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Nexturastat A

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Chemical Structure| 1403783-31-2 同义名 : -
CAS号 : 1403783-31-2
货号 : A293543
分子式 : C19H23N3O3
纯度 : 99%+
分子量 : 341.404
MDL号 : MFCD28099804
存储条件：

粉末 Sealed in dry,Room Temperature

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 55 mg/mL(161.1 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
靶点

  • HDAC6

    HDAC6, IC50:5 nM
描述 Histone deacetylases (HDACs) participate in the control of cellular biological processes via specificly removing acetyl groups on lysine residues in histones and non-histone proteins. The isoform of HDAC6 is orientated in the cytoplasm and mainly interacts with non-histone proteins. It plays a central role in microtubule-dependent cell motility via deacetylation of tubulin. In addition to its protein deacetylase activity, HDAC6 plays a key role in the degradation of misfolded proteins. Nexturastat A is a HDAC6 selective inhibitor with IC50 of 5.02nM, while the IC50s of it against HDAC1, 2, 3, 4, 5, 7, 8, 9, 10, 11 were 3.02μM, 6.92μM, 6.68μM, 9.39μM, 11.7μM, 4.46μM, 0.95μM, 6.72μM, 7.57μM and 5.14μM, respectively[3]. Treatment of B16 cells with Nexturastat A at doses ranging from 1nM to 10000nM concentration dependently increased acetyl-tubulin levels[3]. 10μM, 20μM , 30μM and 40μM Nexturastat A dose-dependently impaired the viability of multiple myeloma PRMI-8226 and U266 cell lines. 48h treatment of Nexturastat A at the concentration of 40μM induced apoptosis in RPMI-8226 and U266 cells[4]. In SM1 murine melanoma tumor model established in C57BL/6 mice, Nexturastat A was administrated 5 times a week at the dose of 15mg/kg, or in combination of anti-PD-1 for 25 days. At day25, the tumor volume of the combination group, Nexturastat A group, anti-PD-1 group and control group were 257.3mm3, 750.1 mm3, 1030 mm3 and 2034 mm3, respectively[5].
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

2.93mL

0.59mL

0.29mL

14.65mL

2.93mL

1.46mL

29.29mL

5.86mL

2.93mL
参考文献

[1]Miyake Y, Keusch JJ, et al. Structural insights into HDAC6 tubulin deacetylation and its selective inhibition. Nat Chem Biol. 2016 Sep;12(9):748-54.

[2]Bergman JA, Woan K, et al. Selective histone deacetylase 6 inhibitors bearing substituted urea linkers inhibit melanoma cell growth. J Med Chem. 2012 Nov 26;55(22):9891-9.

[3]Bergman JA, Woan K, Perez-Villarroel P, Villagra A, Sotomayor EM, Kozikowski AP. Selective histone deacetylase 6 inhibitors bearing substituted urea linkers inhibit melanoma cell growth. J Med Chem. 2012 Nov 26;55(22):9891-9.

[4]Sun X, Xie Y, Sun X, Yao Y, Li H, Li Z, Yao R, Xu K. The selective HDAC6 inhibitor Nexturastat A induces apoptosis, overcomes drug resistance and inhibits tumor growth in multiple myeloma. Biosci Rep. 2019 Mar 22;39(3):BSR20181916.

[5]Knox T, Sahakian E, Banik D, Hadley M, Palmer E, Noonepalle S, Kim J, Powers J, Gracia-Hernandez M, Oliveira V, Cheng F, Chen J, Barinka C, Pinilla-Ibarz J, Lee NH, Kozikowski A, Villagra A. Selective HDAC6 inhibitors improve anti-PD-1 immune checkpoint blockade therapy by decreasing the anti-inflammatory phenotype of macrophages and down-regulation of immunosuppressive proteins in tumor cells. Sci Rep. 2019 Apr 16;9(1):6136.