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AfaSci, Inc.

Redwood City, California, US

AfaSci, Inc. is San Francisco Bay Area based biotech company committed to enhancing health care by conducting research and development in Biotechnology and Therapeutics.

Our team began with designing, producing and marketing an in vivo drug screening platform: SmartCageTM. This system enables automated, medium throughput assessment of drug effects on rodent neurobehavior as well as assessments in a variety of disease models. By leveraging our proprietary research platform, AfaSci’s scientists have been discovering investigational new drug (IND) candidates targeting ion channels and GPCRs in the CNS therapeutic area, focusing on neuropathic pain, epilepsy and Alzheimer’s disease. The lab is NIH OLAW certified.

Recent Publications

  • Akihiko Ozawa, Gloria Brunori, Daniela Mercatelli, Jinhua Wu, Andrea Cippitelli, Bende Zou, Xinmin (Simon) Xie, Melissa Williams, Nurulain T. Zaveri, Sarah Low, Gre´gory... Show more »

AfaSci, Inc. is San Francisco Bay Area based biotech company committed to enhancing health care by conducting research and development in Biotechnology and Therapeutics.

Our team began with designing, producing and marketing an in vivo drug screening platform: SmartCageTM. This system enables automated, medium throughput assessment of drug effects on rodent neurobehavior as well as assessments in a variety of disease models. By leveraging our proprietary research platform, AfaSci’s scientists have been discovering investigational new drug (IND) candidates targeting ion channels and GPCRs in the CNS therapeutic area, focusing on neuropathic pain, epilepsy and Alzheimer’s disease. The lab is NIH OLAW certified.

Recent Publications

  • Akihiko Ozawa, Gloria Brunori, Daniela Mercatelli, Jinhua Wu, Andrea Cippitelli, Bende Zou, Xinmin (Simon) Xie, Melissa Williams, Nurulain T. Zaveri, Sarah Low, Gre´gory Scherrer, Brigitte L. Kieffer, and XLawrence Toll1 Knock-In Mice with NOP-eGFP Receptors Identify Receptor Cellular and Regional Localization. The Journal of Neuroscience, August 2015
  • Jianyu Lu a, Angelo Aguilar a, Bende Zou b, Weier Bao a, Serkan Koldas a, Aibin Shi a, John Desper a, Philine Wangemann c, Xinmin Simon Xie b, Duy H. Hua Chemical synthesis of tetracyclic terpenes and evaluation of antagonistic activity on endothelin-A receptors and voltage-gated calcium channels Bioorganic & Medicinal Chemistry, June 2015
  • Andrea Cippitelli, Jinhua Wu, Kelly A Gaiolini, Daniela Mercatelli, Jennifer Schoch, Michelle Gorman, Alejandra Ramirez, Roberto Ciccocioppo, Taline V Khroyan, Dennis Yasuda, Nurulain T Zaveri, Conrado Pascual, Xinmin (Simon) Xie and Lawrence Toll. AT-1001: a high-affinity α3β4 nAChR ligand with novel nicotine-suppressive pharmacology British Journal of Pharmacology, November 2014
  • Mario A. Saporta a,b,⁎, Vu Dangb, Dmitri Volfsonb, Bende Zou c, Xinmin (Simon) Xie c, Adijat Adebola d, Ronald K. Liem d, Michael Shy a, John T. Dimos b Axonal Charcot–Marie–Tooth disease patient-derived motor neurons demonstrate disease-specific phenotypes including abnormal electrophysiological properties Experimental Neurology, October 2014
  • Narendiran Rajasekaran1, Ricky Tran, Conrado Pascua, Xinmin Xie, Elizabeth D. Mellins Reduced Locomotor Activity Correlates with Increased Severity of Arthritis in a Mouse Model of Antibody-Induced Arthritis Journal of Rheumatology and Autoimmune Diseases, 2014
  • Sarah Srodulski, Savita Sharma, Adam B Bachstetter, Jennifer M Brelsfoard, Conrado Pascual,Xinmin Simon Xie, Kathryn E Saatman, Linda J Van Eldik and Florin Despa Neuroinflammation and neurologic deficits in diabetes linked to brain accumulation of amylin Molecular Neurodegeneration, 2014
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AfaSci, Inc. has not listed any services.

