666-15 是一种有效的选择性CREB抑制剂，IC50为 81 nM。666-15 抑制乳腺癌异种移植模型中的肿瘤生长。
| 生物活性 | 666-15 is a potent and selectiveCREBinhibitor with anIC50of 81 nM. 666-15 suppresses tumor growth in a breastcancerxenograft model[1][2]. |
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体外研究
(In Vitro) | 666-15 (73 nM; for 12 hours) significantly blocks the effects caused by MSN overexpression, including cell proliferation, invasion, soft agar colony formation ability, and the expression of CREB downstream genes. 666-15 inhibits MSN overexpression-induced CREB phosphorylation[2].
666-15 (1μM; pretreated 2 hour) effectively inhibits PE-induced CREB phosphorylation. 666-15 significantly decreases the protein expression of ANP and β-MHC and inhibits the activation of ER stress, including the expression of GRP78, CHOP, ATF6, and the phosphorylation of IRE1 in PE + siRNA + 666-15 group and PE + si-CTRP3 + 666-15 group[3].
666-15 potently inhibits cancer cell growth. In MDA-MB-231 and MDA-MB-468 cells, the GI50for 666-15 is 73 and 46 nM, respectively. In A549 and MCF-7 cells, it exhibits robust activity as well with GI50of 0.47 and 0.31 μM. 666-15 is also found to be a rather weak inhibitor of CREB-CBP interaction with IC50of 18.27 μM. 666-15 inhibits CREB’s transcription activity in living cells independent of direct CREB or CBP binding interaction. 666-15 is very potent in inhibiting CREB’s transcription activity. 666-15 also inhibits endogenous CREB target gene expression, the transcript level of nuclear receptor related 1 protein (Nurr1/NR4A2)[1].
Cell Proliferation Assay[2] | Cell Line: | CTRL or MSN-overexpressing MDA-MB-231 cells | | Concentration: | 73 nM | | Incubation Time: | For 12hours | | Result: | Significantly blocked the cell proliferation caused by MSN overexpression. |
Western Blot Analysis[3] | Cell Line: | NRCMs | | Concentration: | 1 μM | | Incubation Time: | 2 hour (pretreated) | | Result: | Effectively inhibited PE-induced CREB phosphorylation. |
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体内研究
(In Vivo) | 666-15 (10 mg/kg; IP; once a week; for 11 weeks) alone can play a good role in inhibiting the growth of breast cancer, and the combination with RP-56976 (DOC) shows a better effect[2].
| Animal Model: | 1-month-old female nude mice with MDA-MB-231 or T47D cells[2] | | Dosage: | 10 mg/kg | | Administration: | IP; once a week; for 11 weeks | | Result: | Played a good role in inhibiting the growth of breast cancer. |
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| 运输条件 | Room temperature in continental US; may vary elsewhere. |
| 储存方式 | 4°C, sealed storage, away from moisture *In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture) |
| 溶解性数据 | In Vitro: DMSO : 125 mg/mL(201.44 mM;ultrasonic and warming and heat to 60℃) 配制储备液 | 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 |
*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℃, 6 months; -20℃, 1 month (sealed storage, away from moisture)。-80℃ 储存时，请在 6 个月内使用，-20℃ 储存时，请在 1 个月内使用。 In Vivo: 请根据您的实验动物和给药方式选择适当的溶解方案。以下溶解方案都请先按照In Vitro方式配制澄清的储备液，再依次添加助溶剂： ——为保证实验结果的可靠性，澄清的储备液可以根据储存条件，适当保存；体内实验的工作液，建议您现用现配，当天使用；
以下溶剂前显示的百
分比是指该溶剂在您配制终溶液中的体积占比；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的方式助溶 1. 请依序添加每种溶剂： 10% DMSO 40%PEG300 5%Tween-80 45% saline Solubility: ≥ 2.08 mg/mL (3.35 mM); Clear solution
此方案可获得 ≥ 2.08 mg/mL (3.35 mM，饱和度未知) 的澄清溶液。 以 1 mL 工作液为例，取 100 μL 20.8 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀；向上述体系中加入50 μL Tween-80，混合均匀；然后继续加入 450 μL生理盐水定容至 1 mL。 2. 请依序添加每种溶剂： 10% DMSO 90% (20%SBE-β-CDin saline) Solubility: 2.08 mg/mL (3.35 mM); Suspended solution; Need ultrasonic
此方案可获得 2.08 mg/mL (3.35 mM) 的均匀悬浊液，悬浊液可用于口服和腹腔注射。 以 1 mL 工作液为例，取 100 μL 20.8 mg/mL 的澄清 DMSO 储备液加到 900 μL20% 的 SBE-β-CD 生理盐水水溶液中，混合均匀。 3. 请依序添加每种溶剂： 10% DMSO 90%corn oil Solubility: ≥ 2.08 mg/mL (3.35 mM); Clear solution
此方案可获得 ≥ 2.08 mg/mL (3.35 mM，饱和度未知) 的澄清溶液，此方案不适用于实验周期在半个月以上的实验。 以 1 mL 工作液为例，取 100 μL 20.8 mg/mL 的澄清 DMSO 储备液加到 900 μL玉米油中，混合均匀。 *以上所有助溶剂都可在本网站选购。
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