Selective targeting of ubiquitin and ubiquitin-like E1-activating enzymes with structurally stabilized peptides

Conformationally stabilized peptides that mimic the E2 helix A domain are developed to inhibit the E1-E2 interaction, addressing resistance issues in existing inhibitors and offering a new approach for treating cancers and other diseases involving pathological cell survival.

JP7727551B2Active Publication Date: 2025-08-21DANA FARBER CANCER INSTITUTE INC
View PDF 8 Cites 0 Cited by

Patent Information

Application Number
JP2021561702
Authority / Receiving Office
JP · JP
Patent Type
Patents
Current Assignee / Owner
Priority Date
2019-04-18
Filing Date
2020-04-17
Publication Date
2025-08-21
Estimated Expiration
2040-04-17

AI Technical Summary

Technical Problem

Existing inhibitors of ubiquitin and ubiquitin-like activating enzymes face resistance due to mutations in the ATP-binding sites of these enzymes, necessitating the development of alternative modes of inhibition to effectively target and inhibit these enzymes for treating hematological malignancies and solid tumors.

Method used

Development of conformationally stabilized alpha-helical peptides that mimic the E2 helix A domain, which competitively inhibit the interaction between ubiquitin-activating enzymes (E1) and ubiquitin conjugating enzymes (E2), thereby inhibiting the E1-E2 interaction and E1-mediated thioester transfer.

Benefits of technology

The stabilized peptides effectively inhibit the E1-E2 interaction in a dose-dependent manner, providing a potential alternative to ATP-competitive inhibitors and overcoming resistance mechanisms in cancer cells.

✦ Generated by Eureka AI based on patent content.

Smart Images

  • Figure 0007727551000054
    Figure 0007727551000054
  • Figure 0007727551000055
    Figure 0007727551000055
  • Figure 0007727551000056
    Figure 0007727551000056
Patent Text Reader

Abstract

The present disclosure features structurally stabilized and / or warhead-bearing structurally stabilized peptide inhibitors for targeting ubiquitin-activating enzyme (E1). Methods of using such structurally stabilized peptides and warhead-bearing structurally stabilized peptides in the treatment of E1-expressing or E1-dependent cancers or diseases are also disclosed. Combination therapies including such structurally stabilized and / or warhead-bearing structurally stabilized peptides for the treatment of E1-expressing or E1-dependent diseases are also provided.
Need to check novelty before this filing date? Find Prior Art

Citation Information

Patent Citations

  • Ubiquitin-binding enzymes

    JP1997508263A

  • Regulation of protein levels in eukaryotes

    JP2002536417A

  • Inhibition of retroviral replication through regulation of host cell ubiquitination

    JP2007513878A

  • Inhibitor of e1 activating enzyme

    JP2009528986A

  • Novel activation and transfer cascades for ubiquitin

    JP2010516254A