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DRUG:

brontictuzumab (OMP-52M51)

i
Other names: OMP-52M51, anti-Notch 1 monoclonal antibody
Associations
Company:
Mereo Biopharma
Drug class:
Notch inhibitor, Stem cell inhibitor
Associations
11ms
Anti-NOTCH1 therapy with OMP-52 M51 inhibits salivary adenoid cystic carcinoma by depressing epithelial-mesenchymal transition (EMT) process and inducing ferroptosis. (PubMed, Toxicol Appl Pharmacol)
Intriguingly, low-dose OMP-52 M51 strongly facilitated the capacity of ferroptosis inducer erastin to trigger ferroptotic cell death, revealing that OMP-52 M51 could improve the sensitivity of ACC cells to ferroptosis. In vivo, OMP-52 M51 administration suppressed tumor growth and induced ferroptosis in the constructed ACC xenograft mouse model. Collectively, our findings demonstrated that NOTCH1 inhibition by OMP-52 M51 represses the proliferation and epithelial-mesenchymal transition (EMT) in ACCs, and promotes ferroptosis, revealing the potential therapeutical application of OMP-52 M51 in ACC.
Journal
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NOTCH1 (Notch 1) • GPX4 (Glutathione Peroxidase 4) • NICD (NOTCH1 intracellular domain)
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NOTCH1 expression
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erastin • brontictuzumab (OMP-52M51)
over1year
Targeting NOTCH1 in combination with antimetabolite drugs prolongs life span in relapsed pediatric and adult T-acute lymphoblastic leukemia xenografts. (PubMed, Exp Hematol Oncol)
Hence, targeting the NOTCH1 signaling pathway may be an effective option to overcome relapsed and refractory T-ALL.Here, we focused on the therapeutic activity of the NOTCH1-specific monoclonal antibody OMP-52M51 in combination either with drugs used during the induction, consolidation, or maintenance phase in mice xenografts established from pediatric and adult relapsed NOTCH1 mutated T-ALL samples...In agreement, both in vitro and in vivo, the greatest effect on leukemia growth reduction was achieved by anti-NOTCH1 therapy in combination with antimetabolite drugs. This result was further corroborated by the longer life span of mice treated with the anti-NOTCH1 in combination with antimetabolites, indicating a novel Notch-targeted therapeutic approach that could ameliorate pediatric and adult T-ALL patients outcome with relapse disease for whom so far, no other therapeutic options are available.
Journal • Combination therapy
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NOTCH1 (Notch 1) • FBXW7 (F-Box And WD Repeat Domain Containing 7)
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NOTCH1 mutation
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brontictuzumab (OMP-52M51)
over1year
Efficacy of NOTCH inhibitors (Ni) relative to prior systemic therapy or observation in patients (pts) with recurrent/metastatic (R/M) adenoid cystic carcinoma (ACC) (ESMO 2023)
Ni included AL101, a gamma-secretase inhibitor, or OMP-52M51, an antibody targeting N1...The efficacy of Ni compares favorably with efficacy of systemic therapies administered prior to Ni. The limited PFS and high rate of tumor progression on non-target lesions suggests Ni combination therapy may be necessary to address ACC heterogeneity.
Clinical • Metastases
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NOTCH1 (Notch 1)
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AL101 • brontictuzumab (OMP-52M51)
almost4years
A computational guided, functional validation of a novel therapeutic antibody proposes Notch signaling as a clinical relevant and druggable target in glioma. (PubMed, Sci Rep)
We functionally assessed the biological effects of the first-in-human tested blocking antibody against Notch1 receptor (brontictuzumab, BRON) in a collection of glioma stem-like cell (GSC) models and compared its effects to genetic Notch1 inhibition as well as classical pharmacological Notch inhibitor treatment using gamma-secretase inhibitor MRK003. We note that the observed phenotype seems only in part due to Notch1 blockage and the drug candidate leads to activation of off target signals. Further studies addressing a possible emergence of therapy resistance due to WNT activation need to be conducted. We further validated our 3D disease modeling technology to be of benefit for drug development projects.
Clinical • Journal
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IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • NOTCH1 (Notch 1) • HES1 (Hes Family BHLH Transcription Factor 1)
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IDH1 mutation • NOTCH1 expression
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MRK003 • brontictuzumab (OMP-52M51)
over4years
Notch1 signaling in NOTCH1-mutated mantle cell lymphoma depends on Delta-Like ligand 4 and is a potential target for specific antibody therapy. (PubMed, J Exp Clin Cancer Res)
DLL4 effectively stimulates Notch1 signaling in NOTCH1-mutated MCL and is expressed by the microenvironment in MCL lymph nodes. Our results indicate that specific inhibition of the Notch1-ligand-receptor interaction might provide a therapeutic alternative for a subset of MCL patients.
Journal
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NOTCH1 (Notch 1)
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NOTCH1 mutation
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brontictuzumab (OMP-52M51)