Biotranex LLC

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
  

• Preclinical animals
  
• 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