Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

Related Concept Videos

Preclinical Development: Overview01:28

Preclinical Development: Overview

5.7K
Preclinical development consists of a series of tests that ensure the safety and efficacy of a new therapeutic compound before it is tested in humans. There are four main phases to this process. First, safety pharmacology tests are conducted to ensure the drug does not produce any acutely harmful effects. These tests examine parameters such as bronchoconstriction, cardiac dysrhythmias, blood pressure changes, and ataxia. Next, preliminary toxicological testing is performed to determine the...
5.7K
Clinical Trials: Overview01:11

Clinical Trials: Overview

4.5K
Clinical development focuses on how the drug will interact with the human body and encompasses four key phases of clinical trials, each serving a specific purpose in assessing the safety and effectiveness of new drugs. These phases overlap and build upon one another. Phase I involves a small group of healthy volunteers (typically 20-80 individuals) or, in cases where significant toxicity is expected, patients with the targeted disease, such as cancer or AIDS. The volunteers are tested for...
4.5K
Drug Discovery: Overview01:26

Drug Discovery: Overview

10.9K
Drug discovery is a multifaceted process involving extensive screening, testing, and optimization of lead compounds to identify potential new drugs for therapeutic use. It combines several approaches, including screening large numbers of natural products, chemical modification of known active molecules, identification of new drug targets, and rational design based on biological mechanisms and drug-receptor structure. These approaches are carried out in both academic research laboratories and...
10.9K
Drug Administration and Therapy Phases: Overview01:26

Drug Administration and Therapy Phases: Overview

1.1K
Drugs, the chemical agents used in diagnosing, treating, or preventing diseases, undergo a four-phase process of development: pharmaceutic, pharmacokinetics, pharmacodynamics, and therapeutic.
The pharmaceutical phase focuses on leveraging the physicochemical properties of the drug to design and manufacture an effective product. Variants include orally administered tablets or capsules, topical creams or ointments, and parenteral-delivery solutions or emulsions.
The pharmacokinetic phase...
1.1K
In Vitro Drug Release Testing: Overview, Development and Validation01:10

In Vitro Drug Release Testing: Overview, Development and Validation

279
In vitro dissolution and drug release tests assess how quickly and how much of a drug is released from its dosage form into an aqueous medium under standardized laboratory conditions. These tests are essential tools in pharmaceutical development and quality assurance, offering insight into the drug's performance before clinical use.During formulation development, dissolution testing identifies incomplete or inconsistent drug release issues. It also supports decisions on selecting the optimal...
279
Drug Regulation01:25

Drug Regulation

2.7K
Drug regulation encompasses the management of drug usage by evaluating its safety and efficacy through assessments conducted by regulatory authorities. Regrettably, the history of drug regulation is marred by several catastrophic events. One such incident is the Elixir Sulfanilamide tragedy, in which the toxic compound diethyl glycol was included in a sweet-tasting medication, leading to numerous fatalities. This event prompted the enactment of the Food, Drug, and Cosmetic Act in 1938. Under...
2.7K

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by
Same author

Discovery of a CI-994 derivative as a dual modulator of class I HDACs and Wnt/β- catenin signaling for Alzheimer's disease therapy.

bioRxiv : the preprint server for biology·2026
Same author

Alzheimer disease protection from the periphery.

Nature reviews. Neurology·2026
Same author

Association of plasma glial fibrillary acidic protein and APOE-ε4 with Alzheimer's disease.

Neurobiology of aging·2026
Same author

Astrocytic APOE3-Christchurch expression ameliorates brain amyloid-β pathology in 5xFAD mice.

Translational psychiatry·2026
Same author

Sex-specific APOE4-dependent innate immunity regulates meningeal lymphatics, brain lipids, neuroinflammation, and cognition.

Neuron·2026
Same author

Molecular characterization of humanized APOE mouse models reveals source and genotype dependent differences.

Molecular neurodegeneration·2026

Related Experiment Video

Updated: Jan 7, 2026

Drug Repurposing Hypothesis Generation Using the "RE:fine Drugs" System
05:10

Drug Repurposing Hypothesis Generation Using the "RE:fine Drugs" System

Published on: December 11, 2016

10.1K

Drug Development.

