DiscoveryProbe™ FDA-approved Drug Library: Enabling High-Throughput Drug Repositioning and Mechanistic Screening

Executive Summary: The DiscoveryProbe™ FDA-approved Drug Library (L1021) is a validated collection of 2,320 bioactive compounds, each approved by at least one major regulatory agency (FDA, EMA, HMA, CFDA, PMDA), or listed in authoritative pharmacopeias (manufacturer data). These compounds represent a wide range of mechanisms, including receptor agonists/antagonists, enzyme inhibitors, and ion channel modulators. The library is optimized for high-throughput and high-content screening (HTS/HCS), with pre-dissolved 10 mM DMSO solutions ensuring consistency and stability for up to 24 months at -80°C. Recent peer-reviewed studies demonstrate that screening FDA-approved compound libraries enables rapid identification of repurposing candidates and novel targets in oncology, as shown by the discovery of adrenoceptor alpha-2 agonists enhancing carboplatin sensitivity in ovarian cancer models (Albanna et al., 2023). This resource facilitates translational workflows across cancer, neurodegeneration, and rare disease models.

Biological Rationale

The majority of disease-relevant targets are modulated by small molecules with established clinical profiles. Drug repositioning leverages the existing pharmacological and safety data of approved compounds to accelerate therapeutic discovery (Albanna et al., 2023). High-throughput screening (HTS) of FDA-approved drug libraries enables rapid identification of agents with unexpected activities in new indications (internal article). This approach is especially valuable in oncology, where acquired chemoresistance and tumor heterogeneity make de novo drug development slow and costly. The DiscoveryProbe™ FDA-approved Drug Library provides a systematic, mechanism-oriented tool for testing thousands of clinical agents against disease models, expediting the identification of new modulators of signaling pathways, apoptosis, and survival mechanisms. In neurodegenerative disease, this strategy can uncover agents that affect protein aggregation, synaptic plasticity, or neuronal survival with proven clinical tolerability (internal article).

Mechanism of Action of DiscoveryProbe™ FDA-approved Drug Library

The library contains 2,320 compounds with diverse, well-annotated mechanisms. These include:

• Receptor agonists and antagonists: e.g., adrenergic, muscarinic, dopaminergic, serotonergic, and GPCR-targeted drugs.
• Enzyme inhibitors: e.g., kinase inhibitors, protease inhibitors, and metabolic enzyme blockers.
• Ion channel modulators: e.g., calcium, sodium, potassium channel ligands.
• Signal pathway regulators: e.g., agents modulating PI3K/Akt, MAPK, and Wnt pathways.

Each compound is supplied as a 10 mM DMSO solution, ensuring solubility and compatibility with most cell-based and biochemical assays. The library supports both target-based (single protein or pathway) and phenotypic (cell/tissue-level) screening. For example, clonidine, an adrenoceptor alpha-2 agonist included in the library, was recently shown to sensitize ovarian cancer cells to carboplatin-induced cytotoxicity by promoting apoptosis (Albanna et al., 2023).

Evidence & Benchmarks

• HTS using an FDA-approved drug library identified six adrenoceptor alpha-2a (ADRA2A) agonists that enhance carboplatin cytotoxicity in ovarian cancer cell lines (Albanna et al., 2023, DOI).
• Validated in multiple ovarian cancer cell lines (TYKnu, CAOV3, OVCAR8) using two independent viability assays under standard culture conditions (37°C, 5% CO₂) (Albanna et al., 2023, DOI).
• Drug repositioning screens with clinically approved compound libraries have accelerated the identification of novel indications in oncology and neurodegeneration (internal article).
• Pre-dissolved 10 mM DMSO stock ensures compound stability for at least 12 months at -20°C and 24 months at -80°C, with QC provided by the manufacturer (product documentation).
• The library's format (96-well, deep well, or barcoded tubes) allows automation in HTS/HCS workflows, minimizing human error and batch-to-batch variability (product documentation).

Applications, Limits & Misconceptions

This FDA-approved bioactive compound library supports:

• High-throughput screening (HTS) for novel anti-cancer or neuroprotective agents.
• High-content phenotypic profiling (HCS) in disease model systems.
• Drug repositioning and combination therapy discovery.
• Mechanistic studies of signaling pathways and pharmacological targets.
• Assay validation and benchmarking with clinically relevant standards.

For comprehensive guidance on experimental design and troubleshooting, see this internal article, which the present review extends by providing updated peer-reviewed evidence and more detailed mechanistic context.

Common Pitfalls or Misconceptions

• The library is not suitable for de novo chemical diversity screening—compounds are all previously approved or listed in pharmacopeias.
• Hit validation requires secondary assays, as primary HTS can yield off-target or assay-specific effects.
• Not all compounds retain full activity in every cell type or assay format due to context-dependent pharmacodynamics.
• Solubility and DMSO tolerance must be monitored in sensitive cell-based assays.
• The library is not a substitute for patient-derived xenograft (PDX) or in vivo efficacy validation.

Workflow Integration & Parameters

The DiscoveryProbe™ FDA-approved Drug Library is designed for seamless integration into automated screening workflows. Key parameters include:

• Supplied as 10 mM DMSO stocks in 96-well, deep well plates, or 2D barcoded tubes for tracking.
• Recommended storage at -20°C (≤12 months) or -80°C (≤24 months) for maximum stability.
• Compatible with robotic liquid handling, multi-mode plate readers, and high-content imaging systems.
• QC documentation ensures traceability and batch consistency (product page).
• Shipping options include blue ice (evaluation samples) or room temperature/blue ice for larger sets.

For practical strategies to maximize screening success, see the analysis in this related article, which this review updates with new clinical and mechanistic benchmarks.

Conclusion & Outlook

The DiscoveryProbe™ FDA-approved Drug Library (L1021) represents a robust, validated platform for translational researchers aiming to accelerate drug repositioning, target identification, and mechanistic discovery in oncology, neurodegenerative, and rare diseases. Its regulatory-vetted compound set, optimized format, and proven utility in both basic and translational screens position it as a gold standard for high-throughput and high-content workflows. As new clinical and mechanistic data emerge, such libraries will remain central to precision medicine and rapid therapeutic innovation (Albanna et al., 2023).