Biotranex LLC

• Preclinical animals

MDR3cyte™ Inhibition Assay

MDR3cyte™ is a patent-pending assay that is the only physiologically relevant assay available to assess test agent inhibition of human multidrug resistance protein 3 (MDR3). MDR3cyte™ is a hepatocyte-based platform that measures test agent inhibition of MDR3, provides cross-species studies, and offers the ability to investigate the effect of in situ drug metabolism on inhibition; the assay is run without radioactive reagents.

MDR3cyte™ employs a 96-well plate format with liquid chromatography-mass spectrometry quantification. The assay is accurate, reproducible, sensitive, and possesses a wide dynamic range. MDR3cyte™ was developed to be cost competitive and high-throughput.

MDR3cyte™ shows excellent correlation with drugs that cause human drug-induced liver injury (DILI) and MDR3 inhibition. MDR3cyte™ is your assay to test MDR3 inhibition and minimize the risk of unexpected DILI.

BSEPcyte® Hepatocyte-Based BSEP Inhibition Assay

BSEPcyte™ is a patented assay (United States patent number 9,772,325) that offers significant advantages over bile salt export pump (BSEP) assays that use membrane vesicle preparations. BSEPcyte™ is a physiologically relevant hepatocyte-based platform that measures test agent inhibition of BSEP or Bsep, provides cross-species comparisons, and offers the ability to investigate the effect of in situ drug metabolism on inhibition; the assay is run without radioactive reagents.

BSEPcyte™ employs a 96-well plate format with liquid chromatography-mass spectrometry quantification. The assay is accurate, reproducible, sensitive, and possesses a wide dynamic range. BSEPcyte™ was developed to be cost competitive and high-throughput.

BSEPcyte™ shows excellent correlation with drugs that cause human drug-induced liver injury (DILI) and BSEP inhibition. BSEPcyte™ is your assay to test BSEP inhibition and minimize the risk of unexpected DILI.

Biotranex provides laboratory services for pharmacokinetics/metabolism/chemical toxicology studies including:

• Animal pharmacokinetics
• Bioanalysis
• Drug Metabolism
• Drug Transporters
• Metabolite profiling
• Structural identification of metabolites
• Metabolic soft-spot identification
• Reaction phenotyping studies for CYP, UGT, SULT, aldehyde oxidase and hydrolytic enzymes, and determination of Km and Vmax
• Elucidation of metabolic pathways
• Mechanistic drug development studies such as addressing metabolism-based toxicity issues
• Metabolite identification and semi-quantitation in plasma samples of humans and animal species
• Preparation of metabolite standards
• Identification of reactive metabolites: GSH adduct, DNA adduct, covalent binding, protein adduct
• Hepatoxicity using human or animal hepatocytes

• LC-MS/MS structural identification, metabolic profiles, and species comparisons.
• NMR structure elucidation
• Radioactive or non-radioactive materials

Biotranex provides a full range of services to study drug absorption and transporter properties to meet the FDA and EMA Guidance:

• BSEPcyte(R) inhibition Assay
• MDR3cyte(R) inhibition Assay
• Bilirubincyte(R) inhibition Assay
• Absorptive and bidirectional permeability in MDCK or Caco-2 monolayers
• PAMPA permeability
• Mono- or bidirectional permeability determination in P-gp- and BCRP-transfected cell lines
• Transporter phenotyping/inhibition (IC50 or Ki): efflux P-gp, BCRP and BSEP; uptake OATP1B1, OATP2B1, OATP1B3, OAT1, OAT3, OCT1, OCT2
• Hepatic uptake in hepatocytes from human and animals

Biotranex offers services to scale up metabolite production using bioreactors and chemical synthesis:

• Glucuronide metabolites, oxidative metabolites
• Milligram and gram quantities for structural elucidation and activity testing
• Animal tissue fractions and cell lines
• Fungal and bacterial strains for metabolite formation

• Screening for CYP inhibition
• Regulatory required CYP inhibition
• Mechanism CYP inhibition
• Metabolism dependent CYP inhibition

• Microsomes
• Hepatocytes
• S9
• Cytosol
• Expressed enzymes
• Slow metabolism

• PAMPA assay
• MDCK and Caco-2 permeability
• Pgp and BCRP transfected cell lines

• BSEPcyte(R) inhibition Assay
• MDR3cyte(R) inhibition Assay
• Bilirubincyte(R) inhibition Assay
• Hepatocyte cytotoxicity
• CYP induction
• Metabolic stability
• Metabolic profiling

• CYP activity
• mRNA
• Primary hepatocytes - human and animal

• Human
• Animal

• Primary hepatocytes
• BSEPcyte(R)
• MDR3cyte(R)
• Bilirubincyte(R)
• Reactive intermediates
• Cell lines

• Cell lines (over 20 cell lines available)
• Primary hepatocytes
• BSEPcyte(R)
• MDR3cyte(R)
• Bilirubincyte(R)
• Reactive intermediates

• Transporter phenotyping/inhibition (IC50 or Ki): uptake OATP1B1, OATP2B1, OATP1B3, OAT1, OAT3, OCT1, OCT2
• Hepatic uptake in hepatocytes from human and animals

• Plasma protein binding (cross species)
• Tissue protein binding
• Tissue concentration (parent and metabolites)
• Blood/plasma partition
• Covalent binding

• Over 20 cell lines

Biotranex offers integrated drug discovery services including:

• DMPK: comprehensive package
• Pharmaceutics: solubility and permeability
• Toxicology: cytotoxicity, hERG, Ames, chemical toxicity, telemetry

Biotranex provides consulting services for IND and NDA filings:

• Conduct necessary studies to meet regulatory requirements
• Help to formulate an IND/NDA filing strategy
• Prepare reports and the regulatory filing documents
• Serve as the subject matter expert

Clinical Research Services

Pharmacology Services