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In Vivo
Pharmacology

Aragen has an experienced team of in vivo pharmacologists with strong domain knowledge in various animal models of disease to obtain in vivo proof-of-concept across multiple therapeutic areas. We have over 50 validated models in Oncology, Inflammation, Autoimmune Disease, Pain, Fibrosis, Cardiovascular and Metabolic Diseases. Disease biologists head each therapeutic area and compounds screened and characterized by our team have progressed to clinical studies. Our screening modalities include small molecules, large molecules and antibodies. We help our customers select appropriate disease models from our validated portfolio of models. This team has a proven track record in validating new disease models as required to meet the customized needs of various drug discovery programs. Our in vivo scientists are well aligned with industry requirements of quality, reproducibility of scientific data, and delivery timelines.

We follow acute, chronic, mechanistic and pharmacodynamic models to assess target engagement, efficacy, PK/PD correlation and biomarker evaluation, in collaboration with our in vitro pharmacology and DMPK teams. Our efficacy models are validated with appropriate standard of care compounds and supported by rigorous statistical analysis. Data generated from each in vivo study is confidential and accessible only to the client and study personnel. Password protected files can only be downloaded via email or restricted share points on Intralinks sites.

Vivarium

Aragen has over 40,000 sq ft of vivarium space distributed between locations in India (Hyderabad, Bengaluru) and the United States (Morgan Hill, CA). Rodents procured from globally reputed vendors such as Taconic Biosciences, Charles River Laboratories and The Jackson Laboratory support in vivo efficacy, pharmacokinetics and exploratory toxicology for clients. Our modern infrastructure includes individually ventilated caging, automated temperature and humidity control systems, and access control systems with round-the-clock monitoring by dedicated veterinarians and trained staff. We are AAALAC accredited, and all animal experiments are conducted in accordance with protocols approved by the Institutional Animal Ethics Committee (IAEC).

Certification
& Compliance
  • AAALAC and OLAW-accredited rodent vivarium facilities
  • 40,000 sq ft of total space across three discovery sites
  • In-house facility for rodent equipped IVC cages/conventional cages
  • Regulatory
    – OHSAS (Occupational Health and Safety Assessment Series) compliant
    – Institutional Animal Ethics Committee (IAEC) constituting external members and CPCSEA nominee
    – IAEC committee reviewed and approved protocols of study experimentation
    – Institutional Bio Safety Committee (IBSC) registered under Department of Biotechnology
    – Bio-waste Disposal Management registered under State Pollution Board
    – EMS (Environment Management System  as per ISO 14001)
    – Large animal (canine) PK studies with external collaborator
Quality
Systems
  • Procurement of animals from certified vendors (local subsidiaries of Taconic Biosciences, Charles River Laboratories and The Jackson Laboratory)
  • Documentation of animal health status at receipt
  • Subjecting all newly arrived animals to quarantine
  • Physical examination of animals by a veterinarian
  •  Clinical tests of animals:
    – Parasitological examination
    – Hematological
    – Biochemical
    – Microbiological examination of faeces for pathogenic organisms on blood agar
    – Feed, water and bedding material analysis
  • Dedicated veterinarians and pathologists to support efficacy and toxicity studies
  • Ethical efforts to avoid pain and distress to experimental animals
  • Anaesthesia and euthanasia as per CPCSEA guidelines

Clinical Pathology & Histopathology

Clinical pathology and histopathology routinely provide supporting validations for efficacy studies in Oncology, Inflammation, Pain, Toxicology, Cardiovascular and Metabolic Diseases. Our laboratories are managed by dedicated pathologists and veterinarians.

Oncology

Xenograft models of human cancer play an important role in the screening and evaluation of NCEs and NBEs as potential anticancer agents. Aragen scientists have developed and validated several xenograft models in Ncr Nu/Nu, NOD-SCID and SCID-Beige mice. We can customize and utilize any human cell line of interest to conduct in vivo proof-of concept studies for client NCEs and NBEs. Syngeneic models are tumor models whose genetic background is similar, if not identical to the host animal. As they retain an intact immune system, syngeneic models can be particularly pertinent for studies of immunologically-based targeted therapies that are either standalone or combinations. PK/PD correlations can be established by relating plasma and tumor exposure to tumor volume and weight, as well as to a panel of genomic, proteomic and metabolomic biomarkers.

Validated Xenograft/ Syngeneic Models
S.No.Cell LineCancer TypeOriginMice Used for Tumor Development
1A375MelanomaHumanNcr Nu/Nu Mice
2SK-OV-3OvarianHumanNcr Nu/Nu Mice
3KM-12ColonHumanNcr Nu/Nu Mice
4A549NSCLCHumanNcr Nu/Nu Mice
5MDA-MB-231BreastHumanSCID-Beige Mice
6DU-145ProstateHumanNcr Nu/Nu Mice
7PC-3ProstateHumanSCID-Beige Mice
8U87-MGGlioblastomaHumanSCID-Beige Mice
9A2780OvarianHumanSCID-Beige Mice
10MM1.SMultiple MyelomaHumanSCID-Beige Mice
11RPMI8226Multiple MyelomaHumanSCID-Beige Mice
12MV4-11Beta Myelomonocytic LeukemiaHumanSCID-Beige Mice
13B16F10MelanomaMiceC57BL/6 Mice
144T1BreastMiceBalb/c Mice
15A431SkinHumanNcr Nu/Nu Mice
16NCl-H460Large Cell Lung CarcinomaHumanNcr Nu/Nu Mice
17NCl-H358Non-small Cell Lung CancerHumanNOD-SCID Mice
18CT26.WTColon CarcinomaMiceBalb/c Mice
19Ba/F3A murine interleukin-3 dependent pro-B cell lineMiceNcr Nu/Nu Mice
20PLC/PRF/5HepatomaHumanNcr Nu/Nu Mice
21PANC-01Pancreatic CancerHumanSCID-Beige Mice
22AsPC-1Metastatic Pancreatic CancerHumanNcr Nu/Nu Mice

