ARV-771
目录号 : GC32685
ARV-771是一种泛BET-PROTAC，能有效降解BRD2/3/4蛋白，DC50值低于5nM。
Cas No.:1949837-12-0
Sample solution is provided at 25 µL, 10mM.
_1-3.$$$39978408@51.jpg');)
_1-9.$$$38538795@65.jpg');)
_1-9.$$$39112701@51.jpg');)
_1-7.$$$37316672@70.jpg');)
_366-372.$$$36198801@70.jpg');)
.$$$38565142@65.jpg');)
_1867-1883.$$$33248023@67.jpg');)
_eads6055.$$$39977546@45.jpg');)
_eadm9805.$$$40080571@45.jpg');)
_eadj3020.$$$39666821@45.jpg');)
_1-20.$$$39757301@28.jpg');)
_1-24.$$$38898113@28.jpg');)
_273-287.$$$36806353@46.jpg');)
_1-16.$$$37156877@44.jpg');)
_1-19.$$$37460805@44.jpg');)
_1291-1307.$$$34518654@46.jpg');)
ARV-771, a pan-BET-PROTAC, potently degrades BRD2/3/4 with a DC50<5nM[1]. ARV-771, which consists of a BRD4 inhibitor (JQ1) and a ligand for Von Hippel-Lindau (VHL) E3 ligase, kills cancer cells by degrading bromodomain and BET proteins overexpressed in cancer cells [2]. ARV-771 has been widely used to inhibit tumor growth in MYC/ BCL2-associated lymphoma models[3].
In vitro, ARV-771 treatment for 96 hours significantly inhibited the viability of MDA-MB-231 and MDA-MB-436 cells with IC50 values of 0.12±0.04µM and 0.45±0.02µM, respectively[4]. Treatment of HepG2 and HCCLM3 cells with 2µM ARV-771 for 24 hours significantly inhibited cell growth, blocked cell cycle progression, and reduced the expression of multiple deubiquitinating enzymes[5]. ARV-771 treatment for 48h significantly induced apoptosis in Mino cells with an IC50 value of 17±7nM[6].
In vivo, ARV-771 treatment via subcutaneous administration daily at a dose of 30mg/kg for 21 days induced tumor regression in noncastrated male Nu/Nu mice bearing 22Rv1 tumors[7]. Treatment with ARV-771 (30mg/kg subcutaneously once daily for 5 days per week) combined with BC2059 (30mg/kg intraperitoneally twice weekly) for 3 weeks significantly reduced secondary acute myelocytic leukemia (AML) tumor burden and improved survival in NSG mice bearing HEL-P/R cells[8].
References:
[1] Yedla P, Babalghith A O, Andra V V, et al. PROTACs in the management of prostate cancer[J]. Molecules, 2023, 28(9): 3698.
[2] Cho H, Jeon S I, Shim M K, et al. In situ albumin-binding and esterase-specifically cleaved BRD4-degrading PROTAC for targeted cancer therapy[J]. Biomaterials, 2023, 295: 122038.
[3] Furukawa K, Shimada K, Esaki M, et al. Development and efficacy of a Novel Bromodomain and Extraterminal Domain Degrader K-256 in MYC/BCL2-Related lymphoma[J]. Blood, 2023, 142: 5008.
[4] Teufelsbauer M, Stickler S, Eggerstorfer M T, et al. BET-directed PROTACs in triple negative breast cancer cell lines MDA-MB-231 and MDA-MB-436[J]. Breast Cancer Research and Treatment, 2024, 208(1): 89-101.
[5] Deng Y, Yu C, Chen L, et al. ARV-771 acts as an inducer of cell cycle arrest and apoptosis to suppress hepatocellular carcinoma progression[J]. Frontiers in Pharmacology, 2022, 13: 858901.
[6] Sun B, Fiskus W, Qian Y, et al. BET protein proteolysis targeting chimera (PROTAC) exerts potent lethal activity against mantle cell lymphoma cells[J]. Leukemia, 2018, 32(2): 343-352.
[7] Raina K, Lu J, Qian Y, et al. PROTAC-induced BET protein degradation as a therapy for castration-resistant prostate cancer[J]. Proceedings of the National Academy of Sciences, 2016, 113(26): 7124-7129.
[8] Saenz D T, Fiskus W C, Manshouri T, et al. BRD4 degrader and inhibitor of beta catenin-TCF7L2 are synergistically active against human AML cells resistant to BET inhibitor[J]. Cancer Research, 2019, 79(13_Supplement): 3036-3036.
