Brigimadlin is an orally active MDM2-p53 antagonist. Brigimadlin restores wild-type p53 function by blocking the MDM2-p53 interaction, thereby inducing tumor cell cycle arrest or apoptosis[1-2]. Brigimadlin can be used in research related to MDM2-amplified solid tumors such as biliary tract cancer, pancreatic cancer, and lung cancer[3-4].
In vitro, TP53 wild-type brain tumor stem cells were treated with Brigimadlin (1pM-100nM) for 1-5 days. Brigimadlin was able to significantly reduce cell viability and induce cell death, while restoring p53 tumor suppressor function, including inducing p21 expression and apoptosis[5]. TP53 wild-type EHEB chronic lymphocytic leukemia cells were treated with Brigimadlin (30–100nM) for 24-72 hours. Brigimadlin significantly stabilized the p53 protein, upregulated p21WAF1 expression, induced cleavage of PARP, and activated caspase-3/7[6].
In vivo, Brigimadlin (0.125-2mg/kg) was administered orally once per week to mice bearing MDM2-amplified glioblastoma patient-derived xenografts (PDX). Brigimadlin significantly delayed tumor growth and prolonged survival[7]. Brigimadlin (10mg/kg) was administered as a single intracerebroventricular injection 60 minutes after intracerebral hemorrhage modeling in C57BL/6 mice. Brigimadlin significantly improved neurological deficit scores after intracerebral hemorrhage, reduced levels of MDA, Fe²⁺, and ROS in brain tissue, and decreased cell death and pro-inflammatory factor release[8].
References:
[1] Gupta K, Grimison P. Real-World Experience Using Brigimadlin (MDM2 Inhibitor) in an Australian Sarcoma Specialist Center Compared to Pivotal Clinical Trial Results. Asia Pac J Clin Oncol. 2025 Aug;21(4):447-448.
[2] WHO Drug Information-World Health Organization (WHO).
[3] Gollner A, Rudolph D, Weyer-Czernilofsky U, et al. Discovery and Characterization of Brigimadlin, a Novel and Highly Potent MDM2-p53 Antagonist Suitable for Intermittent Dose Schedules. Mol Cancer Ther. 2024 Dec 3;23(12):1689-1702.
[4] Yamamoto N, Tolcher A, Hafez N, et al. Efficacy and Safety of the MDM2-p53 Antagonist Brigimadlin (BI 907828) in Patients with Advanced Biliary Tract Cancer: A Case Series. Onco Targets Ther. 2024 Mar 29;17:267-280.
[5] Hao X, Bahia RK, Cseh O, 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.
[6] Aptullahoglu E. Brigimadlin (BI-907828) and napabucasin (BBI608) cooperatively trigger apoptosis in chronic lymphocytic leukemia cells by simultaneous iİnhibition of MDM2 and STAT3. Mol Biol Rep. 2025 Jul 17;52(1):731.
[7] Vaubel RA, Zhang W, Karbhari N, et al. Pharmacokinetic-pharmacodynamic-efficacy modeling of the MDM2 inhibitor brigimadlin in glioblastoma patient-derived xenografts. Neurooncol Adv. 2025 Dec 15;8(1):vdaf259.
[8] Yu Y, Liu T, Cai Y, et al. MDM2-GPX4-ferroptosis regulatory axis exerts neurotoxic effects in intracerebral hemorrhage. Neural Regen Res. 2025 Aug 13.