BRD4/CK2-IN-1 是一种首次高效、口服有效的 BRD4/CK2 (含溴结构域蛋白 4/酪蛋白激酶 2) 双靶点抑制剂。BRD4/CK2-IN-1 对 BRD4 和 CK2 的 IC50 值分别为 180 nM 和 230 nM。BRD4/CK2-IN-1具有很强的抗癌活性，且无明显毒性。BRD4/CK2-IN-1 在三阴性乳腺癌 (TNBC) 中诱导细胞凋亡和自噬相关的细胞死亡。
Cas No.:2756851-99-5
Sample solution is provided at 25 µL, 10mM.
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BRD4/CK2-IN-1 is the first highly effective and oral active dual-target inhibitor of BRD4/CK2 (bromodomain-containing protein 4/casein kinase 2), with IC50s of 180 nM and 230 nM for BRD4 and CK2, respectively. BRD4/CK2-IN-1 has strong anticancer activity without obvious toxicities. BRD4/CK2-IN-1 induces apoptosis and autophagy-associated cell death in triple-negative breast cancer (TNBC)[1]
BRD4/CK2-IN-1 (compound 44e) (0-25 μM; 24 hours) has anti-proliferation effect with IC50s of 2.66 and 3.52 μM in MDA-MB-231 and MDA-MB-468 cells, respectively[1].
BRD4/CK2-IN-1 (0-10 μM; 24 hours) dose-dependently induces apoptosis of MDA-MB-231 and MDA-MB-468 cells[1].
BRD4/CK2-IN-1 (0-10 μM; 24 hours) dose-dependently downregulates Bcl-2 but upregulates Bax and cleaved caspase-3[1].
BRD4/CK2-IN-1 (0-10 μM; 24 hours) significantly downregulates the autophagy substrate p62 and up-regulated beclin-1 and LC3II in MDA-MB-231 and MDA-MB[1].
Cell Viability Assay[1]
| Cell Line: | MDA-MB-231, MDA-MB-468 cells |
| Concentration: | 0, 0.19, 0.39, 0.78, 1.56, 3.13, 6.25, 12.5, 25 μM |
| Incubation Time: | 24 hours |
| Result: | Showed anti-proliferative rates in MDA-MB-231 and MDA-MB-468 cells (IC50 = 2.66 and 3.52 μM, respectively). |
Apoptosis Analysis[1]
| Cell Line: | MDA-MB-231, MDA-MB-468 cells |
| Concentration: | 0, 2.5, 5, 10 μM |
| Incubation Time: | 24 hours |
| Result: | Dose-dependently induced apoptosis of MDA-MB-231 and MDA-MB-468 cells. |
Western Blot Analysis[1]
| Cell Line: | MDA-MB-231, MDA-MB-468 cells |
| Concentration: | 0, 2.5, 5, 10 μM |
| Incubation Time: | 24 hours |
| Result: | Dose-dependently downregulated Bcl-2 but upregulated Bax and cleaved caspase-3. |
| Cell Line: | |
| Concentration: | |
| Incubation Time: | |
| Result: |
BRD4/CK2-IN-1 (25 and 50 mg/kg; intragastric administration; daily for 19 days) inhibits tumor growth in TNBC xenograft models[1].
BRD4/CK2-IN-1 (25 and 50mg/kg; intragastric administration; daily for 19 days) shows weak toxicity measured by body weight loss in the MDA-MB-231 and MDA-MB-468 xenograft models[1].
Preliminary Assessment of Pharmacokinetics (PK) profile of BRD4/CK2-IN-1[1].
| Parameter | iv (1 mg/kg) | po (10 mg/kg) |
| T1/2 (h) | 4.21±0.57 | 5.14±0.71 |
| Cmax (ng/mL) | 237±11 | 206±6 |
| AUC0-t (ng.h/mL) | 579±49 | 2079±130 |
| AUC0-∞ (ng.h/mL) | 588±36 | 2090±146 |
| VZ (L/kg) | 21.1±2.6 | |
| CL ((mL/min)/kg) | 57.4±1.3 | |
| F (%) | 32.5 |
| Animal Model: | Female nude mice (BALB/c, 6-8 weeks, 20-22 g) bearing MDA-MB-231 cells[1] |
| Dosage: | 25 and 50 mg/kg |
| Administration: | Intragastric administration; daily for 19 days |
| Result: | Had the most pronounced tumor growth inhibition (TGI) (63.8%) in the MDA-MB-231 xenograft tumor model at 50 mg/kg. |
| Cas No. | 2756851-99-5 | SDF | Download SDF |
| 分子式 | C29H30ClN5O5 | 分子量 | 564.03 |
| 溶解度 | DMSO : 20 mg/mL (35.46 mM; ultrasonic and warming and adjust pH to 3 with HCl and heat to 60°C) | 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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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 1.773 mL | 8.8648 mL | 17.7296 mL |
| 5 mM | 354.6 μL | 1.773 mL | 3.5459 mL |
| 10 mM | 177.3 μL | 886.5 μL | 1.773 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 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 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Quality Control & SDS
- View current batch:
- Purity: >98.00% Appearance: A solid
- COA (Certificate of Analysis)
- SDS (Safety Data Sheet)
- Datasheet