BETd-260 (ZBC 260)
(Synonyms: ZBC 260) 目录号 : GC32791
BETd-260 (ZBC 260)是一种基于蛋白水解靶向嵌合体（PROTAC）技术设计的异双功能小分子化合物，通过连接Cereblon配体和BET配体来发挥作用。
Cas No.:2093388-62-4
Sample solution is provided at 25 µL, 10mM.
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BETd-260 (ZBC 260) is a heterobifunctional small molecule compound designed based on proteolysis-targeting chimera (PROTAC) technology, acting by linking a Cereblon ligand and a BET ligand[1, 2]. BETd-260 effectively induces the degradation of bromodomain and extraterminal domain (BET) family proteins such as BRD2, BRD3, and BRD4, significantly inhibiting tumor cell proliferation and inducing apoptosis[3, 4].
In vitro, treatment of hepatocellular carcinoma cell lines (HepG2 and BEL-7402 cells) with BETd-260 (10, 30, 100nM) for 48h significantly induced apoptosis in both cell lines, inhibited the expression of anti-apoptotic genes Mcl-1, Bcl-2, and c-Myc, increased the expression of the pro-apoptotic gene Bad, and disrupted mitochondrial membrane integrity[5]. Treatment of osteosarcoma cell lines (MNNG/HOS and Saos-2 cells) with BETd-260 (3nM) for 24h completely depleted BRD3 and BRD4 in MNNG/HOS and Saos-2 cells and significantly inhibited the expression level of BRD2 protein[6].
In vivo, BETd-260 (5mg/kg) administered intravenously to hepatocellular carcinoma (HCC) xenograft mice significantly inhibited the growth of xenograft tumors and induced apoptosis in tumor tissue cells[5].
References:
[1] Fuchs O, Bokorova R. Rationale of targeting protein cereblon as a potential strategy for cancer treatment[J]. Drugs of the Future, 2020, 45(5): 305-317.
[2] Yang C Y, Qin C, Bai L, et al. Small-molecule PROTAC degraders of the Bromodomain and Extra Terminal (BET) proteins—A review[J]. Drug Discovery Today: Technologies, 2019, 31: 43-51.
[3] Cai M, Dong J, Li H, et al. Recent developments in targeting bromodomain and extra terminal domain proteins for cancer therapeutics[J]. Current Medicinal Chemistry, 2022, 29(25): 4391-4409.
[4] Bai L, Zhou B, Yang C Y, et al. Targeted degradation of BET proteins in triple-negative breast cancer[J]. Cancer research, 2017, 77(9): 2476-2487.
[5] Zhang H, Li G, Zhang Y, et al. Targeting BET proteins with a PROTAC molecule elicits potent anticancer activity in HCC cells[J]. Frontiers in oncology, 2020, 9: 1471.
[6] Shi C, Zhang H, Wang P, et al. PROTAC induced-BET protein degradation exhibits potent anti-osteosarcoma activity by triggering apoptosis[J]. Cell death & disease, 2019, 10(11): 815.
BETd-260 (ZBC 260)是一种基于蛋白水解靶向嵌合体（PROTAC）技术设计的异双功能小分子化合物，通过连接Cereblon配体和BET配体来发挥作用[1, 2]。BETd-260 (ZBC 260)能够有效诱导BRD2、BRD3和BRD4等溴化结构域和超终端结构域（BET）家族蛋白的降解，显著抑制肿瘤细胞增殖与诱导细胞凋亡[3, 4]。
在体外，BETd-260（10, 30, 100nM）处理肝癌细胞系（HepG2、BEL-7402细胞）48h，显著诱导了两种细胞凋亡，抑制了抗凋亡基因Mcl-1、Bcl-2、c-Myc的表达，增加了促凋亡基因Bad的表达，破坏了线粒体膜完整性[5]。BETd-260（3nM）处理骨肉瘤细胞系（MNNG/HOS和Saos-2细胞）24h，完全耗竭了MNNG/HOS和Saos-2细胞中的BRD3和BRD4，并显著抑制了BRD2蛋白的表达水平[6]。
在体内，BETd-260（5mg/kg）通过静脉注射治疗肝细胞癌（HCC）异种移植小鼠，显著抑制了小鼠体内异种移植肿瘤的生长，诱导了肿瘤组织细胞凋亡[5]。
| Cell experiment [1]: | |
Cell lines | HepG2、BEL-7402 cells |
Preparation Method | Cells were treated with BETd-260 at concentrations of 10, 30, and 100nM for 48h. Apoptosis was detected by propidium iodide (PI)/annexin V staining combined with flow cytometry. |
Reaction Conditions | 10, 30, 100nM; 48h |
Applications | BETd-260 at 10nM effectively triggered apoptosis in the both HCC cell lines and at 100nM induced 86 and 77% cells apoptosis, respectively, in HepG2 and BEL-7402 cell lines. |
| Animal experiment [1]: | |
Animal models | Balb/c mice |
Preparation Method | HCC cells (5 million cells per tumor) suspended in 0.1mL of Matrigel were injected subcutaneously into the flanks of 6-week-old Balb/c mice to establish subcutaneous tumors. When tumor grafts had reached an average volume of 100mm3, mice were randomized into treated or control groups, with eight mice in each group. BETd-260 (5mg/kg) or vehicle control (10% PEG400: 3% Cremophor: 87% PBS, 2% TPGS: 98% PEG200) was dosed intravenously (i.v.). Tumor volume and animal weights were monitored 1-3 times every week. When tumors reached the size of 200mm3, mice treated with a single dose of BETd-260 or vehicle control were euthanized at 24h time points, and tumor tissues were harvested from animals and post-fixed in 4% paraformaldehyde and or in liquid nitrogen. |
Dosage form | 5mg/kg; i.v. |
Applications | BETd-260 triggered apoptosis in HCC xenograft tissue and profoundly inhibited the growth of HCC xenograft tumors in mice. |
References: | |
| Cas No. | 2093388-62-4 | SDF | |
| 别名 | ZBC 260 | ||
| Canonical SMILES | CCN1N=C(C2CC2)C=C1NC3=NC(C(NCCCCCC4=CC=CC5=C4CN(C6C(NC(CC6)=O)=O)C5=O)=O)=NC7=C3C8=CC(OC)=C(C9=C(C)ON=C9C)C=C8N7 | ||
| 分子式 | C43H46N10O6 | 分子量 | 798.89 |
| 溶解度 | DMSO : 25 mg/mL (31.29 mM);Water : < 0.1 mg/mL (insoluble) | 储存条件 | -80°C, protect from light, stored under nitrogen |
| 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 | 1.2517 mL | 6.2587 mL | 12.5174 mL |
| 5 mM | 250.3 μL | 1.2517 mL | 2.5035 mL |
| 10 mM | 125.2 μL | 625.9 μL | 1.2517 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。
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Quality Control & SDS
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- Purity: >98.00%
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