Neuropathic Pain Animal Models
Price on request

Neuropathic pain models:

  • Chemotherapy-induced neuropathy
  • Streptozotocin (STZ)-induced diabetic neuropathy
  • Antibody-induced Arthritis (Mice)
  • Spinal Nerve Ligation
  • Spared nerve injury (SNI) of the sciatic nerves (Rats & Mice)
  • Tibial Neuroma Transposition (TNT) Model (Rats)

Neuropathic pain models:

  • Chemotherapy-induced neuropathy
  • Streptozotocin (STZ)-induced diabetic neuropathy
  • Antibody-induced Arthritis (Mice)
  • Spinal Nerve Ligation
  • Spared nerve injury (SNI) of the sciatic nerves (Rats & Mice)
  • Tibial Neuroma Transposition (TNT) Model (Rats)
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Mouse
Rat
hERG Channel Inhibition Assay
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hERG Safety Tests Using Patch-Clamp Recordings (Patch Clamp hERG Testing)

Introduction
A fatal ventricular tachyarrhythmia called Torsade de Pointes (TdP)1 can occur in many patients with inherited long QT syndrome (LQTS) who have defects in the expression/functionality of a unique human cardiac K channel encoded by... Show more »

hERG Safety Tests Using Patch-Clamp Recordings (Patch Clamp hERG Testing)

Introduction
A fatal ventricular tachyarrhythmia called Torsade de Pointes (TdP)1 can occur in many patients with inherited long QT syndrome (LQTS) who have defects in the expression/functionality of a unique human cardiac K channel encoded by the human ether-a-go-go-related gene (hERG)2. Some drugs also induced LQTS resulting from hERG channel blockade. A number of noncardiovascular drugs have either been withdrawn from the market, or failed in clinical trials due to their propensity to inhibit hERG leading to prolong the QT interval of the cardiac electrocardiogram (ECG) and subsequently cause a potentially TdP. Therefore, hERG test as earlier as possible is critical step to early screen out potentially cardiac toxicity compounds. Since hERG is a voltage-gated ion channel, manual whole-cell patch voltage-clamp recording is the gold-standard technique.

AfaSci offers hERG test
AfaSci specialized in electrophysiology and will provide contract services using standard manual patch clamp recordings of hERG channels in mammalian cells.
Initial Screening hits a single concentration screen, n = 2 per compound
Characterizing leads multiple concentrations-response studies in a cumulated manner (typically 4 concentrations), n = 2 – 3 per concentration

High quality and rapid turnover using manual patch-clamp recordings and complete study in 1 week per compound.

Cell culture
The hERG-expressing CHO cell line grows rapidly in EX-CELL 302 Media (Sigma), supplemented with 10% fetal bovine serum, 4mM L-Glutamine, 1% Penicillin-Streptomycin, and 250 μg/mL G-418 (Geneticin) as the selection agent.

Patch-clamp recording
Whole-cell voltage-clamp electrophysiology will be employed to test compounds and always with positive control compound, e.g., cisapride. Extracellular solution contains (in mM): NaCl (130), KCl (5), CaCl2 (1), Glucose (10), HEPES-Na (10) (pH 7.4 adjusted with HCl). Internal pipette solution contains (in mM): KF (120), CaCl2 (1), MgCl2 (1), KCl (10), EGTA (11), HEPES (10), KOH (11) (pH 7.2 adjusted with KOH). The hERG potassium currents will be recorded using Axon 700B amplifier under a holding potential of -80 mV and then depolarized to 40 mV for 2.5 seconds to activate the hERG channel. The hERG tail current is induced by a repolarizing pulse to -50mV for 4 seconds. The amplitude of the tail currents is recorded in the absence and presence of drugs. A 250 millisecond prepulse to -50mV is applied for leak subtraction. This voltage-clamp pulse protocol is performed continuously during the experiment every 20 seconds allowing recovery from inactivation.

