Browse Our Catalog - In Vitro ADMET Laboratories

In Vitro ADMET
Laboratories, LLC
In Vitro ADMET Laboratories
Services & Products
1
Dear Colleague:
IVAL is proud to offer products and contract services that represent more than three decades of expertise in the application
of in vitro experimental systems to evaluate drug metabolism,
drug-drug interactions and drug toxicity. Our flagship products:
High-quality plateable cryopreserved human and animal hepatocytes and associated cultured media. We are proud to offer a
broad variety of human and animal cryopreserved hepatocytes
that can be used either in short-term (as suspensions) or longterm (plateable) cultures. Our pooled plateable cryopreserved
human hepatocyte product minimizes individual variations for
studies requiring lengthy incubations that cannot be performed
with hepatocyte suspensions.
We continue to expand our contract service offerings to supplement our customers’ in-house
capabilities. In addition to the more routine in vitro ADMET studies such as metabolic stability,
P450 inhibition and P450 induction, we now offer gene expression analysis for ADMET-related
genes for laboratories unable to run RT-PCR analysis in-house. Other pertinent contract services include a novel human hepatocyte hepatotoxicity screening assay that we co-developed
with the US FDA National Center for Toxicological Research (NCTR). The assay has been validated with over 150 DILI and non-DILI drugs.
We continue to develop innovative approaches and high throughput screening assays to aid the
selection of best drug candidates for early phases of drug development. These assays include
in vitro screening for hepatotoxicity, non-hepatic toxicity using primary cells from non-hepatic
organs, CYP3A4 inhibition screening, and CYP3A4 induction screening assays.
Our IdMOC® assay for co-culturing of cells from multiple organs is gaining acceptance worldwide. With IdMOC®, we expand our toxicity research capabilities. We now offer single cell
type organ-specific toxicity assays using primary cultured cells from target organs, as well as
IdMOC® co-cultures of these cells to allow multiple organ interactions. IdMOC® represents a
practical cell culture system to evaluate the role of hepatic metabolism on non-hepatic toxicity.
We strive to be the best in our field: best products, best service, and best hepatocyte technologies. Your feedback and suggestions are important to us - please feel free to contact me
at: [email protected].
With my best regards,
Albert P. Li, PhD, MBA
President and CEO
In Vitro ADMET Laboratories, LLC
2
About IVAL
In Vitro ADMET Laboratories, LLC (IVAL) was founded in 2004 by Dr. Albert P. Li. The company’s core competencies are based on Dr. Li’s experience in drug metabolism, toxicology, and what has become his lifetime
commitment to improving the quality, availability and understanding of hepatocytes for drug development
research.
IVAL’s scientists deliver invited seminars, conduct scientific courses, provide hands-on workshops and collaborate on drug development initiatives with a wide variety of organizations worldwide, including academic,
pharmaceutical, biotech, and government agencies.
Our company takes a collaborative and educational approach toward helping our customers get the best
results from their research and continues to innovate ways to prepare, preserve and use hepatocytes for more
consistent and reliable results from one of the most widely used in vitro test systems in drug metabolism and
toxicity research. So whether you seek high-quality hepatocytes, contract service resources, or education
focused on new technologies and in vitro hepatocyte practices, IVAL is the Complete Hepatocyte Solutions™
company.
