Better ScienceFor Drug Discovery

Target Identification & Validation

Excellerate specialize in developing validation packages across various target classes and therapeutic areas.

Services available within our target validation packages include:

• Expression profiling performed at mRNA and protein level (qPCR, flow cytometry, Western analysis, immunofluorescence imaging)

• Phenotypic assays in primary cells to assess target function

• Libraries of known pathway modulators and approved drugs

• Recombinant target tool generation

• siRNA/nucleofection target validation in primary cells

• Biomarker identification and validation

• Binding assays (HTRF, TR-FRET, BRET)

Lead Identification

Excellerate provide the expertise and support required to perform efficient hit-to-lead projects in a timely manner for progression to lead series.

• Comprehensive assay development spanning diverse targets and formats

• MTS/HTS focused library screening

• Orthogonal assays to eliminate false positives

• Mechanism of action, SAR and target engagement studies

We are proficient at managing third-party and custom compound libraries and can profile in vitro HTS cascades (100k+ compound) down to single molecules for comprehensive mechanistic studies covering:

• Phenotypic screening by single molecule & synergistic studies, cell and species selectivity panels, viability & cytotoxicity assays

• Functional cellular, biochemical and high-definition kinetics (association/dissociation)

• Biophysical quantification of target engagement 

Lead Optimization

At Excellerate, we provide full support for lead optimization, to transform lead molecules into preclinical candidates.

Based on discussion cycles with clients led by our senior scientific team, Excellerate develop optimal screening strategies, selecting assays tailored to the drug class, target, and indication, advising on pharmacological design.

• Compound profiling with robust assay validation
• Assay automation to boost experimental throughput
• Integration with client data management
• Compound management with third parties

Our efficient screening, analysis, and reporting workflows minimize iteration times, whilst maintaining accuracy. We actively participate in project meetings, offering expert advice on in vitro pharmacology. Additionally, we provide ongoing support for client milestones, with flexible costing approaches.

Pre-Clinical Candidate Studies

Excellerate provide in-depth mechanistic characterization of drug candidates, supporting clinical data interpretation and competitive profiling.

Our expertise extends to developing comprehensive preclinical publication strategies, integrating phenotypic screening, synergy matrix studies, and advanced cell-based assays.

• Phenotypic screening

• Mechanism of action studies

• Toxicology/cytotoxicity assays

• Competitor compound profiling

• Publication strategies

Screening & Assay Development

Excellerate has capabilities to deliver library screening for hit identification through to routine weekly support of lead optimisation projects.

• Compound profiling with robust assay validation

• Assay automation to boost throughput

• Integration with client data management

• Compound management with third parties

Our tailored approach to assay data handling, analysis and reporting ensures alignment with your specific assay requirements across all in vitro assay screening including:

• Cellular, biochemical and kinetic assay screening

• Iterative screening

• Screening libraries (MTS/HTS; 100k+ compounds)

Therapeutic Areas

Excellerate has capabilities across multiple disease areas, with successful track records in therapeutic drug discovery fields including, but not limited to;

• Cardiovascular

• Respiratory

• Metabolic disease

• Immunology

• Oncology

• CNS

• Inflammation

Our precision-driven approach aims to address the unique challenges that each disease area poses. We closely align with your program requirements and tailor our scientific support to drive your research forward.

Drug Modalities

Excellerate's expertise across diverse modalities can support you in unlocking the potential of your drug candidates.

• LMw and Biologics: Tailored strategies to optimize efficacy and safety

• Orthosteric/Allosteric Interactions: Comprehensive analyses of drug-target interactions and mode of action

• Kinetics and Covalent Inhibitors: Expertise in kinetics for targeted intervention and duration

• Innovative Biologics: Bispecific antibodies, BiTEs, and ligand-directed therapies

• Next-Generation Therapies: PROTACs, molecular glues, and novel drug delivery systems

• Advanced Therapeutic Approaches: Prodrugs, immunomodulators, and synergistic combinations

Molecular Pharmacology

Excellerate is internationally recognized for its proficiency in designing and executing in vitro pharmacological assays and utilizing complex theoretical models for data analysis.

Binding & Signaling Kinetics:

• Binding rate constants (k_on/k_off)
• Covalent mechanism analyses, including two-step model and k_inact/K_i derived kinetic analyses
• Real-time quantification of second messenger signaling
• Integrate kinetics data to comprehend drug action over time

Mode of Action:

• Competitive and allosteric modulation of drug-target interactions
• Enzyme mechanisms and inhibition profiles
• Signaling pathway and ligand bias analysis
• These descriptors of drug action can be used to better predict clinical efficacy.

Targets

Excellerate has extensive experience working with a wide range of drug target families, including G protein-coupled receptors (GPCRs), kinases, nuclear receptors, enzymes and E3 ligases (targeted protein degradation).

• GPCRs: Signaling cascades (e.g. cAMP, β-arrestin, calcium)

• Kinases: Phosphorylation assays, allosteric & orthosteric binding

• Enzymes: Activity kinetics and substrate profiling

• Nuclear receptors: Hormone response pathways (e.g. nuclear translocation, transcriptional activity)

• Cytokines/growth factors: Immune modulation assessment, cytokine release assays, ELISAs

• E3 ligases/targeted degradation: Targeted protein degradation through ubiquitination assays, PROTAC profiling

• Subcellular organelle proteins: Subcellular localization (e.g. mitochondrial, lysosomal assays, organelle isolation)

• Protein-protein interactions

• Cell cycle/apoptosis/autophagy regulators

• Non-standard targets

Phenotypic Assays

Excellerate’s team of scientists are highly experienced in the development of in vitro assays report functional outcomes in relevant human cells.

Our reputation extends beyond target-directed pharmacology to dedicated expertise in human primary cell biology, and its application to target validation, screening and mechanism of action.

Phenotypic assays include, but are not limited to: proliferation, differentiation, apoptosis, viability, adhesion, migration, chemoattraction, phagocytosis, live imaging, cytokine release, knockout studies, flow cytometry analysis and cellular metabolism.

Broad panel phenotypic assays/systems covering:

• Cell health and metabolism

• Immunophenotyping

• Multiplex cytokine disease panels

• Complex models – 3D/spheroid, co-culture