Murigenics

• Syngeneic Tumor Cell Line Models:
  
  • CT26, MC38, SA1N, LLC, 4T1, A20, Panc02, B16F10
    
• Human Tumor Cell Line Model: (many more not included)
  
  • Prostate: PC3, DU145, LNCaP, 22Rv1
    
  • Breast: BT474, MCF7, SKBR3, BT 483
    
  • Colorectal: HT29, SNU C2B, HCT-116
    
  • Lung: NCI H460, A549, NCI-H2
    
  • Melanoma: WM115, A375
    
  • Ovarian: SK-OV3. OvCAR3
    
  • Pancreatic: BxPC3
    
  • Glioblastoma: A172
    
• Hematopoietic Tumors:
  
  • MV-4-11, K562, MMI.S
    

Determining the pharmacokinetics (PK) of novel test compounds is essential for approximating efficacy during the drug development and discovery phases. At MuriGenics, we provide a wide-range of murine pharmacokinetic, bioavailability and biodistribution services that can be customized to meet the needs of our clients.

In order to screen for possible gene-compound interactions, MuriGenics provides preclinical pharmacogenetic PK profiling through the use of a variety of strains of rats or mice. In addition, a PK component can be added to a Disease Model study to assess changes within PK parameters during a particular disease state.

As with all of our in vivo services, we guarantee continued communication during on-going studies and will contact you directly with any questions or concerns. This helps to guarantee that any data collected is both biologically and clinically reliable and relevant.

Species

• Mice (outbred, inbred, genetically engineered strains, contact us for additional information on a specific strain or with questions regarding strains that may express a specific phenotype of interest)
  
• Rats (implanted catheters available, inquire about strains)
  

PK Dose Administration

A compound of interest is delivered via one of several routes. Typically, there are 3-5 animals/dose/group. Some studies may require several concentrations of a particular compound of interest or the use of different formulations and vehicles. Routes of administration available for drug delivery include:

• Oral
  
• Intravenous
  
• Intramuscular
  
• Intraperitoneal
  
• Subcutaneous
  
• Topical
  
• Intratracheal
  
• Slow Infusion
  
• Continuous Infusions (Osmotic or syringe pump)
  

Sampling Time Points

At various time points set forth in the study protocol, blood samples (tissue samples) will be collected and processed. The number of and distance between time points will be dependent upon the compound, the route of administration, and its half-life.

Biliary Pharmacokinetics

Biliary pharmacokinetic studies may be conducted to determine biliary excretion and clearance of test articles.

PK Analysis in Disease Models

Since the pharmacokinetics of a compound may change during disease influencing efficacy, PK studies may be performed in conjunction with Disease Models. Contact us to inquire about adding a PK component to one of our available disease models or to discuss a study idea of your own.

Cell-based assay development can range from cytotoxic assays, such as apoptosis, to cell proliferation, calcium mobilization, and cell-based immunoassays. Mechanisms of action, including receptor binding, receptor activation, cell signaling, drug internalization and subcellular localization can be delineated in cell-based assays following treatment with your pharmaceuticals.

If the standard animal models or cell-based assays don’t meet your needs, Murigenics will help you develop new models and experimental protocols to suit.

Bioassay development encompasses testing of conditioned medium, cell lysates or whole cells in a variety of formats these include ELISA and Luminex immunoassays along with immunohistochemical methods such as flow cytometry.

Additionly, MuriGenics has GxP capabilities through the use of the FlexStation3 system, a multiplatform, high-throughput instrument. This platform has a wide range of applications for cell and bioassays.

• Cell-Based Assays
  
• Immunoassays
  
• Additional Capabilities and Instrumentation

MuriGenics performs a variety of in vitro toxicity screens and assays. Performing in vitro cytotoxicity assays prior to animal testing may be a cheaper alternative for initial drug screens. Since many of these tests require cell-based assays, our experience in cell biology, enables us to analyze cells using molecular and biochemical techniques as well as morphologically.

In Vitro Myelotoxicity

Myelotoxicity is a serious side-effect of many chemotherapeutic and immune-suppressive agents. This condition can lead to serious life-threatening infection and neutropenic sepsis. MuriGenics provides a panel of screens designed to help our clients gain insight into the likelihood and degree to which their compounds may produce myelotoxicity and thus aid them in lead candidate selection. Below is our panel of screens:

• CFU-GM (Colony Forming Unit Granulocyte Monocyte) for Neutropenia
  
• CFU-GEMM (Colony Forming Unit Granulocyte Erythrocyte, Monocyte Megakaryocyte) for Multipotential Cytopenias
  
• BFU-e (Busrt Forming Unit Erythroid for Erythropenia)
  
