Contract Research Organizations

Contract research organizations are companies that will perform specific in vitro and in vivo assays to testing the activity of compounds or therapies. Listed here are companies that the Shoichet lab has either worked with or considered working with in the past.

PDSP

The NIMH Psychoactive Drug Screening Program run by the Roth lab at UNC Chapel Hill, has been a close collaborator in performing in vitro binding and functional assays for almost all GPCR targets and and several transporters. If the PDSP has the assay, they are typically our first choice.

To submit compounds for screening:

1. Login to the PDSP.
2. Create a new request

• • Provide the grant number, name name, known activity and rational
  • Add the compounds and requested assays

Here is the address to send compounds vis FedEx (good as of 11/2014)

   PDSP
   Attn: Xi-Ping Huang
   120 Mason Farm Rd
   2113 Genetic Medicine Bldg
   Chapel Hill, NC 27514
   TEL: (919)-966-8777

When sending compounds provide:

• Shoichet Lab
• project name
• compound id, amount submitted, molecular weight (they usually would like at least 10 mg)
• label the vials with the ID/name and the PDSP# assigned (they will send you labels)

Eurofins Panlabs

Located in Taiwan, they have 1,350 assays covering the following target classes

• Cytokine/Chemokine (41)
• GPCR (270)
• Ion Channel (41)
• Kinase (154)
• Nuclear Receptor (16)
• Other (15)
• Phosphatase (31)
• Phosphodiesterase (19)
• Protease (51)
• Transporter (19)

They were used by both Henry Lin and Matthew O'Meara (2013-2014) and they gave reasonable results at reasonable prices.

The shoichet lab contact there has been (10/14):

   Judy Winslow, phone #: 425-785-3736, email: JudyWinslow@eurofins.com.

Reaction Biology

Located in Pennsylvania, Reaction Biology specializes in Kinase assays and have a few epigenetic and other assays:

• HMT/DNMT Assays
• HDAC/HAT Assays
• Bromodomain Assays
• DUB Assays
• Protease Assays
• PDE Assays
• CYP/hERG/Bcl/HSP90 Assays
• Cell Assays
• Phosphatase Assays

Their tag line is With the largest functional kinase activity assay panel in the industry, RBC provides kinase, epigenetic, and other profiling services to over 590 companies worldwide. RBC specializes in custom assay conditions, high quality reproducible data, and outstanding service.

• ~104.00USD for 10 dose IC50 singlet curve (with 20% academic discount)
• They have a minimum order of 300USD order

CarnaBio

Located in Japan, CarnBio has an extensive Kinase pannel of 311 targets and a 2-week turn around. Christian Laggner used them for the kinase assays in (Laggner NatChemBio 2012).

Multispan

In Hayward CA, Multispan 230 validated GPCR assays. 320 human GPCR and 180 murine GPCR cDNAs are cloned for custom assays. Apparently Mike Keiser has used them, though if PDSP has the target/assay that is the way to go.

ChanTest - Now part of Charles River

In Cleveland OH, they have a range of Ion Channel assays. Brian says we've used them before and they were reasonable. They've now been acquired by Charles River.

ChanTest has developed the world’s most complete library of validated human ion channel-expressing cell lines to serve all the ion channel needs of its pharmaceutical and biotech customers.

Aurora Biomed

Aurora’s product range includes automated liquid-handling equipment, atomic absorption spectrometers, atomic fluorescence spectrometers, ion channel screening technology and microwave digestion systems, increasing the efficiency of sample management in a wide range of research applications. We are headquartered in Vancouver, BC, Canada.

Matt worked with Andy Hegel (andrew.hegle@aurorabiomed.com) to test compounds with patch-clamp assays for the Systems SEA project in 2014. They gave us a discount of 200$ per datapoint.

PerkinElmer

AS OF JAN 1 2015 THEY ARE DISCONTINUING THEIR ASSAY SERVICES DIVISION

Large collection of in vitro services including:

• Cytochrome P450
• Cytokine/Chemokine Secretion
• GPCRs
• Ion Channels (Ligand- & Voltage-Gated)
• Kinases
• Nuclear Receptors
• Other - Enzymes
• Other - Receptors
• Phosphodiesterases (PDEs)
• Transporters

and some in vivo services

Complete Assay Services List

Optivia

Specialized in transporters, based in the Bay Area.

Solvo

Specialized in transporters, based in the Bay Area.

GenScript

They have few assays for different classes of targets

BPS Biosciences

Mostly enzymes

InvivoGen

Located in San Diego, focusing on immune response

Assays for Pattern Recognition Receptor activity

• Toll-Like Receptors
• NOD-Like Receptors
• RIG-I-Like Receptors
• C-type Lectin Receptors
• Cytosolic dsDNA Sensors
• Inflammasome
• Autophagy & Innate Immunity
• PRR & PAMPs Detection

INDIGO Biosciences

Located in Pennsylvania, they can do nuclear hormone assay.

Sora Labs

It looks like they have some enzyme assays that they can run.

FlouFarma

Located in France, high content screening of live cells

Cytoskeleton

Compound screening against tubulin, microtubule, myosin, sarcomere, kinesin and small G-proteins.

