ArticleChemistry (Weinheim an der Bergstrasse, Germany)2022
Unprecedented Combination of Polyketide Natural Product Fragments Identifies the New Hedgehog Signaling Pathway Inhibitor Grismonone.
Article in Chemistry (Weinheim an der Bergstrasse, Germany), 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed.
- Pseudonatural Products for Chemical Biology and Drug Discovery.Journal of medicinal chemistry · 2025Review
- An Indole Dearomatization Strategy for the Synthesis of Pseudo-Natural Products.Chembiochem : a European journal of chemical biology · 2025Article
- A divergent intermediate strategy yields biologically diverse pseudo-natural products.Nature chemistry · 2024Article
- Thermo-Structural Characterization of Phase Transitions in Amorphous Griseofulvin: From Sub-TMolecules (Basel, Switzerland) · 2024Article
- A highly enantioselective intramolecular 1,3-dipolar cycloaddition yields novel pseudo-natural product inhibitors of the Hedgehog signalling pathway.Chemical science · 2023Article
- Unprecedented Combination of Polyketide Natural Product Fragments Identifies the New Hedgehog Signaling Pathway Inhibitor Grismonone.Chemistry (Weinheim an der Bergstrasse, Germany) · 2022Article
Corrections and comments
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Authors and funding
10 authors.
Funding
Abstract
Pseudo-natural products (pseudo-NPs) are de novo combinations of natural product (NP) fragments that define novel bioactive chemotypes. For their discovery, new design principles are being sought. Previously, pseudo-NPs were synthesized by the combination of fragments originating from biosynthetically unrelated NPs to guarantee structural novelty and novel bioactivity. We report the combination of fragments from biosynthetically related NPs in novel arrangements to yield a novel chemotype with activity not shared by the guiding fragments. We describe the synthesis of the polyketide pseudo-NP grismonone and identify it as a structurally novel and potent inhibitor of Hedgehog signaling. The insight that the de novo combination of fragments derived from biosynthetically related NPs may also yield new biologically relevant compound classes with unexpected bioactivity may be considered a chemical extension or diversion of existing biosynthetic pathways and greatly expands the opportunities for exploration of biologically relevant chemical space by means of the pseudo-NP principle.
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Registered trials
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