DiscoveryProbe™ FDA-approved Drug Library: High-Throughput Screening for Drug Repositioning and Target Identification

Executive Summary: The DiscoveryProbe™ FDA-approved Drug Library (L1021) by APExBIO offers 2,320 clinically approved, well-characterized bioactive compounds in ready-to-use DMSO solutions, supporting high-throughput screening (HTS) and high-content screening (HCS) for drug repositioning and pharmacological target identification (APExBIO). Each compound is approved by major regulatory agencies such as the FDA, EMA, HMA, CFDA, or PMDA. Mechanistic diversity is ensured, with compounds acting as enzyme inhibitors, receptor modulators, and pathway regulators. Representative drugs include doxorubicin, metformin, and atorvastatin. The library underpins translational research in oncology, neurodegenerative disease, and signal pathway analysis (Song et al., 2023).

Biological Rationale

The rapid identification of novel therapeutic targets and drug repositioning opportunities is a central challenge in translational biomedical research. FDA-approved drugs provide a privileged starting point for screening due to their established pharmacokinetic, safety, and mechanistic profiles (APExBIO). Repurposing existing drugs can bypass early-phase toxicity studies, reducing development time and cost. The DiscoveryProbe™ FDA-approved Drug Library leverages this approach by compiling 2,320 compounds approved by agencies such as the FDA, EMA, HMA, CFDA, and PMDA or listed in pharmacopeias. These compounds encompass a broad range of molecular targets and mechanisms, including enzyme inhibition, receptor modulation, and signal pathway regulation. Recent studies have demonstrated the value of such libraries for uncovering new roles for established drugs, such as the identification of carbenoxolone disodium as a histone deacetylase 6 (HDAC6) inhibitor with anti-gastric cancer effects (Song et al., 2023).

Mechanism of Action of DiscoveryProbe™ FDA-approved Drug Library

The DiscoveryProbe™ library comprises compounds with well-defined and diverse mechanisms of action. These include:

• Receptor Agonists and Antagonists: Modulate GPCRs, nuclear receptors, and ion channels.
• Enzyme Inhibitors: Target kinases, proteases, HDACs, and other enzyme classes.
• Ion Channel Modulators: Impact neuronal signaling and cardiac electrophysiology.
• Signal Pathway Regulators: Influence cellular signaling cascades such as EGFR, MAPK, and PI3K/AKT.

Each compound in the library is supplied at 10 mM in DMSO, enabling immediate use in cell-based and biochemical assays. Notably, the library includes drugs with pleiotropic mechanisms, facilitating the interrogation of complex biological processes and disease models (APExBIO).

Evidence & Benchmarks

• Carbenoxolone disodium, present in the DiscoveryProbe™ library, was identified as an HDAC6 inhibitor (IC₅₀ = 0.772 μM; K_D = 0.943 μM) using cellular thermal shift, surface plasmon resonance, and molecular docking assays (Song et al., 2023).
• Carbenoxolone disodium suppressed migration and proliferation of MGC-803 gastric cancer cells in vitro and in vivo (Song et al., 2023).
• The DiscoveryProbe™ FDA-approved Drug Library supports rapid pharmacological target identification, as demonstrated in oncology, neurodegeneration, and rare disease studies (internal article 1).
• Several HDAC inhibitors (e.g., vorinostat, romidepsin) included in the library are clinically approved for cancer therapy, validating the relevance of such compound collections for translational research (Song et al., 2023).
• Compounds remain stable for 12 months at -20°C and up to 24 months at -80°C in 10 mM DMSO solution (APExBIO).

This article extends the mechanistic focus of internal article 2 by providing clinical benchmarks and practical stability parameters for the DiscoveryProbe™ library.

Applications, Limits & Misconceptions

• Drug Repositioning Screening: The library enables systematic repurposing of FDA-approved drugs across diverse disease models (internal article 3 - this article provides updated real-world screening insights).
• Pharmacological Target Identification: Facilitates discovery of novel targets using phenotypic and mechanistic screens.
• Cancer Research Drug Screening: Supports oncology research, including target validation and signal pathway dissection.
• Neurodegenerative Disease Drug Discovery: Assists in identifying neuroprotective agents and modulators of neuronal signaling.
• Signal Pathway Regulation: Enables interrogation of key signaling nodes using pathway-specific compounds.

Common Pitfalls or Misconceptions

• The library is not suitable for de novo compound discovery; all molecules are pre-approved drugs.
• Compounds may not cover all rare or orphan disease targets.
• Results from high-throughput screens require secondary validation with orthogonal assays.
• Not all compounds are suitable for in vivo use without additional formulation or toxicity studies.
• Compound efficacy in cell-based assays does not guarantee clinical success due to differences in pharmacodynamics and pharmacokinetics.

Workflow Integration & Parameters

The DiscoveryProbe™ library is delivered as pre-dissolved 10 mM DMSO solutions in 96-well microplates, deep-well plates, or 2D barcoded screw-top tubes. This facilitates automated liquid handling for HTS and HCS platforms. Compounds can be dispensed directly into assay plates using robotic pipettors. Storage at -20°C provides up to 12 months of stability, while -80°C storage extends stability to 24 months. Shipping options include blue ice for evaluation samples and room temperature or blue ice for larger quantities. Recommended working concentrations vary by assay, typically ranging from 0.1 to 10 μM in cell-based screens. Quality control is performed using mass spectrometry or NMR to confirm compound identity and purity. Researchers should consider DMSO tolerance of their assay systems and include vehicle controls.

Conclusion & Outlook

The DiscoveryProbe™ FDA-approved Drug Library from APExBIO is a strategic tool for accelerating translational research and drug discovery. Its comprehensive coverage of clinically approved compounds, robust stability, and flexible formats make it suitable for diverse applications in oncology, neurodegeneration, and signal pathway analysis. Recent findings, such as the identification of carbenoxolone disodium as an HDAC6 inhibitor with anti-gastric cancer activity, illustrate the power of systematic drug repositioning enabled by such libraries (Song et al., 2023). For more details or to order the L1021 kit, visit the DiscoveryProbe™ FDA-approved Drug Library product page.