Brigimadlin
Brigimadlin is a tablet that frees the p53 'guardian' protein from MDM2, the protein that liposarcomas make in excess to keep p53 switched off. It is being compared with doxorubicin as first treatment for dedifferentiated liposarcoma in a phase 2/3 trial.
Overview
Brigimadlin (BI 907828) is Boehringer Ingelheim's oral MDM2-p53 antagonist, dosed once every three weeks to limit the thrombocytopenia that troubled earlier MDM2 inhibitors. Dedifferentiated liposarcoma almost always carries MDM2 amplification with wild-type TP53, so it is the model disease for the class. In the phase 1a/1b trial, responses and long disease control were seen in MDM2-amplified liposarcoma.
The Brightline-1 phase 2/3 trial compares brigimadlin with doxorubicin as first-line treatment for advanced dedifferentiated liposarcoma, and Brightline-2 tests it in other MDM2-amplified, TP53 wild-type cancers such as biliary tract and pancreatic cancer. The liposarcoma page names it with CDK4/6 inhibitors among the targeted drugs in late trials for MDM2-amplified disease.
Binds MDM2 in the pocket that normally holds p53, releasing p53 from degradation; in tumours with MDM2 amplification and intact TP53, such as dedifferentiated liposarcoma, restored p53 stops the cycle and triggers cell death. Connects to MDM2.
1.Brigimadlin slips into a pocket on MDM2.
Trials
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Latest papers
topQuery for this drug: (TITLE:"Brigimadlin" OR ABSTRACT:"Brigimadlin" OR TITLE:"BI 907828" OR ABSTRACT:"BI 907828" OR TITLE:"BI-907828" OR ABSTRACT:"BI-907828") AND (cancer OR tumor OR tumour OR oncology OR carcinoma OR lymphoma OR leukemia OR leukaemia OR myeloma OR sarcoma OR melanoma OR glioma). Results are unfiltered search hits about Brigimadlin, not a curated reading list.
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