In Vitro ADMET Laboratories, LLC
9221 Rumsey Road, Suite 8
Columbia, MD 21045
Tel: 410-869-9037
Toll-free: 866-458-1094
Fax: 410-869-9034
Email: [email protected]
In Vitro ADMET Laboratories, LLC
Boston Hepatocyte Technology Center
389 Main Street, Suite 301 - 304
Malden, MA 02148
Tel: 781-397-9300
Fax: 781-397-9309
Email: [email protected]
In Vitro ADMET
Laboratories, LLC
CompleteHepatocyteSolutionsTM
3
Contents
Products
Hepatocytes
Fresh suspensions and plates
Standard Fresh Hepatocyte Products
Cryopreserved hepatocytes
Human
Pooled Human Cryopreserved Hepatocytes, Plateable Grade
Pooled Human Cryopreserved Hepatocytes, Suspension Grade
Individual donors
Animal
Plateable and Suspension Grade
OnDemand Pre-plated Cryopreserved Hepatocytes
Genetically-Engineered Mouse (GEM) Hepatocytes
mRNA Primers
Media & Media Kits
IVAL Cryopreserved Hepatocyte Characterization Kit (I-CHCK)
Media
Plates and Cell Culture Vessels
CellAffix®
IdMOC® plates
Services
ADME
Metabolite Profiling / Species Comparison
Metabolic Pathway Identification (Reaction Phenotyping)
Metabolic Stability
Metabolism of Low-clearance Compounds (relay assay)
DDI
P450 Induction
P450 Inhibition
Gene Expression Assay
Toxicity
Metabolism-dependent Toxicity (Utility of IdMOC®)
Primary Cell Cytotoxicity Assay
HTS / screening services
HTS CYP3A4 Assays: Inhibition, Time-Dependent Inhibition, and Induction
sDILI (384-well plate study) ROS/ATP
Multiple Organ Toxicity Screening
Organ-specific Toxicity Screening
Anti-cancer Drug Screening
Adverse Drug Effects (ADE) High-throughput Screening
Training and Education
Hepatocyte Workshops
Symposia
4
In Vitro ADMET Laboratories, LLC
Copyright 2014
Products
Hepatocytes
Hepatocytes are used for an ever-increasing
number of research applications, yielding
important data on drug safety early in the drug
development process. Since they are an intact
cellular system, they contain the major hepatic
drug-metabolizing enzymes as well as the cofactors required to study the four categories
of xenobiotic biotransformation: hydrolysis,
reduction, oxidation and conjugation. They also
provide useful information regarding potential
toxicity and transporter activity of drug candidates.
Using high-quality hepatocytes with the right
media formulation can make a significant difference in the reliability of your test system
performance and data confidence. With over
30 years of hepatocyte and media development
experience, our dedication to provide the highest quality hepatocytes and support products is
unsurpassed.
Recommended Uses
Metabolism
P450 Induction
P450 Inhibition
Time-Dependent Inhibition
Transporters
Toxicity
Metabolism-Dependent
Toxicity
Metabolic Stability
Metabolite Profiling
Fresh
Suspensions
Short-term
X
X
Uptake only
X
X
Plated
Long-term
X
X
X
Uptake and efflux
X
X
X
X
Cryopreserved
Suspensions
Plateable
Short-term
Long-term
X
X
X
X
X
Uptake only Uptake and efflux
X
X
X
X
X
X
IVAL • www.invitroadmet.com • 1-410-869-9037 or 1-866-458-1094 • Email [email protected]
5
Hepatocytes: Fresh Suspensions and Plates
IVAL routinely prepares and ships fresh hepatocytes in both suspension and plated formats, using
our proprietary hepatocyte media to assure optimal performance. Animal hepatocytes are prepared
according to our posted schedule, found at www.invitroadmet.com, and custom preparations can be
arranged when you need them. Availability of human hepatocytes is contingent on tissue receipt,
which will be announced to our Hep-arrIVAL contact list.
Suspensions are sold per million cells (minimum: 10 million), or can be plated to suit your use in a
variety of well formats, with or without overlay.
