ArticleACS medicinal chemistry letters2024
Toward Dual Targeting of Catalytic and Gatekeeper Pockets in Cyclophilins Using a Macrocyclic Scaffold.
Article in ACS medicinal chemistry letters, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
What it found
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
1 citing paper in PubMed.
- Nondegradative Synthetic Molecular Glues Enter the Clinic.ChemMedChem · 2025Review
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Authors and funding
3 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cyclophilins, especially cyclophilin A, are involved in a variety of diseases, including the life cycle of many viruses. An advanced macrocyclic inhibitor of cyclophilin was reported to bind the catalytic pocket but not the neighboring gatekeeper pocket. Here we describe macrocyclic cyclophilin inhibitors bearing side chains designed to reach out to the gatekeeper pocket. After establishing a suitable synthesis allowing for late-stage modification of the relevant positions, we explored this exit vector. This culminated in a rigid ornithine-resembling analogue as a versatile building block, which was also incorporated into the macrocyclic scaffold. The use of amines as the gatekeeper-engaging modality was invalidated, but the exit vector was successfully established as a promising position for future modifications. Further work is needed to identify suitable motifs to simultaneously engage the catalytic and gatekeeper pockets in this highly developed macrocyclic scaffold.
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Registered trials
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