| Identification | Back Directory | [Name]
spiro[3H-indol-3,2'(1'H)-pyrrolo[2',3':4,5]pyrrolo[1,2-b]indazol]-7'-carbonsure, 6-chlor-3'-(3-chlor-2-fluorophenyl)-1'-(cyclopropylmethyl)-1,2,3',3'a,10',10'a-hexahydro-6'-methyl-2-oxo-, (3S,3'S,3a'S,10a'S)- | [CAS]
2095116-40-6 | [Synonyms]
spiro[3H-indol-3,2'(1'H)-pyrrolo[2',3':4,5]pyrrolo[1,2-b]indazol]-7'-carbonsure, 6-chlor-3'-(3-chlor-2-fluorophenyl)-1'-(cyclopropylmethyl)-1,2,3',3'a,10',10'a-hexahydro-6'-methyl-2-oxo-, (3S,3'S,3a'S,10a'S)- | [EINECS(EC#)]
826-645-5 | [Molecular Formula]
C31H25Cl2FN4O3 | [MOL File]
2095116-40-6.mol | [Molecular Weight]
591.46 |
| Chemical Properties | Back Directory | [Boiling point ]
788.0±60.0 °C(Predicted) | [density ]
1.68±0.1 g/cm3(Predicted) | [form ]
Solid | [pka]
3.29±0.40(Predicted) | [color ]
White to off-white | [InChIKey]
AMTXDBGKYPDTTA-XUOXQPGYNA-N | [SMILES]
C(C1CC1)N1[C@@]2([H])CC3=C4C=CC(C(=O)O)=C(C)C4=NN3[C@@]2([H])[C@H](C2C=CC=C(Cl)C=2F)[C@@]21C(NC1=CC(Cl)=CC=C21)=O |&1:5,21,23,32,r| |
| Hazard Information | Back Directory | [Description]
Brigimadlin is an E3 ubiquitin-protein ligase Mdm2 inhibitor with potential as an antineoplastic agent. | [Uses]
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]. | [in vivo]
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].
| [References]
[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. DOI:10.1093/neuonc/noac271
[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. DOI:10.2217/fon-2023-0963 |
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