Other Oncology Support

  • 70+ cancer cell lines stored in-house to validate new models
  • Pharmacokinetics and bioavailability of various test materials in tumour bearing mice
  • Target engagement of compound in tumour tissue and PK/PD correlation
  • MTD studies in immunocompromised mice

Pain

Acute and chronic pain remain significant health problems despite tremendous progress in the understanding of their basic mechanisms. Studies conducted using intact animals allow the examination of the multidimensional nature of pain. Aragen scientists have developed various animal models to evaluate the efficacy of novel drug candidates against inflammatory, neuropathic and cancer pain.

Neuropathic Pain Models

  • Effect of tramadol on CCI (chronic constructive injury)-induced neuropathic pain in rats
  • Effect of gabapentin on SNL (spinal nerve ligation)-induced neuropathic pain in rats
  • Paclitaxel-induced polyneuropathic pain in rats
  • Streptozotocin-induced polyneuropathic pain in rats

Post-operative Pain Models

  • Brennan model of post-incisional pain in rats and mice

Inflammatory Pain Models

  • Complete Freund’s Adjuvant (CFA)-induced pain in rats
  • λ-carrageenan-induced pain in rats
  • MIA-induced osteoarthritis in rats

Inflammation

Inflammation is an early event that is the underlying cause of most diseases, including cancer. The inflammatory condition is associated with an activated immune system, including activated immune cells and biomolecules. Inflammatory models of diseases are therefore critical to the understanding of disease etiology across colitis, psoriasis, multiple sclerosis, arthritis and fibrosis. At Aragen, we employ animal models that show tissue-specific inflammation and utilize a variety of approaches, to evaluate novel treatments.

Inflammatory Fibrosis

  • Bleomycin-induced idiopathic pulmonary fibrosis (IPF) in mouse and rats
  • Carbon tetrachloride (CCl4)-induced liver fibrosis

Colon Inflammation

  • Dextran sodium sulphate (DSS)-induced colitis model

Dermal Inflammation

  • Imiquimod-induced psoriasis in mice
  • IL-23-induced psoriasis in mice
  • Oxazolone-induced ear/skin inflammation in mice

Multiple Sclerosis

  • MOG 35-55-induced experimental autoimmune encephalitis (EAE) in mice

Inflammatory Arthritis

  • Collagen-induced arthritis in DBA1J mice

Fibrosis

Fibrosis is an endpoint for multiple diseases and is driven by the excessive production and deposition of collagen and other extracellular matrix proteins in tissues and organs. The increase in tissue stiffness associated with fibrosis impacts the normal functioning of tissues such as the lung, kidney and liver. Our diet-induced, chemical-induced and surgical models of fibrosis, coupled with an extensive evaluation of disease biomarkers, as well as cellular and molecular mechanisms, can help drive research efforts towards finding novel therapies.

Liver Fibrosis

  • Streptozotocin (STZ)+high fat diet (HFD)-induced NASH
  • AMLN (Amylin Liver NASH) model in mice
  • Carbon tetrachloride (CCl4)-induced liver fibrosis

Lung Fibrosis

  • Bleomycin-induced idiopathic pulmonary fibrosis (IPF)

Kidney Fibrosis

  • Unilateral ureteral obstruction (UUO)

Cardiovascular & Metabolic Diseases

Cardiovascular and Metabolic Diseases, also known as lifestyle diseases, are the leading causes of morbidity and death in much of the modern world. The two major underlying causes are disorders of lipid metabolism, and metabolic syndrome that includes high blood pressure, high blood sugar, high fat and abnormal cholesterol. The ability to develop animal models that closely mimic the human disease condition is critical to advancing ameliorative or therapeutic treatments.

Obesity

  • Corn oil-induced dyslipidemia
  • Intralipid-induced dyslipidemia
  • Ghrelinemia model
  • Diet induced obesity (DIO)

Non-Alcoholic Steatohepatitis (NASH)

  • Streptozotocin (STZ)+high fat diet (HFD)-induced NASH
  • AMLN (Amylin Liver NASH) model in mice

Kidney Disease (CKD)

  • Adenine-induced CKD
  • Streptozotocin (STZ)+high fat diet (HFD)-induced diabetic nephropathy
  • Unilateral ureteral obstruction (UUO)

Cardiovascular Disease

  • Monocrotaline-induced pulmonary arterial hypertension (PAH)
  • Bleeding time model of hemostasis in rat

Learn more about our end-to-end capabilities