Capability
Axcelead offer a comprehensive set of best-in-class capabilities to meet a range of customer needs.
Screening
Hit finding
| Planning of hit identification strategy | Target assessment | |
| Design of screening cascade | ||
| Proposal of compound library | ||
| Assay development for screening | Material preparation (cDNAs, proteins, cells) | |
| Assay development (Enzymes, GPCRs, transporters, ion channels, nuclear receptors, etc.) | Biochemical assay | |
| Biophysical assay | ||
| Phenotypic assay (Cell line, Primary cells, iPS cells) | ||
| Protein-protein interaction; PPI | ||
| Electrophysiological assay | ||
| High throughput screen (HTS)* *Various read-outs including also radiometric formats *Ability to perform HTS under BSL2 conditions | Assay adaptation for HTS (full automation, miniaturization) | |
| Pilot screen (HTS assay validation) | ||
| HTS campaign and Data analysis | Primary screening | |
| Counter screening |
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| EC50/IC50 measurement | ||
| Purity test | ||
| Hit follow up (Hit expansion, species difference, selectivity, mechanism of action, etc.) |
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Lead generation/optimization
| in vitro evaluation of compounds for hit/lead/IND generation |
| in vitro profiling and MOA/kinetics analysis |
| Biochemical analysis |
| Biophysical analysis（SPR, ASMS, TSA, ITC, NMR） |
| Structural biology for SBDD and FBDD |
| Cell-based assay |
Compound library management
| Compound logistics | Compound storage (Vials, tubes; 96&384 tube, Plates; 96&384&1536 well) |
| Compound quality control | |
| Powder weighing | |
| Liquid handling and reformatting | |
| Compound information management | |
| Managing, recording and reporting of all manipulation of client samples | |
| Library management(Consulting services) | |
| Facilities and Equipment | Lab-automation system |
| Fully automated storage systems | |
| Compound Logistics IT system (managing, recording and reporting of all operations of client samples) |
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Chemistry
Medicinal Chemistry
| “All-in-One” Medicinal Chemistry services, from hit compound identification to selection of IND candidate compounds |
| Design and synthesis of new compounds for broad ranges of target diseases and target classes |
| Consultation |
Peptide chemistry
| Candidate-oriented research on lead peptide creation and optimization |
| Peptide synthetic |
| Consultation |
Synthetic chemistry
| Development of practical synthetic routes |
| Non-GLP API synthesis (up to 1 kg) |
| Synthesis of internal standards |
| Synthesis of labeled compounds |
| Synthesis and identification of estimated metabolites |
| Platform technology |
| High-temperature and/or high-pressure reaction using autoclaves |
| Micronization by jet-milling |
High-throughput synthesis
| High-throughput parallel synthesis |
| Reaction screening |
Analytical chemistry
| NMR structural analysis |
| Quantitative NMR |
| Fragment screening (ligand-based protein NMR) |
| X-ray diffraction analysis |
| HPLC analysis and purification |
Computational chemistry
| Computer-aided drug discovery (SBDD/LBDD/FBDD) |
| Molecular design through molecular dynamic simulations |
| Virtual screening |
| Design of screening library |
Biology
Pharmacology studies in oncology
In vitro studies
| Cancer cell proliferation assays | Cell panel |
| 3D cultures (spheroid culture, soft agar culture) | |
| Combination effect analysis | |
| Cancer immunology-related analysis | T cell cytotoxicity assay |
| Target validation, Mechanism of action analysis, biomarker analysis | |
in vivo studies
| Antitumor efficacy studies | |
| Pharmacology studies by IVIS | |
| Target engagement, pharmacokinetic/pharmacodynamic (PK/PD) analysis: blood, tumor, mouse organs | |
| Tumor-infiltrating lymphocyte (TIL) analysis | |
| Immunodeficient mouse model (xenograft model) | Human cancer cell lines / patient-derived tumor (PDx) |
| Subcutaneous tumor, orthotopic tumor, metastasis, systemic dissemination models | |
| Immunocompetent mouse model (syngeneic model) | Mouse cancer cell lines |
| Subcutaneous tumor, metastasis models | |
Pharmacology studies in immunological disorders
in vitro studies
| Analyses of cytokine production, signal activation, and cell types in primary culture cells and whole blood |
| Proliferation assays of T cells, B cells, etc. |
| Th1, Th17, and Treg differentiation assays |
| Migration and apoptosis assays of splenocytes, thymocytes, B cells, neutrophiles, etc. |
| Target validation, Mechanism of action analysis, Biomarker analysis |
in vivo studies
| Target engagement and PK/PD analysis: Cytokine production and intracellular signal activation, etc. | |
| Immune cell phenotyping in blood, lymph nodes, and various other tissues (Flow cytometry using 5-laser BD LSRFortessaTM) | |
| Antibody production assay | |
| Animal models | Models of inflammatory bowel diseases |
| Multiple sclerosis model | |
| Rheumatoid arthritis model | |