Test protocol
Initial screening at a single concentration based on 30-fold of therapeutic target potency, n = 2-3
IC50 determination to be determined on those compounds passed initial screening. Typically 4 – 5 concentrations will be tested and each concentration is applied for 2 min to reach a steady-state inhibitory level prior to the next higher concentrations tested. Each concentration is tested at 2 – 3 times (n = 2 - 3). Cisapride and vehicle will be tested in each study for positive and negative controls.

References
1. Haverkamp, W., G. Breithardt, et al. The potential for QT prolongation and proarrhythmia by non-antiarrythmic drugs: Clinical and regulatory implications. Report on a policy conference of the European Society of Cardiology. Eur Heart J, 21:1216–1231, 2000.
2. Sanguinetti, M.C., C. Jiang, et al. A mechanistic link between an inherited and an acquired cardiac arrhythmia: hERG encodes the IKr potassium channel. Cell, 81:299–307, 1995.

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Animal Electromyography
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EEG-EMG recordings Electroencephalograph (EEG) and electromyograph (EMG) monitoring is the gold standard technology for monitoring sleep and brain seizures. Currently sleep is not routinely measured in animals subject to various drug treatments, disease models, or genetic alteration partly due to the difficulty associated with the... Show more »

EEG-EMG recordings Electroencephalograph (EEG) and electromyograph (EMG) monitoring is the gold standard technology for monitoring sleep and brain seizures. Currently sleep is not routinely measured in animals subject to various drug treatments, disease models, or genetic alteration partly due to the difficulty associated with the use of EEG and EMG. EEG recording of wakeful activity, sleep and abnormal brain electrophysiology (e.g., seizures) are detailed in our publications.

Model Assay Name Measurements
EEG/EMG recordings 1. Electric activity of the brain 1. Wake
2. Electric activity of the muscle 2. REM (Rapid eye movement sleep)
3. NREM (slow wave sleep)
4. Abnormal activity (e.g.,seizures)
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Electroencephalogram (EEG) Models
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EEG-EMG recordings Electroencephalograph (EEG) and electromyograph (EMG) monitoring is the gold standard technology for monitoring sleep and brain seizures. Currently sleep is not routinely measured in animals subject to various drug treatments, disease models, or genetic alteration partly due to the difficulty associated with the... Show more »

EEG-EMG recordings Electroencephalograph (EEG) and electromyograph (EMG) monitoring is the gold standard technology for monitoring sleep and brain seizures. Currently sleep is not routinely measured in animals subject to various drug treatments, disease models, or genetic alteration partly due to the difficulty associated with the use of EEG and EMG. EEG recording of wakeful activity, sleep and abnormal brain electrophysiology (e.g., seizures) are detailed in our publications.

