Bi 907828 Mdm2 Inhibitor Probechem Biochemicals Biological activity. brigimadlin (bi 907828) is an orally available inhibitor of murine double minute 2 (mdm2) with potential antineoplastic activity, bi 907828 binds to mdm2 protein and prevents its binding to p53. bi 907828 decreases viability and induces cell death at picomolar concentrations, in both mdm2 amplified and normal copy number. Bi 907828 is an mdm2–p53 antagonist that binds to mdm2 and blocks its interaction with p53, thereby restoring p53 function, leading to cell cycle arrest and apoptosis in tp53 wild type tumor cells. in ongoing phase i studies, bi 907828 has demonstrated initial signs of activity in selected advanced metastatic solid tumors, including btc and pdac.
Brigimadlin Bi 907828 Mdm 2 Inhibitor Medchemexpress 487 background: outcomes remain poor for pts treated with standard of care chemotherapy for advanced biliary tract cancer (btc). hence, there is a clinical need for novel therapeutic strategies. one such emerging strategy is antagonism of mouse double minute 2 (mdm2), which is amplified in 5–8% of cases of btc. brigimadlin (bi 907828) is a mdm2–p53 antagonist that blocks the mdm2–p53. The mdm2–p53 antagonist bi 907828 has shown preclinical antitumor activity in a range of malignancies and is currently being assessed in two phase ia ib dose escalation expansion trials in patients with advanced solid tumors: as monotherapy (nct03449381) and in combination with an anti pd 1 antibody, ezabenlimab (nct03964233). Results: bi 907828 decreases viability and induces cell death at picomolar concentrations in both mdm2 amplified and normal copy number tp53 wild type btsc lines. restoration of p53 activity, including robust p21 expression and apoptosis induction, was observed in tp53 wild type but not in tp53 mutant btscs. shrna mediated knock down of tp53 in. Brigimadlin (bi 907828), a highly potent, orally available mdm2–p53 antagonist, inhibits the interaction between the tumor suppressor p53 and its negative regulator mdm22. this leads to stabilization of p53, followed by target gene induction that may result in cell cycle arrest or apoptosis in tumors with tp53 wt status3.
Bi 907828 Boehringer Ingelheim Results: bi 907828 decreases viability and induces cell death at picomolar concentrations in both mdm2 amplified and normal copy number tp53 wild type btsc lines. restoration of p53 activity, including robust p21 expression and apoptosis induction, was observed in tp53 wild type but not in tp53 mutant btscs. shrna mediated knock down of tp53 in. Brigimadlin (bi 907828), a highly potent, orally available mdm2–p53 antagonist, inhibits the interaction between the tumor suppressor p53 and its negative regulator mdm22. this leads to stabilization of p53, followed by target gene induction that may result in cell cycle arrest or apoptosis in tumors with tp53 wt status3. Mdm2 is an endogenous negative regulator of p53, hence aberrations of the mdm2 gene can result in inappropriate silencing of wild type p53, potentially leading to tumorigenesis. 11 mdm2 amplification has been observed in around 5–8% of btcs, 12, 13 with tp53 mutations being mostly mutually exclusive. 12 prevalence of mdm2 amplification varies. Objectives. • the trials were designed to assess the safety, tolerability, and rp2d of bi 907828, both as a monotherapy and in combination with ezabenlimab (and bi 754111, anti lag 3 antibody, in one patient) in a variety of tp53 wt cancers. lag 3, lymphocyte activation gene 3; rp2d, recommended phase ii dose.
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