Wenyan Lu1, Thomas R Caulfield1, Suren Jeevaratnam1

  • 1Mayo Clinic, Jacksonville, FL, USA.

Alzheimer'S & Dementia : the Journal of the Alzheimer'S Association
|December 25, 2025
PubMed
Summary
This summary is machine-generated.

A novel dual-acting drug candidate, W2A-28, simultaneously targets histone deacetylase (HDAC) inhibition and Wnt/β-catenin signaling activation. This compound shows promise for Alzheimer's disease (AD) treatment by reducing amyloid-beta and tau pathologies.

More Related Videos

In Vitro Three-Dimensional Sprouting Assay of Angiogenesis Using Mouse Embryonic Stem Cells for Vascular Disease Modeling and Drug Testing
08:04

In Vitro Three-Dimensional Sprouting Assay of Angiogenesis Using Mouse Embryonic Stem Cells for Vascular Disease Modeling and Drug Testing

Published on: May 11, 2021

3.3K
Developmental Toxicity Assay Based on Real-Time Monitoring of Fibroblast Growth Factor Signal Disruption in Human Induced Pluripotent Stem Cells
05:45

Developmental Toxicity Assay Based on Real-Time Monitoring of Fibroblast Growth Factor Signal Disruption in Human Induced Pluripotent Stem Cells

Published on: October 10, 2025

451

Related Experiment Videos

Last Updated: Jan 7, 2026

Drug Repurposing Hypothesis Generation Using the "RE:fine Drugs" System
05:10

Drug Repurposing Hypothesis Generation Using the "RE:fine Drugs" System

Published on: December 11, 2016

10.1K
In Vitro Three-Dimensional Sprouting Assay of Angiogenesis Using Mouse Embryonic Stem Cells for Vascular Disease Modeling and Drug Testing
08:04

In Vitro Three-Dimensional Sprouting Assay of Angiogenesis Using Mouse Embryonic Stem Cells for Vascular Disease Modeling and Drug Testing

Published on: May 11, 2021

3.3K
Developmental Toxicity Assay Based on Real-Time Monitoring of Fibroblast Growth Factor Signal Disruption in Human Induced Pluripotent Stem Cells
05:45

Developmental Toxicity Assay Based on Real-Time Monitoring of Fibroblast Growth Factor Signal Disruption in Human Induced Pluripotent Stem Cells

Published on: October 10, 2025

451

Area of Science:

  • Neuroscience
  • Pharmacology
  • Molecular Biology

Background:

  • Alzheimer's disease (AD) involves impaired histone acetylation and Wnt/β-catenin signaling.
  • Targeting multiple pathologies, like with dual modulators, may offer synergistic effects for AD.
  • Class I histone deacetylase (HDAC) inhibitors and Wnt/β-catenin pathway activators are potential AD therapeutics.

Purpose of the Study:

  • To develop novel dual modulators targeting class I HDAC inhibition and Wnt/β-catenin signaling activation.
  • To evaluate the therapeutic potential of the lead compound W2A-28 in Alzheimer's disease (AD) models.

Main Methods:

  • Utilized CI-994 as a scaffold to design dual-acting compounds.
  • Assessed W2A-28's inhibitory activity against class I HDACs and its effect on Wnt reporter activity.
  • Determined W2A-28's impact on LRP6 protein levels, solubility, stability, and permeability.
  • Tested W2A-28 in patient-derived induced pluripotent stem cell (iPSC)-derived cerebral organoids.

Main Results:

  • W2A-28 potently inhibited class I HDAC1, 2, and 3 with nanomolar IC50 values.
  • W2A-28 activated Wnt/β-catenin signaling by increasing Wnt reporter activity and stabilizing LRP6.
  • The compound exhibited favorable pharmacokinetic properties, including good solubility, stability, and permeability.
  • W2A-28 significantly reduced amyloid-beta (Aβ40, Aβ42) levels and suppressed tau phosphorylation in AD organoids.

Conclusions:

  • W2A-28 demonstrates dual inhibitory and activating properties relevant to AD pathology.
  • The compound effectively reduced key Alzheimer's disease biomarkers in patient-derived organoids.
  • W2A-28 represents a promising drug candidate for Alzheimer's disease treatment.