N4O2S2
CAS No. 1221186-53-3
Storage-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)DMSO: ≥ 50mg/mL
Water: N/A
Ethanol: N/A
Chemical Name 6-(3-aminobenzyl)-4-methyl-2-(methylsulfinyl)-4,6-dihydro-5H-thieno[2',3':4,5]pyrrolo[2,3-d]pyridazin-5-one
Synonyms TEPP46; CID 44246499; NCGC00186528; TEPP 46; ML 265; CID44246499; TEPP-46; ML265; ML-265; CID-44246499; NCGC 00186528; NCGC-00186528;
实验参考方法
In Vitro

In vitro activity: TEPP-46 is a novel potent and selective small molecule activator of pyruvate kinase M2 (PKM2) with an EC50 of 92 nM, it showed little or no effect on PKM1, PKL and PKR. Macrophages activated by the TLR4 agonist LPS undergo dramatic changes in their metabolic activity. LPS induces expression of the key metabolic regulator Pyruvate Kinase M2 (PKM2). Activation of PKM2 using the well-characterized small molecules, TEPP-46, inhibited LPS-induced Hif-1α and IL-1β, as well as the expression of a range of other Hif-1α-dependent genes. Activation of PKM2 attenuated an LPS-induced proinflammatory M1 macrophage phenotype while promoting traits typical of an M2 macrophage. LPS-induced PKM2 enters into a complex with Hif-1α, which can directly bind to the IL-1β promoter, an event that is inhibited by activation of PKM2. TEPP-46 inhibited LPS-induced glycolytic reprogramming and succinate production. Finally, activation of PKM2 by TEPP-46 in vivo inhibited LPS and Salmonella typhimurium-induced IL-1β production, while boosting production of IL-10. PKM2 is therefore a critical determinant of macrophage activation by LPS, promoting the inflammatory response.


Kinase Assay: Pyruvate kinase activity is measured by monitoring pyruvate-dependent conversion of NADH to NAD+ by lactate dehydrogenase (LDH) as described previously. Briefly, for cell line experiments, the medium is replaced with fresh medium 1 hour prior to the start of treatment with DMSO or activator. Also, where indicates, 100 μM pervanadate is added 10 minutes prior to cell lysis. Cells are lysed on ice with NP-40 buffer containing 2 mM DTT and protease inhibitors and clarified by centrifugation at 21,000 x g. 5 μL of the supernatant is used to assess pyruvate kinase activity. Pyruvate kinase activity is subsequently normalized for total protein content.


Cell Assay: 2,000 cells are seeded in 96-well plates 24 h prior to treatment start. CellTiter96(R) 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).

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
Animal model Mice
Formulation & Dosage 150 mg/kg
References Nat Chem Biol. 2012 Oct;8(10):839-47.