ArticleACS medicinal chemistry letters2015
Structure-Activity Study of Bioisosteric Trifluoromethyl and Pentafluorosulfanyl Indole Inhibitors of the AAA ATPase p97.
Article in ACS medicinal chemistry letters, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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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
26 citing papers in PubMed, 50 citations in OpenAlex.
- A genome-scale drug discovery pipeline uncovers new therapeutic targets and a unique p97 allosteric binding site inbioRxiv : the preprint server for biology · 2025Article
- Mechanism of allosteric inhibition of human p97/VCP ATPase and its disease mutant by triazole inhibitors.Communications chemistry · 2024Article
- Optimization of 1,2,4-Triazole-Based p97 Inhibitors for the Treatment of Cancer.ACS medicinal chemistry letters · 2023Article
- Molecular Mechanisms Driving and Regulating the AAA+ ATPase VCP/p97, an Important Therapeutic Target for Treating Cancer, Neurological and Infectious Diseases.Biomolecules · 2023Review
- Fragment screening using biolayer interferometry reveals ligands targeting the SHP-motif binding site of the AAA+ ATPase p97.Communications chemistry · 2022Article
- NMS-873 Leads to Dysfunctional Glycometabolism in A p97-Independent Manner in HCT116 Colon Cancer Cells.Pharmaceutics · 2022Article
- Temporal proteomics reveal specific cell cycle oncoprotein downregulation by p97/VCP inhibition.Cell chemical biology · 2022Article
- Synthesis and Physicochemical Properties of 2-SFACS organic & inorganic Au · 2021Article
- Valosin-Containing Protein (VCP)/p97: A Prognostic Biomarker and Therapeutic Target in Cancer.International journal of molecular sciences · 2021Review
- Affinity Capture of p97 with Small-Molecule Ligand Bait Reveals a 3.6 Å Double-Hexamer Cryoelectron Microscopy Structure.ACS nano · 2021Article
- Chemical modulation of Kv7 potassium channels.RSC medicinal chemistry · 2021Review
- Enzyme Replacement Therapy for Mucopolysaccharidosis IIID using Recombinant Human α-Molecular pharmaceutics · 2021Article
- Allosteric p97 Inhibitors Can Overcome Resistance to ATP-Competitive p97 Inhibitors for Potential Anticancer Therapy.ChemMedChem · 2020Article
- Synthesis and Optimization of KACS medicinal chemistry letters · 2019Article
- Optimization of Phenyl Indole Inhibitors of the AAA+ ATPase p97.ACS medicinal chemistry letters · 2018Article
- Emerging Cancer Therapeutic Targets in Protein Homeostasis.The AAPS journal · 2018Article
- Discovery of DEBIC to correlate P-selectin inhibition and DNA intercalation in cancer therapy and complicated thrombosis.Oncotarget · 2018Article
- The AAA+ ATPase p97, a cellular multitool.The Biochemical journal · 2017Review
- Dichlorotrifluoromethoxyacetic Acid: Preparation and Reactivity.Molecules (Basel, Switzerland) · 2017Article
- A threonine turnstile defines a dynamic amphiphilic binding motif in the AAA ATPase p97 allosteric binding site.Organic & biomolecular chemistry · 2017Article
Corrections and comments
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Authors and funding
14 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Exploratory SAR studies of a new phenyl indole chemotype for p97 inhibition revealed C-5 indole substituent effects in the ADPGlo assay that did not fully correlate with either electronic or steric factors. A focused series of methoxy-, trifluoromethoxy-, methyl-, trifluoromethyl-, pentafluorosulfanyl-, and nitro-analogues was found to exhibit IC50s from low nanomolar to double-digit micromolar. Surprisingly, we found that the trifluoromethoxy-analogue was biochemically a better match of the trifluoromethyl-substituted lead structure than a pentafluorosulfanyl-analogue. Moreover, in spite of their almost equivalent strongly electron-depleting effect on the indole core, pentafluorosulfanyl- and nitro-derivatives were found to exhibit a 430-fold difference in p97 inhibitory activities. Conversely, the electronically divergent C-5 methyl- and nitro-analogues both showed low nanomolar activities.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.