IDB-001 is a human ribosomal peptidyl transferase center ( PTC ) inhibitor that induces conformational changes and blocks translational elongation in specific sequence contexts through complementary interactions with Asp/Glu residues in nascent polypeptides. IDB-001 preferentially stalls ribosomes at positions containing acidic peptide motifs, thereby inhibiting cancer cell proliferation, and activates the integrated stress response via eIF2α phosphorylation at high concentrations. In addition, IDB-001 mildly triggers ribotoxic stress responses through phosphorylation of JNK and p38. IDB-001 has been applied to mechanistic studies of triple-negative breast cancer [1].
In Vitro, IDB-001 (10 μM; 60 min) induces translation elongation defects characterized by context-dependent stalling, preferentially targeting nascent polypeptide chains with an acidic residue at the -1 position, and elicits mild ribosome collisions upstream of stalling sites in HCC-1143 triple-negative breast cancer cells[1]. IDB-001 potently and specifically inhibits in vitro translation of reporter gene constructs containing acidic tetrameric sequences, exhibiting a biochemical selectivity window of at least 15-fold across different nascent peptide motifs. Its activity against the FTED motif is 3-fold higher than that of IDB-002, and its activity against the DDEY motif is 6-fold higher than that of IDB-002[1]. IDB-001 (50 μM; 30 min) induces a conformational change in the aspartic acid at position -1 of the nascent peptide chain to form a stable salt bridge, and triggers specific structural rearrangement of ribosomal RNA residues, thereby constricting the peptidyl transferase center and regulating the channel volume in human ribosome-nascent chain complexes containing MYC-derived QEDE peptides[1]. IDB-001 inhibits cancer cell proliferation, with an EC50 ranging from 0.663 μM (in HCC-1143 triple-negative breast cancer cells) to 5.440 μM (in MRC-5 fibroblasts). It exhibits the strongest activity against HCC-1143 cells among human cancer cell lines and fibroblast cell lines[1]. IDB-001 (10 μM; 2-8 h) induces a moderate ribotoxic stress response in MCF7 breast cancer cells: weak phosphorylation of JNK and p38 occurs after 2 h of treatment, while the integrated stress response is activated via eIF2α phosphorylation after 8 h of treatment[1].
References:
[1]. Diamond PD, et al. Context-dependent translation inhibition as a cancer therapeutic modality. Nat Commun. 2026;17(1):1963. Published 2026 Feb 24.
In Vitro, IDB-001 (10 μM; 60 min) induces translation elongation defects characterized by context-dependent stalling, preferentially targeting nascent polypeptide chains with an acidic residue at the -1 position, and elicits mild ribosome collisions upstream of stalling sites in HCC-1143 triple-negative breast cancer cells[1]. IDB-001 potently and specifically inhibits in vitro translation of reporter gene constructs containing acidic tetrameric sequences, exhibiting a biochemical selectivity window of at least 15-fold across different nascent peptide motifs. Its activity against the FTED motif is 3-fold higher than that of IDB-002, and its activity against the DDEY motif is 6-fold higher than that of IDB-002[1]. IDB-001 (50 μM; 30 min) induces a conformational change in the aspartic acid at position -1 of the nascent peptide chain to form a stable salt bridge, and triggers specific structural rearrangement of ribosomal RNA residues, thereby constricting the peptidyl transferase center and regulating the channel volume in human ribosome-nascent chain complexes containing MYC-derived QEDE peptides[1]. IDB-001 inhibits cancer cell proliferation, with an EC50 ranging from 0.663 μM (in HCC-1143 triple-negative breast cancer cells) to 5.440 μM (in MRC-5 fibroblasts). It exhibits the strongest activity against HCC-1143 cells among human cancer cell lines and fibroblast cell lines[1]. IDB-001 (10 μM; 2-8 h) induces a moderate ribotoxic stress response in MCF7 breast cancer cells: weak phosphorylation of JNK and p38 occurs after 2 h of treatment, while the integrated stress response is activated via eIF2α phosphorylation after 8 h of treatment[1].
References:
[1]. Diamond PD, et al. Context-dependent translation inhibition as a cancer therapeutic modality. Nat Commun. 2026;17(1):1963. Published 2026 Feb 24.