Brigimadlin  (Synonyms: BI 907828)

Brigimadlin (BI 907828) is an orally active E3 ubiquitin-protein ligase MDM-2 inhibitor, preventing MDM-2 from negatively regulating the tumor suppressor p53. Brigimadlin can be used for antineoplastic research^[1][2][3][4].

Brigimadlin (0-10 nM，48 小时) 可抑制脑肿瘤干细胞 (BTSC) 的活力并诱导细胞死亡^[3]。
Brigimadlin (1-50 nM，48 小时) 可诱导 BT48、BT67、BT73 细胞凋亡并增加 p53 转录靶点 (p21 和 PUMA)^[3]。
Brigimadlin (1 nM，48 小时) 会破坏脑肿瘤干细胞 (BTSC) 中 MDM2 与野生型 p53 之间的相互作用^[3]。

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

Brigimadlin (15 和 50 mg/kg，口服，每周一次) 可抑制 MDM2 扩增 (BT48) 和正常 CN (BT67)、TP53 野生型 BTSC 模型的原位异种移植物的肿瘤生长并增加中位生存期^{[3 ]}。
Brigimadlin (50 mg/kg，口服，单剂量) 可增加原位 GBM 患者衍生的 BTSC 模型 (BT48 和 BT67) SCID 小鼠中大脑中的 PD 生物标志物 (CDKN1a 和 GDF15)，并且具有较低的全身清除率^{[ 3]}。

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

591.46

C₃₁H₂₅Cl₂FN₄O₃

2095116-40-6

固体

White to off-white

Room temperature in continental US; may vary elsewhere.

• [1]. Gollner Andreas, et al. Preparation of spiroindolepyrrolidinone derivatives for use as MDM2-p53 inhibitors: World Intellectual Property Organization, WO2017060431. 2017-04-13.

  [2]. WHO Drug Information-World Health Organization (WHO).

  [3]. Hao X, et al. BI-907828, a novel potent MDM2 inhibitor, inhibits glioblastoma brain tumor stem cells in vitro and prolongs survival in orthotopic xenograft mouse models. Neuro Oncol. 2023 May 4;25(5):913-926.  [Content Brief]

  [4]. Yoo C, et al. Brightline-2: a phase IIa/IIb trial of brigimadlin (BI 907828) in advanced biliary tract cancer, pancreatic ductal adenocarcinoma or other solid tumors. Future Oncol. 2024 Jan 12.  [Content Brief]