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666-15

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Chemical Structure| 1433286-70-4 同义名 : Compound 3i
CAS号 : 1433286-70-4
货号 : A723775
分子式 : C33H31Cl2N3O5
纯度 : 99%+
分子量 : 620.522
MDL号 : MFCD30182343
存储条件：

粉末 Inert atmosphere,Room Temperature

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 120 mg/mL(193.39 mM)，配合低频超声，并水浴加热至45℃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
动物实验配方：
生物活性
靶点

  • bromodomain

    CREB, IC50:81 nM
描述 cAMP-response element binding protein (CREB) is a nuclear transcription factor that has been implicated in the pathogenesis and maintenance of various types of human cancers. Identification of small molecule inhibitors of CREB-mediated gene transcription has been pursued as a novel strategy for developing cancer therapeutics[1].666-15 is a potent and selective inhibitor of CREB-mediated gene transcription (IC50 = 0.081 ± 0.04 μM). 666-15 also potently inhibited cancer cell growth without harming normal cells[2].In anin vivo MDA-MB-468 xenograft model, 666-15 completely suppressed the tumor growth without overt toxicity. 666-15 was found to be readily bioavailable to achieve pharmacologically relevant concentrations for CREB inhibition. The mice treated with 666-15 showed no evidence of changes in body weight, complete blood count, blood chemistry profile, cardiac contractility and tissue histologies from liver, kidney, and heart[3].Inhibition of CREB's transcriptional activity with 666-15 dramatically enhanced apoptosis in PC12 cells by downregulating B-cell lymphoma 2 (Bcl-2)[4]. 666-15 compound could effectively reverse the anti-inflammatory effect of CBL in primary mouse microglia cells and anti-ischemic brain injury of cerebrolysin in rats subjected to transient middle cerebral artery occlusion(tMAO)[5].After 666-15 or SR-18292 treatment, such protective effect of PEG-IGF-1 can be attenuated, and the mice suffered from the re-deterioration of behavioral and mitochondrial abnormalities in hippocampus[6].
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

1.61mL

0.32mL

0.16mL

8.06mL

1.61mL

0.81mL

16.12mL

3.22mL

1.61mL
参考文献

[1]Fuchun Xie,et al. Design, synthesis and biological evaluation of regioisomers of 666-15 as inhibitors of CREB-mediated gene transcription. Bioorg Med Chem Lett. 2017 Feb 15;27(4):994-998.

[2]Xie F, et al. Identification of a Potent Inhibitor of CREB-Mediated Gene Transcription with Efficacious in Vivo Anticancer Activity. J Med Chem. 2015 Jun 25;58(12):5075-87.

[3]Li BX, et al. Systemic Inhibition of CREB is Well-tolerated in vivo. Sci Rep. 2016 Oct 3;6:34513.

[4] Ye Zhi,et al. Positive regulation of the CREB phosphorylation via JNK-dependent pathway prevents antimony-induced neuronal apoptosis in PC12 cell and mice brain. Neurotoxicology. 2020 Dec;81:101-108.

[5]Xin Guan,et al. Cerebrolysin Ameliorates Focal Cerebral Ischemia Injury Through Neuroinflammatory Inhibition via CREB/PGC-1α Pathway. Front Pharmacol. 2019 Oct 22;10:1245.

[6]Caixia Yang,et al. Exogenous IGF-1 alleviates depression-like behavior and hippocampal mitochondrial dysfunction in high-fat diet mice. Physiol Behav. 2021 Feb 1;229:113236.