666-15
(Synonyms: Compound 3i) 目录号 : GC32689
666-15是一种选择性环磷酸腺苷反应元件结合蛋白（CREB）抑制剂，IC50值为0.081±0.04μM。
Cas No.:1433286-70-4
Sample solution is provided at 25 µL, 10mM.
666-15 is a selective cyclic AMP response element binding protein (CREB) inhibitor with an IC50 value of 0.081±0.04μM[1]. 666-15 also inhibits the expression of endogenous CREB target genes, namely the transcription level of nuclear receptor-related protein 1 (Nurr1/NR4A2)[1]. CREB is a nuclear transcription factor that can be activated by a variety of extracellular signals (including growth factors and hormones)[2]. 666-15 blocks the neuroprotective effect of necrotizing inhibitor necrotizing inhibitor necrotizing inhibitor 1 (nec-1), which is a specific and effective inhibitor of necroptosis[3].
In vitro, treatment of newborn rat cardiomyocytes (NRCMs) with 666-15 (1µM) for 2h effectively inhibited phenylephrine-induced CREB phosphorylation, but had no significant effect on p38 phosphorylation[4]. Treatment of aged guinea pig chondrocytes with 666-15 (0-500nM) significantly reduced the protein level of p-CREB1 and increased cell viability[5]. 666-15 (0-10µM) treatment of HEK293T cells transfected with different transcription factors for 5-7h showed little or no inhibition of Gal4-MLL, Gal4-c-Myb, Gal4-TEAD4/YAP1, and serum response factor (SRF)-mediated gene transcription[6].
In vivo, 666-15 (10mg/kg) was intraperitoneally injected into mice transplanted with triple-negative breast cancer (TNBC) cells and inhibited breast cancer growth. Combination with docetaxel (DOC) showed better effects and had no significant effect on mouse body weight[7].
References:
[1] Xie F, Li B X, Kassenbrock A, et al. Identification of a potent inhibitor of CREB-mediated gene transcription with efficacious in vivo anticancer activity[J]. Journal of medicinal chemistry, 2015, 58(12): 5075-5087.
[2] Shaywitz A J, Greenberg M E. CREB: a stimulus-induced transcription factor activated by a diverse array of extracellular signals[J]. Annual review of biochemistry, 1999, 68(1): 821-861.
[3] Yang C, Li T, Xue H, et al. Inhibition of necroptosis rescues SAH-induced synaptic impairments in hippocampus via CREB-BDNF pathway[J]. Frontiers in neuroscience, 2019, 12: 990.
[4] Zhang B, Zhang P, Tan Y, et al. C1q-TNF-related protein-3 attenuates pressure overload-induced cardiac hypertrophy by suppressing the p38/CREB pathway and p38-induced ER stress[J]. Cell death & disease, 2019, 10(7): 520.
[5] Wang Y, Wu Z, Yan G, et al. The CREB1 inhibitor 666-15 maintains cartilage homeostasis and mitigates osteoarthritis progression[J]. Bone & Joint Research, 2024, 13(1): 4-18.
[6] Li B X, Gardner R, Xue C, et al. Systemic inhibition of CREB is well-tolerated in vivo[J]. Scientific Reports, 2016, 6(1): 34513.
[7] Qin Y, Chen W, Jiang G, et al. Interfering MSN-NONO complex-activated CREB signaling serves as a therapeutic strategy for triple-negative breast cancer. Sci Adv 6: eaaw9960[J]. 2020.
666-15是一种选择性环磷酸腺苷反应元件结合蛋白（CREB）抑制剂，IC50值为0.081±0.04μM[1]。666-15还抑制内源性CREB靶基因表达，即核受体相关蛋白1（Nurr1/NR4A2）的转录水平[1]。CREB是一种核转录因子，可被多种细胞外信号（包括生长因子和激素）激活[2]。666-15会阻碍坏死抑制素-1（nec-1）的神经保护作用，nec-1是一种特异性、有效的坏死性凋亡抑制剂[3]。
在体外，666-15（1µM）处理新生大鼠心肌细胞（NRCMS）2h，有效抑制了苯肾上腺素诱导的CREB磷酸化，但是对p38磷酸化没有显著影响[4]。666-15（0-500nM）处理老年豚鼠软骨细胞，显著降低了p-CREB1的蛋白水平，提高了细胞活力[5]。666-15（0-10µM）处理用不同转录因子转染的HEK293T 细胞5-7h，对Gal4-MLL、Gal4-c-Myb、Gal4-TEAD4/YAP1、和血清反应因子（SRF）介导的基因转录表现出很少或没有抑制[6]。
在体内，666-15（10mg/kg）通过腹腔注射治疗移植了三阴性乳腺癌（TNBC）细胞的小鼠，抑制了乳腺癌的生长，与多西他赛（DOC）联合使用显示出更好的效果，且对小鼠体重没有明显影响[7]。
| Cell experiment [1]: | |
Cell lines | Neonatal rat cardiac myocytes (NRCMS) |
Preparation Method | NRCMs were incubated with phenylephrine (PE) (50μM) for 24h to induce cardiomyocyte hypertrophy. Before PE treatment, NRCMs were pretreated with 1μM SB 203580 or 1μM 666-15 for 2h to inhibit the phosphorylation of p38 or CREB57. |
Reaction Conditions | 1µM; 2h |
Applications | 666-15 effectively inhibited CREB phosphorylation. However, 666-15 had no significant effect on PE-induced p38 activation. |
| Animal experiment [2]: | |
Animal models | Nude mice |
Preparation Method | One hundred thousand triple-negative breast cancer (TNBC) cells were implanted into the fourth mammary fat pad on both sides of nude mice. After tumors were formed, the mice were divided into four groups and intraperitoneally injected with Vehicle, docetaxel (DOC) (10mg/kg), 666-15 (10mg/kg), or both once a week. The tumor size was monitored once a week, and the tumor images were taken after the mice were killed. |
Dosage form | 10mg/kg; i.p. |
Applications | 666-15 alone can effectively inhibit the growth of breast cancer, and combined with DOC shows better effects, and has no significant effect on the body weight of mice. |
References: | |
| Cas No. | 1433286-70-4 | SDF | |
| 别名 | Compound 3i | ||
| Canonical SMILES | O=C(NC1=CC=C(Cl)C=C1O)C2=CC3=CC=CC=C3C=C2OCCNC(C4=C(OCCCN)C=C(C=CC=C5)C5=C4)=O.Cl | ||
| 分子式 | C33H31Cl2N3O5 | 分子量 | 620.52 |
| 溶解度 | DMSO : ≥ 30 mg/mL (48.35 mM) | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 1.6116 mL | 8.0578 mL | 16.1155 mL |
| 5 mM | 0.3223 mL | 1.6116 mL | 3.2231 mL |
| 10 mM | 0.1612 mL | 0.8058 mL | 1.6116 mL |
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| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
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| % DMSO % % Tween 80 % saline | ||||||||||
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工作液浓度： mg/ml；
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2.
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Quality Control & SDS
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- Purity: >99.50%
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