| Size | Price | Stock | Qty |
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| 1mg |
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| Other Sizes |
| Targets |
MDM2 (Murine Double Minute 2). Brigimadlin binds to MDM2 with high affinity (IC50 = 2 nM in a cell-free assay). It inhibits the interaction between MDM2 and the transactivation domain of p53, preventing ubiquitination and degradation of p53. It shows selectivity for MDM2 over MDMX (IC50 = 7,944 nM).
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| ln Vitro |
In a cell-free protein-protein interaction assay, Brigimadlin inhibits the p53-MDM2 interaction with an IC50 of 2 nM, with selectivity for MDM2 over MDMX. In cellular assays (BT48, BT67, and BT73 cells), Brigimadlin promotes apoptosis and enhances the transcription of p53 target genes, including p21 and PUMA. It activates the p53 pathway, leading to cell cycle arrest and the induction of apoptosis in tumor cells.
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| ln Vivo |
In vivo, Brigimadlin is orally active and has demonstrated antitumor activity in metastatic biliary tract cancer (BTC), pancreatic ductal adenocarcinoma (PDAC), lung adenocarcinoma, and bladder cancer models. By inhibiting MDM2 and reactivating p53, it suppresses the growth of p53 wild-type tumors. It is currently under clinical investigation for the treatment of advanced solid tumors.
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| Enzyme Assay |
The potency of Brigimadlin is determined in a cell-free TR-FRET (time-resolved fluorescence resonance energy transfer) assay. A biotinylated p53 peptide is incubated with a GST-tagged MDM2 protein, a europium-labeled anti-GST antibody, and a streptavidin-allophycocyanin donor/acceptor pair. Brigimadlin is added at varying concentrations (0.001-1000 nM). The interaction is measured as a ratio of fluorescence at 665 nm to 620 nm, and an IC50 of 2 nM is calculated from the dose-response curve.
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| Cell Assay |
Cancer cells with wild-type p53 (e.g., HCT116, RKO) are treated with Brigimadlin (0.1-1000 nM) for 24-72 hours. The activation of the p53 pathway is assessed by measuring p53 protein levels (which are stabilized), as well as the levels of its target genes, p21 and PUMA, by Western blot and qPCR. Cell cycle arrest (G1 phase) is analyzed by propidium iodide staining and flow cytometry, and apoptosis is measured by Annexin V/PI staining or by the detection of cleaved caspase-3.
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| Animal Protocol |
Brigimadlin is formulated for oral administration, typically in vehicles such as 0.5% methylcellulose or 10% DMSO/40% PEG300/5% Tween-80/45% saline. It is administered orally once daily to mice bearing subcutaneous tumor xenografts (e.g., HCT116, SJSA-1). Doses are typically 10-100 mg/kg. Tumor volume is measured, and at the end of the study, tumors are harvested for Western blot analysis of p53, p21, and PUMA. Immunohistochemistry for Ki-67 and cleaved caspase-3 is performed to assess proliferation and apoptosis, respectively.
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| ADME/Pharmacokinetics |
Brigimadlin is orally active with good bioavailability. Detailed human PK parameters are being established in clinical trials (Phase I). It is metabolized primarily by CYP3A4. In preclinical species, it has a half-life suitable for once-daily oral administration. The compound has a molecular weight of 591.46 g/mol, a formula of C31H25Cl2FN4O3, and is soluble in DMSO (>100 mg/mL) and ethanol (>100 mg/mL).
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| Toxicity/Toxicokinetics |
Preclinical toxicology studies show that Brigimadlin is generally well-tolerated in animals, with the primary observed toxicities being on-target effects (e.g., myelosuppression and gastrointestinal disturbances) associated with p53 activation in normal proliferative tissues. In clinical trials, common adverse events include nausea, vomiting, fatigue, and diarrhea. Dose-limiting toxicities include thrombocytopenia and neutropenia.
