ArticleBioorganic & medicinal chemistry2019
Synthesis and evaluation of esterified Hsp70 agonists in cellular models of protein aggregation and folding.
Article in Bioorganic & medicinal chemistry, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 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
15 citing papers in PubMed, 21 citations in OpenAlex.
- Assays to measure small molecule Hsp70 agonist activity in vitro and in vivo.Analytical biochemistry · 2025Article
- Co-chaperones fine-tune the function of heat shock protein 70 (Hsp70), whether to fold, hold, or degrade substrates in ensuring cellular protein homeostasis.Journal of biosciences · 2025Review
- J-domain proteins: From molecular mechanisms to diseases.Cell stress & chaperones · 2024Article
- Linking Heat Shock Protein 70 and Parkin in Parkinson's Disease.Molecular neurobiology · 2023Review
- Disrupting pathologic phase transitions in neurodegeneration.The Journal of clinical investigation · 2023Review
- Molecular Chaperones' Potential against Defective Proteostasis of Amyotrophic Lateral Sclerosis.Cells · 2023Review
- Second Virtual International Symposium on Cellular and Organismal Stress Responses, September 8-9, 2022.Cell stress & chaperones · 2023Article
- Role of Proteostasis Regulation in the Turnover of Stress Granules.International journal of molecular sciences · 2022Review
- Proteostasis Regulators in Cystic Fibrosis: Current Development and Future Perspectives.Journal of medicinal chemistry · 2022Review
- Chemical Chaperones to Inhibit Endoplasmic Reticulum Stress: Implications in Diseases.Drug design, development and therapy · 2022Review
- Heat Shock Protein 70 as a Sex-Skewed Regulator of α-Synucleinopathy.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2021Article
- Improved correction of F508del-CFTR biogenesis with a folding facilitator and an inhibitor of protein ubiquitination.Bioorganic & medicinal chemistry letters · 2021Article
- Synthesis and Selective Functionalization of Thiadiazine 1,1-Dioxides with Efficacy in a Model of Huntington's Disease.ACS medicinal chemistry letters · 2020Article
- Hsp70 and the Unfolded Protein Response as a Challenging Drug Target and an Inspiration for Probe Molecule Development.ACS medicinal chemistry letters · 2020Article
- Neutral analogs of the heat shock protein 70 (Hsp70) inhibitor, JG-98.Bioorganic & medicinal chemistry letters · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
14 authors at 2 institutions in 3 countries.
Funding
Abstract
Over-expression of the Hsp70 molecular chaperone prevents protein aggregation and ameliorates neurodegenerative disease phenotypes in model systems. We identified an Hsp70 activator, MAL1-271, that reduces α-synuclein aggregation in a Parkinson's Disease model. We now report that MAL1-271 directly increases the ATPase activity of a eukaryotic Hsp70. Next, twelve MAL1-271 derivatives were synthesized and examined in a refined α-synuclein aggregation model as well as in an assay that monitors maturation of a disease-causing Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) mutant, which is also linked to Hsp70 function. Compared to the control, MAL1-271 significantly increased the number of cells lacking α-synuclein inclusions and increased the steady-state levels of the CFTR mutant. We also found that a nitrile-containing MAL1-271 analog exhibited similar effects in both assays. None of the derivatives exhibited cellular toxicity at concentrations up to 100 μm, nor were cellular stress response pathways induced. These data serve as a gateway for the continued development of a new class of Hsp70 agonists with efficacy in these and potentially other disease models.
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.