Model Assay Name Measurements
EEG/EMG recordings 1. Electric activity of the brain 1. Wake
2. Electric activity of the muscle 2. REM (Rapid eye movement sleep)
3. NREM (slow wave sleep)
4. Abnormal activity (e.g.,seizures)
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Microelectrode Array (MEA) Recordings
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Extracellular Recording
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Stroke Animal Models
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Model Assay Name Measurements
Middle cerebral artery occlusion (MCAO) 1. SmartCage monitoring Assay 1. Locomotion, active/inactive rhythm
2. Neurologic score Assay 2. Neurological score
3. Behavioral tests Assay 3. Behavior
Model Assay Name Measurements
Middle cerebral artery occlusion (MCAO) 1. SmartCage monitoring Assay 1. Locomotion, active/inactive rhythm
2. Neurologic score Assay 2. Neurological score
3. Behavioral tests Assay 3. Behavior
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Epilepsy & Seizure Animal Models
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Mode Assay Measurement
1. Chemical (e.g., metrazol)-induced seizures 1. Seizure-induction test 1. Seizure-induction latency
2. Electrical-induced seizures (maximal or minimal electrical shock) 2. Anti-epileptic test 2. Seizure number
3. Seizure duration
4. Seizure-induced fatality
Mode Assay Measurement
1. Chemical (e.g., metrazol)-induced seizures 1. Seizure-induction test 1. Seizure-induction latency
2. Electrical-induced seizures (maximal or minimal electrical shock) 2. Anti-epileptic test 2. Seizure number
3. Seizure duration
4. Seizure-induced fatality
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Sleep Disorder Animal Models
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Model Assay Measurements
1.Wild type mice 1. EEG/EMG Assay 1. Brain neuronal and muscle activity activity
2.Transgenic mice 2. Noninvasive sleep (using floor vibration sensor) Assay 2. Respiration as slow sleep biomark
3.Control
4.Treatment
Model Assay Measurements
1.Wild type mice 1. EEG/EMG Assay 1. Brain neuronal and muscle activity activity
2.Transgenic mice 2. Noninvasive sleep (using floor vibration sensor) Assay 2. Respiration as slow sleep biomark
3.Control
4.Treatment
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Animal Fear Conditioning Studies
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Tone- and contextual-conditioning fear

Tone- and contextual-conditioning fear

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Animal Social Behavior Tests
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Novel Object Recognition Test
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Barnes Maze Test
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Morris Water Maze Assay
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Custom Pain Animal Models
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Model Assay Measurements
1. Spared nerve injury-induced neuropathic pain 1. Hargreaves (focus, local hot pain test) Assays 1 and 2: Thermal pain thresholds – hyperalgesia
2. Streptozotocin (STZ)-induced diabetic neuropathy 2. Hot plate (broader pain test); cold pain Assays 3... Show more »
Model Assay Measurements
1. Spared nerve injury-induced neuropathic pain 1. Hargreaves (focus, local hot pain test) Assays 1 and 2: Thermal pain thresholds – hyperalgesia
2. Streptozotocin (STZ)-induced diabetic neuropathy 2. Hot plate (broader pain test); cold pain Assays 3 and 4: Mechanical pain thresholds - allodynia
3. Chemotherapy (e.g. taxol)-induced neuropathy 3. von Frey hair test Assays 5: Measure weight bearing balance - allodynia
4. Reserpine-induced chronic pain accompanied with depression 4. UGO analgesia meter Assays 6: Measure both acute nociceptive pain (early phase) and central sensitization pain (later phase)
5. UVB radiation-induced neuroinflammatory pain 5. Incapacitance tester
6. Electrocutaneous stimulation-induced facial pain 6. Automated magnetic detection of paw licking, raising or shaking
7. Dental inflammatory pain
8. Incision-induced neuroinflammatory pain
9. CFA-induced neuroinflammatory pain
10. Formalin-induced inflammatory pain
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Animal Social Interaction in Pairs Test
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Rodents
Sucrose Preference Test
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Rat
Forced Swim Test
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Mouse
Rat
Tail Suspension Test
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Mouse
Patch Clamp Recording
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Ion Channel Screening Assays
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Animal Learning, Memory, and Behavior Tests
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Animal Model in vivo Analyses
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In vitro Ion Channel Assays
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CNS/Neurology Animal Models
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Animal Anxiety and Depression Tests
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In vitro Cardiotoxicity Screening
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Animal Cognition & Behavior Tests
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Electrophysiology
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Animal Models of Disease
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Pharmacology & Toxicology
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Biology
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Pain/Neuropathy Animal Models
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Cell-Based Assays
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Animal Models and Studies
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Project and Process Management
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Small Animal MEG
Small Animal Magnetoencephalography
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Small Animal Functional Brain Imaging
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Animal Electroencephalography (EEG)
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Toxicology
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Toxicology Services

Toxicology Services

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