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| References | |
| Additional Infomation |
Brigimadlin is an orally potent murine dual microsome 2 (MDM2) inhibitor with potential antitumor activity. After oral administration, Brigimadlin binds to the MDM2 protein, preventing its binding to the transcriptional activation domain of the tumor suppressor protein p53. By inhibiting the MDM2-p53 interaction, the transcriptional activity of p53 is restored, thereby inducing p53-mediated tumor cell apoptosis. Compared to existing MDM2 inhibitors, the pharmacokinetic properties of BI 907828 allow for more optimized dosage and administration regimens, thereby reducing myelosuppression—a dose-limiting toxicity for this type of inhibitor.
A Phase Ia/Ib clinical trial (NCT05173935) evaluating Brigimadlin in patients with advanced solid tumors, including MDM2-amplified tumors and p53 wild-type cancers, has been completed. A Phase II trial for biliary tract cancer and pancreatic cancer is ongoing. The FDA has granted orphan drug designation for the treatment of pancreatic cancer. Brigimadlin is not yet an FDA-approved drug and is for research use. |
| Molecular Formula |
C31H25CL2FN4O3
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|---|---|
| Molecular Weight |
591.459608793259
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| Exact Mass |
590.128
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| CAS # |
2095116-40-6
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| PubChem CID |
129264140
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| Appearance |
White to off-white solid powder
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| LogP |
3.4
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
41
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| Complexity |
1100
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| Defined Atom Stereocenter Count |
4
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| 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
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| InChi Key |
AMTXDBGKYPDTTA-SJVQGLCSSA-N
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| InChi Code |
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
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| Chemical Name |
(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
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.6907 mL | 8.4537 mL | 16.9073 mL | |
| 5 mM | 0.3381 mL | 1.6907 mL | 3.3815 mL | |
| 10 mM | 0.1691 mL | 0.8454 mL | 1.6907 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
Link: https://clinicaltrials.gov/ct2/show/NCT06619509
Conditions:Solid TumoursLink: https://clinicaltrials.gov/ct2/show/NCT03449381
Conditions:NeoplasmsLink: https://clinicaltrials.gov/ct2/show/NCT05218499
Conditions:Liposarcoma, Dedifferentiated
Title:A Study in Patients With Different Types of Advanced Cancer (Solid Tumors) to Test Different Doses of BI 907828 (Brigimadlin) in Combination With BI 754091 (Ezabenlimab) and BI 754111 or BI 907828 (Brigimadlin) in Combination With BI 754091 (Ezabenlimab)
Status:Completed
updateDate:2026-02-18
Ctid:NCT03964233
Link: https://clinicaltrials.gov/ct2/show/NCT03964233
Conditions:NeoplasmsLink: https://clinicaltrials.gov/ct2/show/NCT05372367
Conditions:Solid TumorsLink: https://clinicaltrials.gov/ct2/show/NCT05512377
Conditions:Pancreatic Neoplasms|Solid Tumors|Biliary Tract Cancer|Lung Neoplasms|Bladder CancerLink: https://clinicaltrials.gov/ct2/show/NCT06058793
Conditions:Liposarcoma, DedifferentiatedLink: https://clinicaltrials.gov/ct2/show/NCT06084689
Conditions:Adult Soft Tissue Sarcoma|Non Small Cell Lung Cancer|Triple Negative Breast Cancer|Colorectal Cancer|Biliary Tract CancerLink: https://clinicaltrials.gov/ct2/show/NCT05376800
Conditions:GlioblastomaLink: https://clinicaltrials.gov/ct2/show/NCT05613036
Conditions:Solid TumorsLink: https://clinicaltrials.gov/ct2/show/NCT06370871
Conditions:Advanced Soft Tissue Sarcoma|Undifferentiated Pleomorphic Sarcoma (UPS)|Myxofibrosarcoma (MFS)Products are for research use only; We do not sell to patients
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