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Updated: Feb 20, 2026

Stimulation of Notch Signaling in Mouse Osteoclast Precursors
Published on: February 28, 2017
Development of a peptide-based inducer of protein degradation targeting NOTCH1
Nobumichi Ohoka1, Takashi Misawa2, Masaaki Kurihara2
1Division of Molecular Target and Gene Therapy Product, National Institute of Health Sciences, 1-18-1, Kamiyoga, Setagaya, Tokyo 158-8501, Japan.
Abstract:
We previously developed a protein knockdown system by small-molecule hybrid compounds named SNIPERs (Specific and Nongenetic IAP-dependent Protein Erasers). Here we report a peptide-based protein knockdown system for inducing degradation of a transcriptional factor NOTCH1. The molecules designed were composed of two biologically active scaffolds: a peptide that binds to the surface of the target protein NOTCH1 and a small-molecule MV1 that binds to the E3 ubiquitin ligase inhibitor of apoptosis protein (IAP), which are expected to cross-link these proteins in cells. Hybrid molecules specifically induced the degradation of the NOTCH1 protein by the proteasome. This system could be a useful method to develop various degradation inducers against a large number of proteins to which small-molecule ligands have not been found.
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