ReviewMolecules (Basel, Switzerland)2020
Second-Generation Pharmacological Chaperones: Beyond Inhibitors.
Review in Molecules (Basel, Switzerland), 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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
28 citing papers in PubMed.
- Development of Small-Molecule Allosteric Modulators of Beta-Galactosidase (β-Gal) for the Treatment of GM1 Gangliosidosis and Morquio B.International journal of molecular sciences · 2026Article
- Microwave-Assisted Synthesis and Enzyme Stabilization Study ofACS omega · 2026Article
- Osteoarthritis: molecular pathogenesis and potential therapeutic options.Signal transduction and targeted therapy · 2026Review
- Functional assessment of protein variants in structured domains by fluorescence cross-correlation spectroscopy.Scientific reports · 2026Article
- The function of chaperones in the radioresistance of glioblastoma: a new insight into the current knowledge.Brain tumor pathology · 2025Review
- Developing nanobodies as allosteric molecular chaperones of glucocerebrosidase function.Nature communications · 2025Article
- Novel Treatment Strategy for Patients With Urea Cycle Disorders: Pharmacological Chaperones Enhance Enzyme Stability and Activity in Patient-Derived Liver Disease Models.Journal of inherited metabolic disease · 2025Article
- Phenylbutyric Acid Modulates Apoptosis and ER Stress-Related Gene Expression in Glycogen Storage Disease Type Ib In Vitro Model.Molecular genetics & genomic medicine · 2025Article
- Use of the Novel Site-Directed Enzyme Enhancement Therapy (SEE-Tx) Drug Discovery Platform to Identify Pharmacological Chaperones for Glutaric Acidemia Type 1.Journal of medicinal chemistry · 2024Article
- Discovery of Novel Inhibitors against ALS-Related SOD1(A4V) Aggregation through the Screening of a Chemical Library Using Differential Scanning Fluorimetry (DSF).Pharmaceuticals (Basel, Switzerland) · 2024Article
- Gaucher Disease Coexisting with Cytomegalovirus Infection: A Rare Presentation in an Infant.The American journal of case reports · 2024Article
- Protein aggregation and therapeutic strategies in SOD1- and TDP-43- linked ALS.Frontiers in molecular biosciences · 2024Review
- GBA1 Variants and Parkinson's Disease: Paving the Way for Targeted Therapy.Journal of movement disorders · 2023Article
- Potential Binding Sites of Pharmacological Chaperone NCGC00241607 on Mutant β-Glucocerebrosidase and Its Efficacy on Patient-Derived Cell Cultures in Gaucher and Parkinson's Disease.International journal of molecular sciences · 2023Article
- A mutation in DOK7 in congenital myasthenic syndrome forms aggresome in cultured cells, and reduces DOK7 expression and MuSK phosphorylation in patient-derived iPS cells.Human molecular genetics · 2023Article
- Biochemical Characteristics of iPSC-Derived Dopaminergic Neurons from N370SInternational journal of molecular sciences · 2023Article
- [Advances in the diagnosis and treatment of phosphomannomutase 2 deficiency].Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics · 2023Review
- Recent therapeutic approaches to cystathionine beta-synthase-deficient homocystinuria.British journal of pharmacology · 2023Review
- Validation of a highly sensitive HaloTag-based assay to evaluate the potency of a novel class of allosteric β-Galactosidase correctors.PloS one · 2023Article
- spJournal of enzyme inhibition and medicinal chemistry · 2022Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Protein misfolding induced by missense mutations is the source of hundreds of conformational diseases. The cell quality control may eliminate nascent misfolded proteins, such as enzymes, and a pathological loss-of-function may result from their early degradation. Since the proof of concept in the 2000s, the bioinspired pharmacological chaperone therapy became a relevant low-molecular-weight compound strategy against conformational diseases. The first-generation pharmacological chaperones were competitive inhibitors of mutant enzymes. Counterintuitively, in binding to the active site, these inhibitors stabilize the proper folding of the mutated protein and partially rescue its cellular function. The main limitation of the first-generation pharmacological chaperones lies in the balance between enzyme activity enhancement and inhibition. Recent research efforts were directed towards the development of promising second-generation pharmacological chaperones. These non-inhibitory ligands, targeting previously unknown binding pockets, limit the risk of adverse enzymatic inhibition. Their pharmacophore identification is however challenging and likely requires a massive screening-based approach. This review focuses on second-generation chaperones designed to restore the cellular activity of misfolded enzymes. It intends to highlight, for a selected set of rare inherited metabolic disorders, the strategies implemented to identify and develop these pharmacologically relevant small organic molecules as potential drug candidates.
Indexed as
Identifiers
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.