Evidence map›Paper›PMID 37162961›Full record

ArticlebioRxiv : the preprint server for biology2023

Improving the solubility of pseudo-hydrophobic Alzheimer's Disease medicinal chemicals through co-crystal formulation.

A Tse, I Janilkarn-Urena, J Lin, X Chang, C Efthymiou, A Idrissova, M Zhang, C K Williams, S Magaki, H V Vinters and 4 more

Open access · greenAbstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in bioRxiv : the preprint server for biology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from 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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed, 1 citations in OpenAlex.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

14 authors at 3 institutions in 1 country.

A TseDepartment of Pharmacology and Pharmaceutical Sciences, University of Southern California Mann School of Pharmacy and Pharmaceutical Sciences, 1985 Zonal Ave, Los Angeles, CA 90089-9121, USA.
I Janilkarn-UrenaDepartment of Pharmacology and Pharmaceutical Sciences, University of Southern California Mann School of Pharmacy and Pharmaceutical Sciences, 1985 Zonal Ave, Los Angeles, CA 90089-9121, USA.
J LinDepartment of Biological Chemistry, University of California Los Angeles, 615 Charles E. Young Drive South, Los Angeles, CA 90095, USA.
X ChangDepartment of Pharmacology and Pharmaceutical Sciences, University of Southern California Mann School of Pharmacy and Pharmaceutical Sciences, 1985 Zonal Ave, Los Angeles, CA 90089-9121, USA.
C EfthymiouDepartment of Pharmacology and Pharmaceutical Sciences, University of Southern California Mann School of Pharmacy and Pharmaceutical Sciences, 1985 Zonal Ave, Los Angeles, CA 90089-9121, USA.
A IdrissovaDepartment of Pharmacology and Pharmaceutical Sciences, University of Southern California Mann School of Pharmacy and Pharmaceutical Sciences, 1985 Zonal Ave, Los Angeles, CA 90089-9121, USA.
M ZhangDepartment of Pharmacology and Pharmaceutical Sciences, University of Southern California Mann School of Pharmacy and Pharmaceutical Sciences, 1985 Zonal Ave, Los Angeles, CA 90089-9121, USA.
C K WilliamsDepartment of Pathology and Laboratory Medicine, David Geffen School of Medicine at University of California, Los Angeles, California 90095.
S MagakiDepartment of Pathology and Laboratory Medicine, David Geffen School of Medicine at University of California, Los Angeles, California 90095.
H V VintersDepartment of Pathology and Laboratory Medicine, David Geffen School of Medicine at University of California, Los Angeles, California 90095.
D L DaviesTitus Family Department of Clinical Pharmacy, University of Southern California School of Pharmacy, Los Angeles, CA 90089, USA.
T GonenDepartment of Biological Chemistry, University of California Los Angeles, 615 Charles E. Young Drive South, Los Angeles, CA 90095, USA.
H J GukasyanDepartment of Pharmacology and Pharmaceutical Sciences, University of Southern California Mann School of Pharmacy and Pharmaceutical Sciences, 1985 Zonal Ave, Los Angeles, CA 90089-9121, USA.
P M SeidlerDepartment of Pharmacology and Pharmaceutical Sciences, University of Southern California Mann School of Pharmacy and Pharmaceutical Sciences, 1985 Zonal Ave, Los Angeles, CA 90089-9121, USA.
University of Southern California · USUniversity of California, Los Angeles · USHoward Hughes Medical Institute · US

Funding

TRD4: Design and Engineering of MicroED hardware for nanocrystallization and time resolved studiesP41GM136508 · NIGMS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI EISENBERG, DAVID · 2020 to 2024
$7.6M
Towards Treatment of Alzheimer’s Disease by Targeting Pathogenic Tau and Beta-Amyloid StructuresR01AG070895 · NIA · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI DAVID EISENBERG · 2022 to 2026
$5.8M
Regulation of Alcohol Intake by Purinergic P2X4 ReceptorsR01AA022448 · NIAAA · UNIVERSITY OF SOUTHERN CALIFORNIA · PI DAVIES, DARYL L · 2013 to 2020
$2.9M
NIAAA NIH HHS R01 AA022448NIA NIH HHS R01 AG070895NIGMS NIH HHS P41 GM136508
6 · The paper itself

Abstract

Natural products are ligands and potential inhibitors of Alzheimer's disease (AD) tau. Dihydromyricetin (DHM) is a CNS active natural product. Despite having signature polyphenolic character, DHM is ostensibly hydrophobic owing to intermolecular hydrogen bonds that shield hydrophilic phenols. Our research shows DHM becomes ionized at near-neutral pH allowing formulation of salts with transformed solubility. The MicroED co-crystal structure with trolamine reveals DHM salts as metastable solids with unlocked hydrogen bonding and a thermodynamic bent to solubilize in water. All salt formulations show better inhibitory activity against AD tau than the non-salt form, with efficacies correlating to enhanced solubilities. These results underscore the role of structural chemistry in guiding selection of solubilizing agents for chemical formulation. We propose DHM salts are appropriate formulations for research as dietary supplements to promote healthy aging by combating protein misfolding. Additionally, DHM is a suitable lead for medicinal chemistry and possible development of CNS pharmaceuticals.

Identifiers

PMID37162961
PMCPMC10168350
OpenAlexW4367301410

What OpenQuestion holds

Textmetadata
LicenceCC BY-ND
Read underepoch 390

Registered trials

None linked

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.