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CAY10585

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Chemical Structure| 934593-90-5 同义名 : -
CAS号 : 934593-90-5
货号 : A121335
分子式 : C26H29NO5
纯度 : 97%
分子量 : 435.512
MDL号 : MFCD09907563
存储条件：

粉末 Inert atmosphere,2-8°C

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 25 mg/mL(57.4 mM)，配合低频超声助溶，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

DMF: 15 mg/mL(34.44 mM)，配合低频超声助溶
动物实验配方：
生物活性
靶点

  • HIF

    HIF, IC50:4.4 μM
描述 The response of mammalian cells to hypoxia is mediated by a family of transcription factors known as HIF (hypoxia-inducible factors). The subunits of HIF, HIF-1α can be degraded rapidly under normoxia. LW6 is a dual inhibitor of HIF-1α and MDH2, which can inhibit activity of HIF-1α with IC50 value of 2.64 ± 0.16 μM (measured by HRE-luciferase activity). LW6 can potently inhibit HIF-1α accumulation by degrading HIF-1α on concentration of 10 μM in HCT116 cells under hypoxia, with no effect on transcription levels during hypoxia. LW6 inhibited the MDH2 activity in a concentration-dependent manner with IC50 value of 6.3 μM, without affecting the MDH2 expression. This HIF-1α inhibitory activity of LW6 may due to the interaction and suppression of MDH2 (malate dehydrogenase 2, a 36 kDa mitochondrial enzyme that catalyzes the malate/NAD+ conversion to oxaloacetate/ NADH during the TCA cycle and functions as a respiratory substrate in the mitochondrial ETC) by LW6[1]. The activity of LW6 against HIF-1α may also due to it promotes proteasomal degradation of HIF-1α via upregulation of VHL. Treatment with LW6 for 13 days, 20 mg/kg, QD, i.p., significantly inhibited HCT116 tumor growth up to 53.6% in a xenograft tumor model compared with the control group[2].
作用机制 The action of LW6 against HIF-1α may due to it can promote proteasomal degradation of HIF-1α via upregulation of VHL, as well as inhibit and bind to MDH2[1][2].
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

2.30mL

0.46mL

0.23mL

11.48mL

2.30mL

1.15mL

22.96mL

4.59mL

2.30mL
参考文献

[1]Lee K, Ban HS, et al. Identification of malate dehydrogenase 2 as a target protein of the HIF-1 inhibitor LW6 using chemical probes. Angew Chem Int Ed Engl. 2013 Sep 23;52(39):10286-9.

[2]Lee K, Kang JE, et al. LW6, a novel HIF-1 inhibitor, promotes proteasomal degradation of HIF-1alpha via upregulation of VHL in a colon cancer cell line. Biochem Pharmacol. 2010 Oct 1;80(7):982-9.