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Drug Discovery at BioDuro (Icon)

Pharmacology

Comprehensive studies that elucidate pharmacodynamics, mechanism of action, and efficacy of candidate compounds. In vivo and in vitro studies are conducted with utmost care and compliance with best industry practice.

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Overview

BioDuro’s pharmacology team has extensive drug discovery and development experience in the pharmaceutical industry enabling us to support fully integrated programs, including study design and data interpretation. Special expertise in metabolic and inflammatory diseases is coupled with a commitment to working with clients to develop customized models for rare diseases. By working together closely, our chemists, discovery biologists, and drug metabolism and pharmacokinetics (DMPK) scientists are able to provide BioDuro clients a range of flexible service models including integrated programs, full time employee (FTE) services or fee-for-services (FFS).

BioDuro Advantage

  • Scientific staff with a broad range of educational backgrounds
  • Dedicated, collaborative project management
  • Versatility in animal handling, dosing and surgery
  • Integrated discovery programs

Services

  • Translational research
  • Biomarker discovery & development
  • Compound efficacy validation
  • Consultation

Capabilities (Therapeutic focus)

  • CNS
    • Mouse/rat BBB
    • Formalin-induced nociceptive response (Pain) model
  • Metabolic Disease
    • Compound efficacy validation
      • Glucose homeostasis
      • Energy homeostasis
      • Grip strength and coordination
    • Metabolic diseases animal models
      • High fat diet induced obese (DIO) rats/mice
      • Streptozotocin (STZ) induced type 1 diabetic rats/mice
      • High fat diet (HFD) + STZ induced type 2 diabetic rats/mice
      • KKAy mice with NASH, retinopathy, nephropathy
      • ob/ob and db/db mice
      • GK (Goto-Kakizaki ) rats
      • ApoE KO mice
      • Myocardial infarction and reperfusion injury in rats/mice
      • Renal ischemia and reperfusion injury in rats/mice
    • In Vivo Assays
      • Oral/intraperitoneal glucose, insulin and pyruvate tolerance tests
      • Glucagon challenge tests
      • Hyperinsulinemic-euglycemia clamp
      • Hyperglycemia clamp
      • Energy expenditure indirect calorimetry system (TSE)
      • Infrared locomotor activity monitoring
      • Food intake and water intake monitoring
      • Urine and feces collection
      • Treadmill exercise
      • Body composition analysis (MRI)
      • Grip strength
      • Coordination (Rotarod)
 

NASH

NASH Model

BioDuro’s pharmacology team has developed highly clinically translatable animal NASH model to evaluate drug candidates. With short NASH induction periods of 6 weeks in mice and 8 – 12 weeks in hamsters our NASH models successfully mimics the pathogenesis of clinical NASH patients and exhibits hallmarks of NASH, including steatosis, lobular inflammation, ballooning and fibrosis within 20 weeks of dieting.

BioDuro Advantage

  • Clinical Relevance
    • Obesogenic NASH models featuring all the major indicators of NAFLD to moderate NASH, including dyslipidemia, inflammation, ballooning and robust fibrosis.
    • Pharmacologic responses
      • Reference compounds (OCA, Elafibrinor, Semaglutide) in our high fat diet + modified high fat diet (HFD+mHFD
      • NASH mouse model matches the responses of these experimental drugs in clinical trials
    • Histology and biomarkers
      • Demonstrate clinically relevant levels of disease phenotype & scores.
      • Includes steatosis, ballooning, inflammation, mallory body and fibrosis
    • Metabolic profiles
      • Similarly altered obesity markers as does human NASH, including insulin, glucose, cholesterol, triglycerides and free fatty acid.
    • Mechanisms of action
      • Drugs targeting diverse biological pathways and processes
  • Speed
    • High fat diet + modified high fat diet (HFD + mHFD) mouse model with shorter induction period between 12 – 16 weeks
    • High fat, high cholesterol + Fructose (HFC+F) hamster models with induction period between 8 – 12 weeks
  • Comprehensive
    • 5 different NASH disease models
    • Multiple induction methods:
      • Obesogenic (HFD, mHFD, AMLN)
      • Chemical induction (AMLN+CCL4)
      • Nutrient deficient (MCD)
  • Collaborative & Comprehensive
    • Group leaders & study directors provide rapid feedbacks and consultations to your preclinical model studies, including model selection, study design and data interpretation

Services
NAFLD/NASH Models & in Vitro Assays

  • Nutrient-deficient NASH Models
    • SD rat or C57bl mice fed on MCD diet for 1-2 weeks
    • SD rat or C57bl mice fed on 0.1MCD diet for 2-6 weeks
  • Chemically induced NASH Models
    • AMLN/HFD + CCl4 in C57bl mice, 12+4 weeks
    • Featured with inflammation, steatohepatitis and fibrosis
  • Obesogenic dietary NASH Models
    • HFD + modified HFD/WD in C57bl mice, 16 weeks
  • Genetic NASH Models
    • ob/ob mice with AMLN diet, 8-12 weeks
  • Hamster NASH Model
    • Golden Syrian hamsters
    • High fat & high cholesterol (HFC) plus fructose, 8-12 weeks
  • Fatty Liver
    • Liver weight
    • Liver Function: ALT, AST
    • Lipid panel (liver & serum): TC, TG, FFA
    • Insulin resistance : Insulin, BG
    • Histology: HE
  • Hepatic Fibrosis
    • Collagen type 1a, 3a, α-1 Procollagen
    • SMA-a, TGF-b
    • Hydroxyproline
    • Histology Sirius Red staining
  • Hepatic Inflammation
    • TNF-a levels
    • Mononuclear cell infiltration
    • Oxidative Stress:
      • Reactive oxygen species
      • Hydroxynonenal (HNE) levels

NASH Models Induced with Modified HFD Plus Fructose

  • Models which exhibit hallmarks of NASH
    • Modified High Fat Diet plus Fructose induces hepatosteatosis and fibrosis with increased
      • Insulin
      • Glucose
      • Cholesterol
      • Triglyceride
      • FFA
    • Histopathology: increased steatosis, ballooning, inflammation, Mallory body and Fibrosis
    • The phenotype is consistent to human metabolic syndrome/NASH-Fibrosis
  • The positive control drug showed significant effects after 8 weeks treatment:
    • Reduced liver enzymes
    • Reduced Cholesterol
    • Lowered BW
    • Reduced Liver TG
    • Lowered the NAS score and fibrosis percentage
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