ARV-771是一种泛BET-PROTAC，能有效降解BRD2/3/4蛋白，DC50值低于5nM[1]。ARV-771由BRD4抑制剂和VHL E3连接酶配体构成，通过降解癌细胞中过表达的溴结构域和BET蛋白发挥抗肿瘤作用[2]。ARV-771已广泛应用于MYC/BCL2相关淋巴瘤模型的肿瘤生长抑制研究[3]。
在体外，ARV-771处理96小时可显著抑制MDA-MB-231和MDA-MB-436细胞活力，IC50值分别为0.12±0.04µM和0.45±0.02µM [4]。使用2µM的ARV-771处理HepG2和HCCLM3细胞24小时，能显著抑制细胞生长、阻滞细胞周期进程并降低多种去泛素化酶表达[5]。ARV-771处理48小时可显著诱导Mino细胞凋亡，IC50值为17±7nM[6]。
在体内，每日皮下注射30mg/kg剂量的ARV-771连续21天，能引起携带22Rv1肿瘤的非去势雄性Nu/Nu小鼠肿瘤消退[7]。采用ARV-771（30mg/kg；每周5次皮下注射）联合BC2059（30mg/kg；每周两次腹腔注射）治疗3周，可显著减轻携带HEL-P/R细胞的NSG小鼠的继发性急性髓细胞白血病（AML）肿瘤负荷，并提高小鼠生存率[8]。
| Cell experiment [1]: | |
Cell lines | MDA-MB-231 cells |
Preparation Method | MDA-MB-231 cells were cultured in RPMI-1640 medium supplemented with 10% FBS and 1% antibiotics. Culture conditions were 37°C with 5% CO2. 1×104 cells in 100μl of medium were aliquoted into wells of a 96-well flat-bottom microtiter plate, and ARV-771 (0.2, 0.039, 0.078, 0.156, 0.313, 0.625, 1.25, 2.5, and 5µM) was added. The plates were incubated for 96h under tissue culture conditions and supplemented with MTT reagent. Viable cells were detected at 450nm. |
Reaction Conditions | 0.2, 0.039, 0.078, 0.156, 0.313, 0.625, 1.25, 2.5, and 5µM; 96h |
Applications | ARV-771 significantly inhibited the viability of MDA-MB-231 cells in a dose-dependent manner. |
| Animal experiment [2]: | |
Animal models | Nude mice |
Preparation Method | Five to six weeks old nude mice were maintained in a standard sterile environment. First, HepG2 cells were digested, washed, and collected in cold PBS. Then 2×106 cells in 100μl PBS were inoculated subcutaneously into each nude mouse within 30min. Nude mice with successfully transplanted tumors were randomly divided into two groups (8 mice/group) and treated with ARV-771 (20mg/kg/day; s.c.) or control vehicle every other day. After 25 days of ARV-771 treatment, mice were sacrificed by human vertebral dislocation, and CO2 was inhaled. Tumor volume and body weight of mice were measured every 5 days. Immediately after removal of the xenograft tumors from the mice, the tumors were weighed using an electronic balance. |
Dosage form | 20mg/kg/day for 25 days; s.c. |
Applications | ARV-771 treatment remarkably reduced tumor volume and tumor weight in HepG2 xenograft model of mice. |
References: | |
| Cas No. | 1949837-12-0 | SDF | |
| Canonical SMILES | CC(C(C(C1=CC=C(Cl)C=C1)=N[C@@H](CC(NCCOCCCOCC(N[C@@H](C(C)(C)C)C(N(C[C@H](O)C2)[C@@H]2C(N[C@H](C3=CC=C(C(SC=N4)=C4C)C=C3)C)=O)=O)=O)=O)C5=NN=C(C)N65)=C6S7)=C7C | ||
| 分子式 | C49H60ClN9O7S2 | 分子量 | 986.64 |
| 溶解度 | DMSO : ≥ 50 mg/mL (50.68 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。 |
||
| 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 | |||
 |
1 mg | 5 mg | 10 mg |
| 1 mM | 1.0135 mL | 5.0677 mL | 10.1354 mL |
| 5 mM | 202.7 μL | 1.0135 mL | 2.0271 mL |
| 10 mM | 101.4 μL | 506.8 μL | 1.0135 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: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet