Matthew A Belmonte

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The hedgehog pathway has been implicated in the tumorigenesis, tumor progression, and metastasis of numerous human cancers. We generated the first fully human hedgehog antibody MEDI-5304 and characterized its antitumor activity and preclinical toxicology. MEDI-5304 bound sonic hedgehog (SHH) and Indian hedgehog (IHH) with low picomolar affinity and(More)
Targeted covalent inhibition of disease-associated proteins has become a powerful methodology in the field of drug discovery, leading to the approval of new therapeutics. Nevertheless, current approaches are often limited owing to their reliance on a cysteine residue to generate the covalent linkage. Here we used aryl boronic acid carbonyl warheads to(More)
Authors’ affiliation: Oncology iMED, AstraZeneca-R&D Boston, Waltham, MA Oncology Research, MedImmune LLC, Gaithersburg, MD Translational Oncology Program, University of Michigan, Ann Arbor, MI; Amgen British Columbia, Burnaby, BC, Canada Lead GenerationResearch, Medimmune LLC, Granta Park, Cambridge, UK Clinical Pharmacology and DMPK, MedImmune LLC,(More)
Mcl-1 is a pro-apoptotic BH3 protein family member similar to Bcl-2 and Bcl-xL. Overexpression of Mcl-1 is often seen in various tumors and allows cancer cells to evade apoptosis. Here we report the discovery and optimization of a series of non-natural peptide Mcl-1 inhibitors. Screening of DNA-encoded libraries resulted in hit compound 1, a 1.5 μM Mcl-1(More)
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