Cayman Chemical

• Assay Services

   Biochemists with experience in the areas of eicosanoids, steroids, oxidative stress, and inhibitor screening
   Use Cayman’s extensive line of well-characterized biochemical kits
   Enzyme immunoassay, colorimetric, and fluorometric assays available

• Screening Services

   Comprehensive screening laboratory focused on epigenetics
   Backed by our core strengths in protein production, assay development, chemical synthesis, and medicinal chemistry
   Capacity to test compounds at a rate of up to 100,000 compounds per week
   Ability to profile compounds against a broad epigenetic enzyme panel
   Includes assays for methyltransferases, demethylases, acetyltransferases, deacetylases (HDACs and SIRTS), and histone code readers (ex. bromodomain proteins)

DiscoveRx

GPCR, Kinases, Nuclear Receptors, Epigenetic Targets and Signaling Pathways

HD Biosciences

HD Biosciences Co., Ltd. is a Shanghai-based, biology-focused preclinical drug discovery contract research organization (CRO). They do hit identification, hit-to-lead, assay development in major target classes, such as GPCRs, kinases, ion channels and transporters, and in a high-throughput screening format using plate-based platforms. Our screening capabilities span from cell line generation, biochemical, and cell-based functional assays for receptors, enzymes and ion channels in a variety of techniques, including:

• Fluorescence (e.g. HTRF, FP, FRET, FLIPR, Flexstation)
• Absorbance
• Luminescence (e.g. luciferase, b-lactamase, deGFP, reporter gene)
• Radiometrics (e.g. SPA, MicroBeta, Filtration)
• Electrophysiology (e.g. patch clamps)
• ImageXpress (e.g. live cell image HCA/HCS)

Absorption Systems

Absorption Systems is a preclinical CRO. They have locations in Exton, PA, San Diego, CA, and Panama City, Panama. They work with a wide variety of customers in the pharmaceutical and biotech industry, including small virtual pharma companies, large pharma companies with weekly programs, and specialty CROs looking for services that complement their own offerings. In vitro and in vivo areas of speciality include:

• BCS + Biowaivers
• Wound healing and psoriasis disease models
• Formulation
• Metabolism
• Permeability
• Pharmacokinetics
• Protein binding (e.g. fraction bound in plasma)
• Toxicology
• Transporters

Cyprotex

Cyprotex is a contract research organization specializing in preclinical ADME-Tox with offices in the UK and US.

Permeability & Transporters

• Caco-2 permeability
• Transporter interactions
• PAMPA-GI and PAMPA-BBB
• MDCK and MDR1-MDCK
• Transdermal absorption
• Intranasal absorption

Distribution - reversible/time dependent

• Plasma protein binding
• Whole blood binding
• Blood to plasma ratio
• Brain tissue binding
• Microsomal binding

Metabolism

• Metabolic stability microsomes, hepatocytes, S9, plasma/blood
• Metabolite profiling and identification
• Reaction phenotyping
• CYP inhibition
• UGT inhibition
• MAO inhibition
• CYP induction
• PXR and AhR nuclear

receptor activation

• 3D microtissues

Brunswick Labs

Brunswick Laboratories is an independent, full-service bioanalytical laboratory specializing in the science of Antioxidants, Oxidative Stress, Anti-inflammatory, Synthetic and Natural Compound Bioanalysis.

   +1-508-281-6660
   blservices@brunswicklabs.com
   200 Turnpike Road, Southborough, MA 01772, USA

• Bioavailability, BioAbsorption, and BioUptake study via Caco-2 human intestinal cells
• Anti-inflammatory: LOX, COX, TNF-alpha, NFkB, Interleukins (ILs), and PGE2 as biomarkers
• Oxidative Stress Analysis for biological samples
• Antioxidation effect in a biological system: Nrf2, Cellular Antioxidant Assay (CAA)
• Diabetes and Weight Management: insulin secretion, insulin receptor activity, glucose uptake, glucose metabolism, and carbohydrate digestion as biomarkers
• Detoxification and Liver Function: Phase I and Phase II liver enzymes, liver function biomakers in serum
• Energy metabolism investigation via human cells
• Anti-cancer Function evaluation: cancer cell viability, proliferation, apoptosis, and invasion as biomarkers
• Anti-aging Assays: SIRT-1, telomerase activity as biomarkers
• Preclinical Investigations for Skin Care Products: UV protection, melanin (age spot) inhibition, anti-aging, anti-inflammatory

BioToxSciences

http://biotoxsciences.com/In_Vitro_Services

Based in San Diego, they have a range of in-vitro functional assays

Other CROs

• Ricerca
• Absorption Biosystems
• amsbio not really a CRO but apparently they can do assays
• ArrayBridge The have ~850 enzymes listed that they say they have assays for, but little detail on what services they actually provide.
• SB Drug Discovery 50 PDEs, 50 Ion Channels, NHRs, GPCRs, Inflammation
• DiscoverRX Kinase, Epigenetic, GPCR
• MetisLab Radioligand assays for GPCRs