| Psoriasis models, etc. | |
Pharmacology studies in central nervous system diseases
in vitro studies
| Protein and gene expression analysis in primary central nervous system cells |
in vivo studies
| Behavioral test(Psychiatric-disease-related) | Prepulse inhibition test |
| 3-chamber sociability test | |
| Psychostimulant-induced hyperactivity |
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| Behavioral test(Motor function) | Grip strength test |
| Rotarod | |
| Running wheel test | |
| Behavioral test(Cognitive function) | Novel object recognition test |
| 8-Arm radial maze test | |
| Target engagement and PK/PD analysis | Microdialysis |
| Sleep EEG | |
| Pathological analysis | |
| Collection of cerebrospinal fluid (CSF) | |
| Animal models | Cognitive dysfunction models (scopolamine, MK-801) |
| Valproic acid-induced autism model | |
| Poly (I:C) model of schizophrenia | |
| Development of animal models by intracerebral injection |
Pharmacology studies in cardiovascular diseases
in vitro studies
| Hypertrophy, apoptosis, and cell signaling assay in primary cardiomyocyte |
| Isolated perfused rat heart (Langendorff perfused heart) |
| Aortic ring preparation |
| Target validation, Mechanism of action analysis, Biomarker analysis |
in vivo studies
| Target engagement and PK/PD analysis | ||
| CV safety (blood pressure, cardiac function, and electro-cardiogram, etc.) | ||
| Animal models | Ischemia/reperfusion model | |
| Heart failure models | Heart failure models (Small animals): MI model, TAC model etc. | |
| Heart failure models (Large animals)：Ischemia/reperfusion Heart failure models, MI model | ||
| Cardiac function measurement by cardiac catheterization | ||
| Cardiac function measurement by echocardiography | ||
| Hypertension models | ||
| Pulmonary hypertension model | ||
| Renal disease models (Alport syndrome mouse etc.) | ||
Pharmacology studies in metabolic diseases
in vitro studies
| Fibrosis evaluation in co-culture of hepatic stellate cell and hepatocyte |
| MOA analysis of lowering/increasing blood glucose, body weight loss/gain |
| Glucose metabolism / lipid metabolism assay in primary hepatocyte, cell lines of hepatocyte, pancreatic β cell, and adipocyte |
| Lipid metabolism assay in isolated skeletal muscle |
| Target validation, Mechanism of action analysis, Biomarker analysis |
in vivo studies
| Target engagement and PK/PD analysis | ||
| Animal models | Non-alcoholic steatohepatitis (NASH) models(MC4R-KO mice fed western diet、Choline-deficient high-fat fed mice、Drug-induced fibrosis model etc.) | |
| Diabetes models(Small animals） | Glucose tolerance test | |
| insulin tolerance test | ||
| Glucose clamp technique | ||
| Diabetes models (Large animals) | ||
| Obesity models | Body composition analysis (Echo-MRI and X-ray CT) | |
| Energy expenditure analysis (Open-circuit indirect calorimeter) | ||
Pharmacology studies in gastrointestinal motility disorders
in vitro studies
| Magnus test |
in vivo studies
| Defecation studies |
| Bead expulsion assay |
| Colonic manometry test |
Pharmacology studies for cell therapy using large animals
in vivo studies
| Immunosuppressed models | Immunosuppressed porcine model | |
| Immunosuppressed monkey model | Cell engraftment evaluation | |
| Disease models | Heart failure porcine/monkey model Type 1 diabetes porcine model |
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Omics
| Metabolomics | Pathway analysis |
| Analytical method development for target metabolites | |
| Lipidomics | Non-target analysis covering over 20 lipid classes |
| Proteomics | Protein turnover analysis |
| Protein-protein interaction analysis | |
| Phospho-proteomics | |
| Post-translational modification profiling |
Bioinformatics
| Data analysis | MoA analysis using global omics data |
| Annotations (gene functions, mutation, etc.) | |
| Data visualization | |
| GWAS | |
| Gene mutation analysis | |
| Single-cell RNA-seq data analysis | |
| Biomarker discovery | |
| Transcriptomics | Ampli-seq |
| Genomics | Target re-sequencing |
| 16S rRNA sequencing for microbiome analysis | |
| Consultation on omics data acquisition and validation study plan | |
Genetically modified animals (mice)
| Generation of knock-out (KO) rodents |
| Generation of transgenic (Tg) rodents |
| Generation of knock-in (KI) rodents |
| Creation of humanized rodents |
| Additional gene modification to rodent disease models |
| Cleaning to SPF grade and breeding(Rodents introduction from outside organizations) |
| Cryopreservation of embryos and sperm of rodents |
| gRNA design and vector construction for genome |
DMPK
ADME Screening
| ADME Screening | Purity |
| Kinetic solubility | |
| log D | |
| PAMPA | |
| MDR1 substrate screening (using NIH MDR1-MDCK cell) | |
| Metabolic stability | |
| CYP inhibition | |
| CYP3A time-dependent inhibition (TDI) | |
| CYP induction | |
| Plasma protein binding | |
| Cassette dosing (rodents) |
Discovery DMPK Studies
| Bioanalysis (including method development) | |
| In vitro studies | CYP phenotyping studies |