• CFU-Mk (Colony Forming Unit Megakaryocyte) for Thrombocytopenia
  
• Cytometry
  
• Hematopoietic Assays
  
  • Long Term Cultures (LTCIC) Assays
    
  • Characterization of Hematopoietic Cells
    

In Vitro Hepatotoxicity – Rat

Drug-induced hepatic injury is a common reason for the withdrawal of an approved drug. Drug-induced hepatotoxicity ranges from asymptomatic elevation of liver enzymes to fulminant hepatic failure. We perform a series of assay screens that may be utilized throughout the discovery and development phases in conjunction with traditional in vivo methods to aid the client in the selection of a lead compound. Below is a list of assessments that we perform:

• Morphological Evaluation
  
• LDH Leakage
  
• MTS
  
• Pathology Specific Hepatotoxicity
  
  • Steatosis
    
  • Phospholipidosis
    
• CYP Inhibition/Induction (Drug/Drug Interactions)
  
  • bDNA – Luminex xMAP Platform
    
  • ATPase Assay (Transporters)

Allotransplantation

• Skin Transplantation – Host Immune Response to Foreign Tissue (Murine Allograft)
  

Airpouch

• Lipopolysaccharide (LPS)
  
• Carrageenan
  

Contact Hypersensitivity & Delayed-Type Hypersensitivity

• Dermal 2,4-Dinitro-1-Fluorobenzene (DNFB)
  
• Intradermal Methylated-BSA
  

Dermal

• Dermal Scar Model
  
• Skin Inflammation
  

Hepatitis

• Non-Lethal LPS/D-GalN Induced Hepatitis (Acute Model)
  

Inflammatory Bowel Disease (IBD)

• Dextran Sodium Sulfate in Drinking Water (DSS)
  
• Colonic Instillation of Trinitrobenzene Sulfonic Acid (TNBD)
  

Local Inflammation

• Carrageenan Injection Hind Paw
  
• Passive Cutaneous Analphylaxis (PCA)
  

Peritonitis

• Thioglycollate, Mineral Oil, or Pristane-Induced
  

Pulmonary Inflammation (Lung Injury)

• Lipopolysaccharide (LPS)
  
• Ovalbumin (OVA)
  

Renal Acute Inflammation

• Unilateral Ureter Obstruction (UUO)
  
• High-Protein Diet (rats)
  

Sepsis

• Intraperitoneal Lipopolysaccharide (LPS)
  
• Intraperitoneal Staphlococcal Enterotoxin-B (SEB)

Obesity, Diabetes and Metabolic Syndrome

• Dietary
  
  • C57BL/6J or /6N Mouse Diet-Induced Obesity (DIO)
    
  • Fructose Diet Sprague Dawley Rat
    
• Genetically Modified
  
  • db/db
    
  • ob/ob
    
  • Zucker Fatty Diabetic Rat (ZDF)
    
  • Zucker Fatty Rat
    

Renal Failure

• Goto-Kakizaki (GK) Rats Treated with a High-Salt Diet & Angiotensin II
  

Steatosis

• Atherogenic Diet (Piagen)
  
• C57BL/6J High-Fat Diet
  
• ob/ob; db/db
  
• NON/ShiLtJ High-Fat Diet
  
• Dietary Methionine/Choline Deficient

• Neutropenic Thigh Model (Cyclophosphamide and IM Bacteria Injection)
  
• Superficial Skin Wound Infection Model

• Intestinal Transit Time of Alimentary Bolus
  
• Biliary Secretion by Cannulated Bile Duct (see also Pharmacokinetics)
  
• Gastric Emptying of Liquids and Solids

• Parkinson’s Disease by MPTP Injection (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine)
  
• Behavioral
  
  • Elevated Plus-Maze
    
  • Open Field Activity
    
  • Tail Suspension
    
  • Startle Response
    
  • Hang Time

• Atherosclerosis: Transgenic and Atherogenic Diet
  
  • ApoE -/-
    
  • LDLR-/-
    
  • sPLA2-trangenic
    
• Carotid Artery Ligation (mouse)
  
• Hypertension
  
  • Spontaneously Hypertensive Rat (SHR) Model
    
  • Angiotensin-2 Infusion
    
  • High-Salt Diet
    
• Restenosis Following Carotid Balloon Angioplasty (rat)
  
• Chemically-Induced Carotid Thrombus Formation (rat)
  
• Thrombosis
  
  • Tail Bleeding Time
    
  • Blood Coagulation Time

• Collagen Induced Arthritis (CIA)
  
• Type-2 Collagen Monoclonal Antibody (mAB) Cocktail

• MOG (myelin-oligodendrocyte-glycoprotein) Induced
  
• PLP (proteolipid protein) Induced
  
• Passive Transfer of Sensitized Lymphoid Cells

Non-Obese Diabetic (NOD Mice)

Drug Discovery & Development Services

Cytotoxicity Assays Services