For research use only. Not for therapeutic Use.
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 h) inhibits viability and induces cell death in brain tumor stem cells (BTSCs)[3].
Brigimadlin (1-50 nM, 48 h) induces apoptosis and increases p53 transcriptional targets (p21 and PUMA) in BT48, BT67, BT73 cells[3].
Brigimadlin (1 nM, 48 h) disrupts the interaction between MDM2 and wild-type p53 in brain tumor stem cells (BTSCs)[3].
Brigimadlin (15 and 50 mg/kg, p.o., once a week) inhibits tumor growth and increases median survival in orthotopic xenografts of both a MDM2 amplified (BT48) and a normal CN (BT67), TP53 wild-type BTSC model[3].
Brigimadlin (50 mg/kg, p.o., a single dose) increasees PD biomarkers (CDKN1a and GDF15) in the brain in orthotopic GBM patient-derived BTSC models (BT48 and BT67) in SCID mice, and has low systemic clearance[3].
| Catalog Number | I041941 |
| CAS Number | 2095116-40-6 |
| Synonyms | (3S,10’S,11’S,14’S)-6-chloro-11′-(3-chloro-2-fluorophenyl)-13′-(cyclopropylmethyl)-6′-methyl-2-oxospiro[1H-indole-3,12′-8,9,13-triazatetracyclo[7.6.0.02,7.010,14]pentadeca-1,3,5,7-tetraene]-5′-carboxylic acid |
| Molecular Formula | C31H25Cl2FN4O3 |
| Purity | ≥95% |
| InChI | InChI=1S/C31H25Cl2FN4O3/c1-14-17(29(39)40)8-9-18-23-12-24-28(38(23)36-27(14)18)25(19-3-2-4-21(33)26(19)34)31(37(24)13-15-5-6-15)20-10-7-16(32)11-22(20)35-30(31)41/h2-4,7-11,15,24-25,28H,5-6,12-13H2,1H3,(H,35,41)(H,39,40)/t24-,25-,28+,31+/m0/s1 |
| InChIKey | AMTXDBGKYPDTTA-SJVQGLCSSA-N |
| SMILES | CC1=C(C=CC2=C3CC4C(N3N=C12)C(C5(N4CC6CC6)C7=C(C=C(C=C7)Cl)NC5=O)C8=C(C(=CC=C8)Cl)F)C(=O)O |
| Reference | [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. [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. |
