OneHP Discovery:
Integrated Discovery Solutions for High Potent Therapeutics
Discovering highly-potent molecule (HP) demands a unique combination of scientific expertise, specialized containment infrastructure and early safety evaluation. Many emerging therapeutics — especially in oncology and targeted therapies — show very high biological activity, making accurate potency assessment and safe handling essential from the start.
Discovery Chemistry for Potent Molecules
Our medicinal chemistry team delivers agile, reliable synthesis through structured workflows designed for potent molecules and connected directly to downstream biology and analytics.
Chemistry Services
- Design and synthesis across multiple potent modalities (see Supported Modalities below)
- Structure–activity relationship to optimize potency, selectivity and developability, with rapid data turnaround to accelerate go/no-go decisions
- Scaffold optimization and analog generation
- Synthetic route feasibility assessment
Scale-Up Support
| Scale | Best suited for | Engagement model |
|---|---|---|
| 1mg to 1gm | Early discovery and profiling | Fee-for-service (FFS) |
| 5gm to 50gm | Expanded discovery and development projects | Full-time equivalent (FTE) or FFS |
Supported HP Modalities
| Modality | Examples |
|---|---|
| Small molecules | Small-molecule cytotoxics, kinase inhibitors, natural product scaffolds, steroids, prostaglandins |
| ADC Payloads & Linkers | Auristatins, maytansinoids, PBDs, Exatecan and Duocarmycins •Non-Cleavable Linkers •Cleavable Linkers •Chemically Labile Linkers |
| Targeted protein degraders | PROTACs, molecular glues |
| Peptides & peptidomimetics | Potent peptides; Cyclic peptides and stapled/constrained peptides |
| Oligonucleotides | Antisense, siRNA, miRNA constructs |
Potency, Biological & Mechanistic Evaluation
Understanding potency early enables informed decisions and sets the right containment strategy. Our integrated assay platforms characterize biological activity, target engagement and mechanism — guiding optimization, candidate selection and preclinical planning.
| Assay platform | What we measure |
|---|---|
| Biochemical assays | Enzyme inhibition, receptor binding, target-specific kinase and enzymatic activity, kinase profiling, SPR kinetics |
| In vitro potency & binding | IC₅₀, EC₅₀ and binding affinity |
| Cell-based functional assays | Cytotoxicity and selectivity profiling; viability, cell cycle and apoptosis profiling; clonogenic studies |
| Immune effector function assays | ADCC, ADCP, CDC |
| High-content imaging | Receptor internalization, lysosomal trafficking, mitochondrial toxicity |
Safety & Hazard Assessment for OEB Classification
Safe progression of potent molecules starts with early pharmacological and toxicological evaluation. Our hazard assessments support accurate Occupational Exposure Band (OEB) classification & evaluation, so the right containment and safety controls are in place. Assessments cover:
- Pharmacological activity and receptor affinity, through in vitro binding and functional assays
- Genotoxicity and mutagenicity — Ames test and micronucleus assay
- Carcinogenicity risk indicators associated with long-term exposure
- Reproductive and developmental toxicity
- Acute toxicity indicators — dose-range finding and lethal dose range estimation
- Repeat-dose toxicity to identify potential target-organ effects
Analytical Characterization
Compounds advancing toward preclinical studies are well understood for identity, purity and stability. All analytical workflows are fully validated, traceable and compliant with regulatory standards.
- HP molecule and payload quantification: LC-MS/MS, HRMS and triple quadrupole (QQQ) mass spectrometry
- Purity, aggregation and thermal stability assessment
- Solid-state characterization: polymorphism analysis and stability evaluation under strict containment, supporting long-term drug product viability
- ADC-specific analytics, including drug-to-antibody ratio (DAR) determination
- Antibody and conjugate characterization: ELISA, MSD, SPR
- Payload release and metabolite profiling
ADME, PK/PD & Preclinical Studies
Integrated ADME and preclinical capabilities for conjugate, antibody and payload entities deliver robust, reliable data for safe and informed candidate progression.
- In vitro ADME: buffer stability, lysosomal cleavage, permeability, efflux, DAR analysis and metabolite profiling
- Bioanalytical support: quantitative measurement on LC-MS/MS, HRMS, ELISA and MSD platforms
- In vivo PK/PD: rodent and non-rodent exposure–response evaluations
- Preclinical efficacy and safety: proof-of-concept and tolerability assessment
ADC & Bioconjugation Integration
For ADC programs, Aragen seamlessly connects biologics discovery with high-potency payload development:
- Antibody discovery and engineering
- Bioconjugation: chemical and enzymatic conjugation; purification
- ADC characterization: concentration, DAR, aSE-HPLC, SDS-PAGE, thermal stability, antigen binding
Containment, Handling, and Cleaning
Our discovery facilities are designed to safely manage compounds within OEB-6 containment standards (OEL up to 10ng/m³), protecting personnel, the environment and product integrity across every workflow.
Containment Infrastructure
- Isolator-based handling systems, gloveboxes uni-directional flow and restricted access barrier systems (RABS)
- Restricted laminar airflow (RLAF) environments and Class II – B2 biological safety cabinets
- Dedicated HVAC for process and non-process with HEPA filtration and Bag-In/Bag-Out (BIBO) protocols to prevent cross-contamination
Operational Controls
- Controlled workflows for weighing, dispensing, solubilization and intermediate preparation
- Specialized automation for potent-compound handling
- Restricted access areas, specialized PPE and comprehensive personnel training
Cleaning and Environmental Controls
- Validated cleaning procedures for potent-compound environments
- Dedicated waste management streams
- Environmental monitoring programs and containment verification
Why Aragen for High Potent Molecule Discovery
- Integrated ecosystem: Chemistry, biology and analytics under one roof
- Safe containment: OEB-6 infrastructure with validated workflows
- High potent expertise: Cytotoxics, ADC payloads, kinase inhibitors and more
- Analytical rigor: From LC-MS/MS to antibody–payload characterization
- Single-site: Discovery through preclinical evaluation
Related Links
OneHP Development & Manufacturing
Aragen reliably develops and manufactures high-potency APIs, including cytotoxics, drug linkers, PEG conjugations, and ADC toxins, ensuring safe, effective solutions.
