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DASA-58

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Chemical Structure| 1203494-49-8 同义名 : ML-203;NCGC00185916
CAS号 : 1203494-49-8
货号 : A284203
分子式 : C19H23N3O6S2
纯度 : 99%+
分子量 : 453.532
MDL号 : MFCD29472280
存储条件：

粉末 Keep in dark place,Inert atmosphere,Room temperature

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 35 mg/mL(77.17 mM)，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO
动物实验配方：
生物活性
描述 Pyruvate kinase M2 (PKM2) interacts with phosphotyrosine-containing proteins to regulate glucose metabolism in cells. DASA-58 is a potent activator of recombinant PKM2 with an AC90 value of 680 nM and an AC50 value of 38 nM. In A549-PKM2/kd cell lysates, treatment with 40 μM DASA-58 for 3 hours caused 248% increase of pyruvate kinase activity. Incubation of A549 cells with 0 – 100 μM DASA-58 dose-dependently activated PKM2 with an EC50 value of 19.6 μM. Also in A549 cells, pretreatment with 1 μM DASA-58 prevented pervanadate-induced PKM2 activity inhibition. DASA-58 at 50 μM decreased lactate production in H1299 cells compared to DMSO-treated group. In H1299 cells incubated with [6-14C]-glucose, DASA-58 at 30 μM led to a significant reduction of glucose-derived carbon incorporation into lipids. A549 cells treated with 100 μM DASA-58 showed diminished incorporation of glucose carbons into acetyl-CoA and decreased de novo lipogenesis[3]. Injection of SCID mice with DASA-58-treated PC3 cells (40 μM, 48h incubation) significantly downregulated CAFs-induced lung metastases formation[4].
作用机制 DASA-58 increases PKM2 activity by an allosteric mechanism similar to fructose-1,6-bisphosphate, a glycolytic metabolite fructose that binds to PKM2, inducing a conformational conversion of the enzyme into its most active form[3].
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

2.20mL

0.44mL

0.22mL

11.02mL

2.20mL

1.10mL

22.05mL

4.41mL

2.20mL
参考文献

[1]Palsson-McDermott EM, Curtis AM, 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.

[2]Giannoni E, Taddei ML, et al. Targeting stromal-induced pyruvate kinase M2 nuclear translocation impairs oxphos and prostate cancer metastatic spread. Oncotarget. 2015 Sep 15;6(27):24061-74.

[3]Anastasiou D, Yu Y, Israelsen WJ, Jiang JK, Boxer MB, Hong BS, Tempel W, Dimov S, Shen M, Jha A, Yang H, Mattaini KR, Metallo CM, Fiske BP, Courtney KD, Malstrom S, Khan TM, Kung C, Skoumbourdis AP, Veith H, Southall N, Walsh MJ, Brimacombe KR, Leister W, Lunt SY, Johnson ZR, Yen KE, Kunii K, Davidson SM, Christofk HR, Austin CP, Inglese J, Harris MH, Asara JM, Stephanopoulos G, Salituro FG, Jin S, Dang L, Auld DS, Park HW, Cantley LC, Thomas CJ, Vander Heiden MG. Pyruvate kinase M2 activators promote tetramer formation and suppress tumorigenesis. Nat Chem Biol. 2012 Oct;8(10):839-47.

[4]Giannoni E, Taddei ML, Morandi A, Comito G, Calvani M, Bianchini F, Richichi B, Raugei G, Wong N, Tang D, Chiarugi P. Targeting stromal-induced pyruvate kinase M2 nuclear translocation impairs oxphos and prostate cancer metastatic spread. Oncotarget. 2015 Sep 15;6(27):24061-74.