| CYP3A time-dependent inhibition (TDI) | |
| CYP induction | |
| Non-CYP metabolism studies | |
| Hepatocyte metabolic clearance | |
| Metabolite structural analysis (in vitro/in vivo) | |
| Blood/plasma concentration ratio | |
| Substrate specificity studies using various transporter-expressing cells | |
| Inhibition studies using various transporter-expressing cells | |
| Plasma protein binding | |
| Skin permeability studies | |
| GSH/CN trapping studies | |
| Pharmacokinetic studies in various animal species | Cassette dosing (non-rodents) |
| Tissue distribution, urinary/biliary excretion | |
| Parenteral administration (transdermal, intranasal, pulmonary, sublingual, intrarectal, etc.) | |
| Compound optimization / translational research | Structure-property relationship |
| DDI risk assessment | |
| Human PK, effective concentrations, and effective doses prediction | |
| PK/PD/E analysis, TK/TD analysis, modelling & simulation (Business partnership with Leiden Advanced PK/PD) https://lapp.nl/ | |
Physicochemistry and Preformulation Studies
| Physicochemical property profiling | Purity |
| Crystal form / crystallinity | |
| Thermal property | |
| Hygroscopicity | |
| Particle size | |
| Thermodynamic solubility, etc. | |
| Development form selection | |
| Formulation for animal experiments | |
| Stability (solid, solution, dosing formulation) | |
Pre-clinical development
| Consulting on development strategy and individual issues |
| Design of customized nonclinical data package for IND/NDA |
| Evaluation of the risk of drug-drug interaction at early development stage |
| Development of entire strategy for metabolites |
| Modeling & simulation from nonclinical to clinical stages in cooperation with LAP&P |
Safety
In vitro Exploratory Safety Studies
| Cytotoxicity | Glu/Gal cytotoxicity assay(HepG2 cell) |
| Phospholipidosis | Phospholipidosis assay(HepG2 cell) |
| Cardiotoxicity （ QT/Proarrhythmic potential assessment ） | hERG, Nav1.5 peak, Cav1.2 automated patch clamp |
| Microelectrode array(MEA)assay(hiPS-cardiomyocytes) | |
| Off-target | Receptor binding/enzyme assay |
| Genotoxicity | umu microtest(TA1535/pSK1002) |
| Ames test(TA100, TA98) | |
| Micro-Ames test(TA100, TA98) | |
| In vitro micronucleus test(TK6 cell) | |
| Multi-Flow DNA damage assay(γH2AX/pHH3/p53/polyploidy(TK6 cell)) |
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| Phototoxicity | UV/Vis absorption spectra |
| In vitro 3T3 NRU phototoxicity test |
In vivo Exploratory Safety Studies
| TK/tolerability studies in rodents and non-rodents | |
| Preliminary range-finding repeated-dose toxicity studies (including TK studies) | TK/tolerability studies |
| Cardiovascular safety pharmacology study (including TK studies; possible in conscious or anesthetized condition) | rodents |
| non-rodents | |
| Preliminary embryo-fetal development toxicity study in rodents and rabbits (including TK studies) | |
| In vivo photo toxicity studies in rodents | |
| Improvement of oral absorption for insoluble drugs due to nanoparticle preparation technology | |
| In vivo micronucleus tests in rodents | |
IND/NDA enabling
In vivo definitive safety studies for investigational new drug (IND) application*
| Repeated-dose toxicity studies in rodents and non-rodents |
| Safety pharmacology studies |
| Genotoxicity studies |
*: GLP-compliant (including partly subcontract)
In vivo definitive safety studies for new drug application (NDA)*
| Reproductive and developmental toxicity studies |
| Long-term Repeated-dose toxicity studies |
| Carcinogenicity studies |
| Juvenile animal toxicity studies in rodents |
*: GLP-compliant (including partly subcontract)
Toxicity mechanism studies / Target validation / Efficacy Studies
| Preliminary toxicity evaluation in pharmacology studies |
| Characterization of disease models and Tg/KO animals |
| Neuro-electrophysiological examinations due to compound muscle action potentials (CMAPs) or motor evoked potentials (MEPs) in rodents |
| Pharmacology studies of regenerative medicines in immunosuppressed animals |
| Ocular function evaluation and mechanistic studies of ocular toxicity (ex. quantitative determination of cataract, ERG, cornea histological examination in life and cotton yarn/Schirmer tear test in rodent) |
| Histology services (Special staining, immunohistochemistry, and in situ hybridization) |
| Whole slide image analysis / Morphometry (Fibrosis, G-ratio, etc.) |
| Electron microscopic examinations |
| Clinical pathology (Hematology, Blood chemistry, Blood coagulation test, Blood compatibility test, Hemolysis test, Urinalysis) |
| Exploratory tumorigenesis studies for development of regenerative medicine products |
| Exploratory carcinogenicity/tumorigenicity studies of regenerative medicines in immunodeficient mice |
| Laser capture microdissection |
Consulting services
| Non-clinical safety consultation in various developmental phases (screening phase, candidate nomination, candidate selection, IND, NDA) |
| Consultation on issues inquired from the regulatory authorities |