RG7388
(Synonyms: RG 7388; RG-7388; ldasanutlin; Ro 5503781) 目录号 : GC11594
RG7388是一种具有口服活性的MDM2（IC50=6nM）拮抗剂，RG7388通过抑制MDM2-p53相互作用来激活p53通路。
Cas No.:1229705-06-9
Sample solution is provided at 25 µL, 10mM.
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RG7388 is an orally active MDM2 antagonist (IC50=6nM) that activates the p53 pathway by inhibiting the MDM2-p53 interaction[1-2]. RG7388 can induce cell cycle arrest to reduce tumor cell proliferation and is applicable for research related to acute myeloid leukemia and solid tumors[3-4].
In vitro, treatment of TP53 wild-type T-cell acute lymphoblastic leukemia (T-ALL) cell line MOLT-3 with RG7388 (0-90nM) for 24-72 hours, RG7388 induced p53-dependent stabilization and accumulation of p53 protein, upregulated the expression of the pro-apoptotic BH3 domain genes BAX and BBC3 (PUMA), and increased caspase-3/7 activity and apoptosis[5]. Treatment of colorectal cancer (CRC) cell lines HCT116 and RKO with RG7388 (1µM) for 24 hours, RG7388 induced p53 protein accumulation. In combination with the HSP90 inhibitor Ganetespib (50nM), RG7388 synergistically reduced cell viability and confluence, and increased cell death and PARP-1 cleavage[6].
In vivo, oral co-administration of RG7388 (40-75mg/kg) with the ALK inhibitor Lorlatinib (10mg/kg) in ALK-amplified neuroblastoma PDX model (GR-NB4) mice (5 times per week for 2-3 weeks) leads to complete tumor regression. The combination therapy enhances apoptotic effects in vivo by activating the p53-BAX pathway[7]. Oral administration of RG7388 (25mg/kg/day) to tumor-bearing (KCNR or KP-N-YN cells) mice (once daily for 3 weeks), RG7388 significantly inhibits tumor growth as a monotherapy. In combination with the BCL-2 inhibitor Venetoclax (100mg/kg), RG7388 induces complete remission or partial tumor regression and significantly delays tumor recurrence[8].
RG7388是一种具有口服活性的MDM2（IC50=6nM）拮抗剂，RG7388通过抑制MDM2-p53相互作用来激活p53通路[1-2]。RG7388可诱导细胞周期阻滞以减少肿瘤细胞增殖，RG7388可用于急性髓系白血病和实体瘤的相关研究[3-4]。
在体外，RG7388（0-90nM）处理TP53野生型的T细胞急性淋巴细胞白血病（T-ALL）细胞系MOLT-3 24-72小时，RG7388以p53依赖的方式诱导p53蛋白稳定和积累，上调促凋亡BH3域基因BAX和BBC3（PUMA）的表达，并引起caspase-3/7活性增加和细胞凋亡 [5]。RG7388（RG7388，1μM）处理结直肠癌（CRC）细胞系HCT116和RKO 24小时，RG7388可诱导细胞p53蛋白积累，与HSP90抑制剂Ganetespib（50nM）联用可协同降低细胞活力和汇合度，增加细胞死亡和PARP-1切割[6]。
在体内，RG7388（40-75mg/kg）与ALK抑制剂Lorlatinib（10mg/kg）联用口服处理ALK扩增型神经母细胞瘤PDX模型（GR-NB4）小鼠（每周5次，持续2-3周），RG7388可导致肿瘤完全消退，且联合治疗在体内通过激活p53-BAX通路增强凋亡效应[7]。RG7388（25mg/kg/day）口服处理荷瘤（KCNR或KP-N-YN细胞）小鼠（每日一次，持续3周），RG7388单药治疗显著抑制肿瘤生长，但与BCL-2抑制剂Venetoclax（100mg/kg）联用时可诱导完全缓解或部分肿瘤消退，并显著延缓肿瘤复发[8]。
| Cell experiment [1]: | |
Cell lines | MOLT-3 cells (human T-cell acute lymphoblastic leukemia cell line) and patient-derived xenograft (PDX) T-ALL cells |
Preparation Method | MOLT-3 cells were maintained in RPMI-1640 medium supplemented with 10% heat-inactivated fetal bovine serum (FBS) at 37°C, 5% CO₂. Isogenic control and TP53 knockout MOLT-3 cells were treated with RG7388 at concentrations of 30–90nM for 24–72hours. |
Reaction Conditions | 30–90nM; 24-72 hours. |
Applications | RG7388 significantly induced p53 protein stabilization and accumulation in TP53-wildtype MOLT-3 cells, leading to upregulation of pro-apoptotic genes BAX and BBC3 (PUMA) at RNA and protein levels. RG7388 treatment resulted in increased caspase-3/7 activity and apoptosis in a p53-dependent manner. |
| Animal experiment [2]: | |
Animal models | Th-ALKF1174L/MYCN genetically engineered mouse model (GEMM) and patient-derived xenograft (PDX) models (GR-NB4, IC-pPDX-112, HSJD-NB-012) |
Preparation Method | Tumor-bearing mice were treated with RG7388 orally at 40-75mg/kg daily on a 5-days-on/2-days-off schedule for 14-21 days, either alone or in combination with Lorlatinib (10mg/kg). Tumor volume was monitored by MRI or caliper measurements. |
Dosage form | 40-75mg/kg; oral gavage; Daily administration (5 days/week for 2-3 weeks). |
Applications | RG7388 monotherapy showed modest tumor growth inhibition in 3 of 4 PDX models, with complete resistance observed in an ETP-ALL model. However, RG7388 combined with Lorlatinib resulted in complete tumor regression in ALK-amplified GR-NB4 PDX models and significantly delayed tumor regrowth across multiple neuroblastoma models. |
References: | |
| Cas No. | 1229705-06-9 | SDF | |
| 别名 | RG 7388; RG-7388; ldasanutlin; Ro 5503781 | ||
| 化学名 | 4-[[(2R,3S,4R,5S)-3-(3-chloro-2-fluorophenyl)-4-(4-chloro-2-fluorophenyl)-4-cyano-5-(2,2-dimethylpropyl)pyrrolidine-2-carbonyl]amino]-3-methoxybenzoic acid | ||
| Canonical SMILES | CC(C)(C)CC1C(C(C(N1)C(=O)NC2=C(C=C(C=C2)C(=O)O)OC)C3=C(C(=CC=C3)Cl)F)(C#N)C4=C(C=C(C=C4)Cl)F | ||
| 分子式 | C31H29Cl2F2N3O4 | 分子量 | 616.48 |
| 溶解度 | ≥ 30.824 mg/mL in DMSO, ≥ 6.96 mg/mL in EtOH with gentle warming | 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 | 1.6221 mL | 8.1106 mL | 16.2211 mL |
| 5 mM | 324.4 μL | 1.6221 mL | 3.2442 mL |
| 10 mM | 162.2 μL | 811.1 μL | 1.6221 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: >99.50%
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