ArticleCell chemical biology2021
Evolution of kinase polypharmacology across HSP90 drug discovery.
Article in Cell chemical biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
10 citing papers in PubMed, 1 synthesis or guideline pooled it, 23 citations in OpenAlex.
- Systematic Analysis of Covalent and Allosteric Protein Kinase Inhibitors.Molecules (Basel, Switzerland) · 2023Pooled it
- FirstResearch square · 2026Article
- Target Class Repurposing Across Membrane Transporter Families Provides Privileged Ligands to Address Specific and Undruggable Pharmacological Targets.ACS pharmacology & translational science · 2026Article
- Individualized Pooled CRISPR/Cas9 Screenings Identify CDK2 as a Druggable Vulnerability in a Canine Mammary Carcinoma Patient.Veterinary sciences · 2025Article
- Hiding in plain sight: Optimizing topoisomerase IIα inhibitors into Hsp90β selective binders.European journal of medicinal chemistry · 2024Article
- A fluorescence-based sensor for calibrated measurement of protein kinase stability in live cells.Protein science : a publication of the Protein Society · 2024Article
- Drug resistance mechanisms in cancers: Execution of pro-survival strategies.Journal of biomedical research · 2024Article
- A Fluorescence-Based Sensor for Calibrated Measurement of Protein Kinase Stability in Live Cells.bioRxiv : the preprint server for biology · 2023Article
- NMS-873 Leads to Dysfunctional Glycometabolism in A p97-Independent Manner in HCT116 Colon Cancer Cells.Pharmaceutics · 2022Article
- Design and Synthesis of Hsp90 Inhibitors with B-Raf and PDHK1 Multi-Target Activity.ChemistryOpen · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Most small molecules interact with several target proteins but this polypharmacology is seldom comprehensively investigated or explicitly exploited during drug discovery. Here, we use computational and experimental methods to identify and systematically characterize the kinase cross-pharmacology of representative HSP90 inhibitors. We demonstrate that the resorcinol clinical candidates ganetespib and, to a lesser extent, luminespib, display unique off-target kinase pharmacology as compared with other HSP90 inhibitors. We also demonstrate that polypharmacology evolved during the optimization to discover luminespib and that the hit, leads, and clinical candidate all have different polypharmacological profiles. We therefore recommend the computational and experimental characterization of polypharmacology earlier in drug discovery projects to unlock new multi-target drug design opportunities.
Indexed as
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What OpenQuestion holds
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.