CADD522 是一种RUNX2-DNA结合抑制剂 (下调RUNX2介导的下游靶基因的转录)，其IC50值为 10 nM。CADD522 还可通过增加线粒体驱动的细胞 ROS 水平发挥其抗肿瘤活性。CADD522 能抑制体内原发肿瘤的生长和免疫受损小鼠肺部肿瘤细胞的实验性转移，可用于癌症的研究。
| 生物活性 | CADD522 is aRUNX2-DNAbinding inhibitor (downregulatesRUNX2-mediated transcription of downstream target genes), with anIC50of 10 nM. CADD522 inhibits primary tumor growth and experimental metastasis of tumor cells in the lungs of immune-compromised mice. CADD522 can be used in study ofcancer[1][2]. |
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体外研究
(In Vitro) | CADD522 (0-100 μM; 24-72 h) exhibits a strong inhibitory effect on BC cell growth and survival[1].
CADD522 (50 μM; 72 h) shows anti-proliferative effect by inducing cell cycle arrest (G1 phase)[1].
CADD522 (50 μM; 8 days) inhibits tumorsphere formation and (50 μM; 24 h) in vitro invasion of BC cells (without cellular toxicity)[1].
CADD522 (2, 10, 25, 50, 100 μM; 48 h) inhibits RUNX2 transcriptional activity by inhibiting RUNX2-DNA binding in T47D-RUNX2 and T47D-Empty cells[1].
CADD522 (50 μM; 72 h) upregulates RUNX2 levels through increased RUNX2 stability in cells[1].
CADD522 (50 μM; 6 or 24 h) increases ROS generation of mitochondrial in MCF7 and MDA-468 cells[2].
CADD522 (0-2000 nM, 30 min) inhibits mitochondrial ATP synthase activity in MDA-231 and MDA-468 cells[2].
Cell Viability Assay[1] | Cell Line: | MDA-MB-468, MCF7, MCF10A, IEC-6, GES-1 and C2C12 cells | | Concentration: | 0-100 μM | | Incubation Time: | 24-72 h | | Result: | Displayed a dose- and time-dependent cell growth inhibition over 72 h.
Exhibited low cytotoxicity for normal cell growth. |
Cell Cycle Analysis[1] | Cell Line: | MCF7, MDA-468 and MDA-231 cells | | Concentration: | 50 μM | | Incubation Time: | 72 h | | Result: | Induced MDA-231 cells accumulated at the G1 and G2/M phase whereas MCF7 and MDA-468 cells were at the G1 phase. |
Cell Viability Assay[1] | Cell Line: | MCF7, MCF7-tet-off cells | | Concentration: | 50 μM | | Incubation Time: | 8 days | | Result: | Dramatically decreased the size as well as the number of tumorspheres, and severely disrupted tumorspheres at day 4.
Showed a relatively selective effect on BC cells (did not have a significant influence on mammosphere formation of the MCF10A non-malignant mammary epithelial cells). |
Cell Invasion Assay[1] | Cell Line: | MCF7-tet-off (+Doxy), MCF7-tet-off (-Doxy) cells | | Concentration: | 50 μM | | Incubation Time: | 24 h | | Result: | Almost abrogated the invasiveness of both MCF7-tet-off (+Doxy) and MCF7-tet-off (-Doxy) cells without cellular toxicity. |
Cell Viability Assay[1] | Cell Line: | T47D-RUNX2 and T47D-Empty cells | | Concentration: | 2, 10, 25, 50, 100 μM | | Incubation Time: | 48 h | | Result: | Resulted in a dramatic decrease of the promoter-luciferase (Luc) activities of RUNX2 downstream target genes such as MMP13 and VEGF (metastasis markers) and OC (osteogenesis marker). |
RT-PCR[1] | Cell Line: | T47D and MCF7 cells (ectopic expressing RUNX2) | | Concentration: | 50 μM | | Incubation Time: | 72 h | | Result: | Significantly inhibited the mRNA level (RUNX2-mediated) of Glut-1 and LDHA. |
Western Blot Analysis[1] | Cell Line: | T47D-RUNX2 and MCF7-RUNX2 cells | | Concentration: | 50 μM | | Incubation Time: | 72 h | | Result: | Enhanced both mRNA and protein expression of RUNX2. |
Western Blot Analysis[1] | Cell Line: | MDA-468 and MDA-231 cells | | Concentration: | 50 μM | | Incubation Time: | 2, 4, 6 h | | Result: | Increased RUNX2 stability by delaying protein degradation. |
Cell Viability Assay[2] | Cell Line: | MCF7 and MDA-468 cells | | Concentration: | 50 μM | | Incubation Time: | 6 or 24 h | | Result: | Increased the level of mitochondrial ROS, which was more evident in serum-free than serum-containing condition. |
Cell Viability Assay[2] | Cell Line: | MDA-231 and MDA-468 cells | | Concentration: | 50, 250, 2000 nM (for MDA-231); 500, 2000 nM (for MDA-468) | | Incubation Time: | 30 min | | Result: | Inhibited the activity of A TP synthase. |
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体内研究
(In Vivo) | CADD522 (1, 5 and 20 mg/kg; i.p.; twice a week for 45 days) delays the onset of the tumors and suppresses tumor growth in mice[1].
CADD522 (10 mg/kg; i.p.; twice a week for 11 days) suppresses tumor metastasis and inhibits expression of Ki-67 in mice[1].
| Animal Model: | Female mice (6-week-old; MMTV-PyMT transgenic model)[1]. | | Dosage: | 1, 5 and 20 mg/kg | | Administration: | Intraperitoneal injection; twice a week for 45 days. | | Result: | Delayed the onset of the tumors, delayed tumor development and reduced tumor burden in transgenic MMTV-PyMT mice.
Reduced the tumor weight in mice. |
| Animal Model: | Female NOD scid gamma (NSG) mice and nude mice (TNBC-PDX Br-001 model)[1]. | | Dosage: | 10 mg/kg | | Administration: | Intraperitoneal injection; twice a week for 11 days. | | Result: | Significant decreased tumor volume and markedly inhibited expression of Ki-67.
Inhibited experimental metastasis of BC cells in vivo.(did not significantly decrease body weight or influence the general health of animals). |
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| 运输条件 | Room temperature in continental US; may vary elsewhere. |
| 储存方式 | 4°C, stored under nitrogen *In solvent : -80°C, 6 months; -20°C, 1 month (stored under nitrogen) |
| 溶解性数据 | In Vitro: DMSO : 250 mg/mL(766.47 mM;Need ultrasonic) 配制储备液 | 1 mM | 3.0659 mL | 15.3294 mL | 30.6589 mL | | 5 mM | 0.6132 mL | 3.0659 mL | 6.1318 mL | | 10 mM | 0.3066 mL | 1.5329 mL | 3.0659 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 (stored under nitrogen)。-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: ≥ 2.17 mg/mL (6.65 mM); Clear solution
此方案可获得 ≥ 2.17 mg/mL (6.65 mM，饱和度未知) 的澄清溶液。 以 1 mL 工作液为例，取 100 μL 21.7 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%corn oil Solubility: ≥ 2.17 mg/mL (6.65 mM); Clear solution
此方案可获得 ≥ 2.17 mg/mL (6.65 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 21.7 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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