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CNS/Pain

WuXi CNS/Pain Discovery provides customer oriented integrated services with our AAALAC accredited animal facility and world class laboratories including GLP standard lab. We strive for highest data quality, consistency, and maximal efficiency.

Best-in-Class Capabilities

  • Functional leaders with disease and/or project leading experience
  • Technical leaders with extensive bench experience
  • Dedicated staff with a good training system
  • Western-pharma standard instrumentation and SOP
  • Multiple backups and new capacities expansion on-going
  • Functionally diversified and covered in GPCR, Kinase, Ion channels

In vitro and Ex vivo assays

  • In vitro assays
    • GPCRs
      • Receptor binding: radioligand competition (membrane or whole cell)
      • Function: cAMP, Calcium mobilization, IP1, beta-arrestin, reporter gene
      • Agonist, antagonist, and allosteric modulator
      • Receptor selectivity: binding, functional assays
      • MOA studies: binding mode; desensitization
    • Enzyme
      • Activity assay: kinases, proteases, and others
      • Kinase selectivity and panel screening
  • Ex vivo assays
    • Receptor binding
    • Native tissue membrane and primary neuronal culture
    • Cellular and biochemical readout: toxicity, survival
  • Biomarker/Biochemical assays: ELISA, WB, qPCR
  • Throughput: Hit-ID and SAR support

Electrophysiology

  • Current capacity
    • IonWorks Quattro: Using 384-well PatchPlates. Currently the machine is available for business. Daily capacity is about 3000 data points per day
    • QPatch systems: Two Qpatch machines can generate about 60 concentration-response curves per day. The machine is half loaded now
    • Manual patch-clamp for culture cell recording: Four rigs in place, current capacity is about 10 concentration-responses per day
    • Brain slice recording: One rig is available, about 2-6 cells per day
    • GLP hERG: One qualified rig. One compound per day
  • Ion channel targets expansion
    • Stable cell lines:
      HERG-HEK
      Kv10.1-CHO
      P2RX7-CHO
      TRPV1-HEK
      Nav1.4-CHO
      Nav1.6-CHO
      Nav1.7-CHO
    • Final constructs:
      Nav1.8
      nAChR
      7-Ric3
      Stim1/Orai1
      Stim1/Orai3
      Kir3.1-3.4
      TRPV4

In vivo pharmacology & translational science

Due to the importance of translation science in CNS/pain drug discover, we aim to set up the capability to help the success of clinical phase II. So far, we have developed rat MIA model measured with weight-bearing which is considered as the most relevant animal model for Osteoarthritis. Receptor occupancy method was also developed to provide target engagement evidence.

Besides translation science, we have built broad spectrum of animal models for CNS diseases and chronic pain to provide systematical in vivo drug discovery and development service with multiple endpoints including: behavior, efficacy, PK/PD, safety, biomarkers assay, and pathology.

Translational models of CNS/Pain

  • Monosodium Iodoacetate (MIA)
  • In vivo brain receptor occupancy measurement

Pain models & measurements

  • Acute nociception
    • Tail flick
    • Hot plate
  • Acute inflammatory pain
    • Formalin
    • Capsaicin induced tactile allodynia
    • Carrageenan
  • Chronic inflammatory pain
    • CFA
  • Chronic neuropathic pain
    • SNL: spinal nerve ligation (Chung)
    • CCI: chronic constriction injury
    • PNL: partial nerve ligation
    • Diabetic/chemotherapy pain
  • Post surgical pain
    • Brennan model in rats
  • Visceral pain
    • Acetic acid writhing in mice
  • Itching model
    • Compound 48/80 induced Itching model in mice

CNS models & measurements

  • Safety assays
    • Irwin test
    • FOB (functional observational battery)
    • Spontaneous locomotor activity
    • Rotarod test
    • Grip strength
  • Cognitive function assays
    • Morris water maze
    • Passive avoidance
    • Delayed alternation task (Y-maze)
    • Novel object recognition (NOR)
    • Attentional set shifting
  • Schizophrenia
    • Prepulse inhibition of startle (PPI)
    • Conditioned avoidance response (CAR)
    • PCP or Amephtamine induced hyperlocomotor activity
    • SubPCP or NeoPCP induced cognitive deficits
  • Anxiety and depression
    • Vogel conflict test
    • Open field
    • Elevated plus maze
    • Forced swimming test
    • Learned helplessness
  • Parkinson’s Disease (PD)
    • HIC (haloperidol induced catalepsy
    • 6-OHDA unilateral lesion model
    • Akinesia model in 6-OHDA PD rats
    • L-DOPA induced dyskinesia in 6-OHDA PD rats
  • Alzheimer’s Disease (AD)
    • Scopolamine induced amnesia models