Standard Fresh Hepatocyte Products
Species
Human
Monkey, Cynomolgus
Dog, Beagle
Rat, Sprague-Dawley
Mouse, CD-1
6
Individual / Pooled
Suspension
Individual
Individual
Individual
Pooled
Pooled
X
X
X
X
X
Multiwell Plates
(6 to 96-well format)
X
X
X
X
X
IVAL • www.invitroadmet.com • 1-410-869-9037 or 1-866-458-1094 • Email [email protected]
Products
Fresh Hepatocyte Catalog Numbers
(xx = well format (06, 12, 24, 48, 96)
Species
Human
Monkey
Dog
Rat
Mouse
Catalog
Number
86001
86001-XX
86001-XXM
86005
86005-XX
86005-XXM
86004
86004-XX
86004-XXM
82020
86003-XX
86003-XXM
82022
86002-XX
86002-XXM
Description
Human hepatocytes, male or female , fresh suspension
Human hepatocytes, male or female, fresh, no overlay
Human hepatocytes, male or female, fresh, overlay
Cynomolgus Monkey hepatocytes, male or female, fresh suspension
Cynomolgus Monkey hepatocytes, male or female, fresh, no overlay
Cynomolgus Monkey hepatocytes, male or female, fresh, overlay
Beagle Dog hepatocytes, male or female, fresh suspension
Beagle Dog hepatocytes, male or female, fresh, no overlay
Beagle Dog hepatocytes, male or female, fresh, overlay
SD Rat hepatocytes, male or female, fresh suspension
SD Rat hepatocytes, male or female, fresh, no overlay
SD Rat hepatocytes, male or female, fresh, overlay
CD-1 Mouse hepatocytes, male or female, fresh suspension
CD-1 Mouse hepatocytes, male or female, fresh, no overlay
CD-1 Mouse hepatocytes, male or female, fresh, overlay
IVAL • www.invitroadmet.com • 1-410-869-9037 or 1-866-458-1094 • Email [email protected]
7
Cryopreserved Hepatocytes
Cryopreserved hepatocytes are conveniently stored and available
in large lots for long-term projects and historical data consistency.
These products are also extensively characterized aiding the selection
of the best test system for each intended use. Their utility is welldocumented for evaluating a variety of compound properties including
interaction of drug transporters (efflux and uptake), enzyme induction
(P450 and transporters), enzyme inhibition (P450 and transporters),
drug metabolism, and hepatotoxicity. Our plateable hepatocytes are
of the highest quality, forming stable, near 100% confluent cultures
that can also be used in any multi-well format (including IdMOC®) to
evaluate metabolism-dependent toxicity.
IVAL’s understanding of hepatocytes as an in vitro test system is
unmatched. By subjecting our cryopreserved hepatocytes to a wide
Cryopreserved Human
variety of characterization assays and using them in our contract
Hepatocytes, 5 days after plating
services and scientific collaborations, we get to know our products
and their performance capabilities at the individual lot level. We work
with our customers to recommend the in vitro test system best suited to yield optimal results from
their planned experiments.
Our standard selection of products (shown below) offers species from toxicologically relevant
animal models and human, available in a wide selection of lots for both suspension and plateable
applications.
IVAL’s Standard Hepatocyte Products
SPECIES
HUMAN
MONKEY, CYNOMOLGUS
MONKEY, RHESUS
MONKEY, AFRICAN GREEN
BABOON
DOG, BEAGLE
RAT, SPRAGUE-DAWLEY
RAT, WISTAR
MOUSE, CD-1
MOUSE, C57B6
8
POOLED
X
X
X
X
X
X
INDIVIDUAL
DONOR
X
X
X
X
X
X
SUSPENSION
X
X
X
X
X
X
X
X
X
X
PLATEABLEINDUCIBLE
X
X
X
IVAL • www.invitroadmet.com • 1-410-869-9037 or 1-866-458-1094 • Email [email protected]
X
X
X
X
X
Products
Cryopreserved Hepatocytes: Human
Pooled Human Cryopreserved Hepatocytes, Plateable Grade
Pooling hepatocytes from several donors mitigates the issues associated with unique
individual donor profiles and limited quantities, approximating an average human
response in vitro.
•
•
•
•
•
•
Multiple donors, mixed gender
Plateable, Inducible
Large lots
P450 and Phase II activities
More than 5 million cells per vial
Viability greater than 80%
Fold Induction Comparison
Individual Re-cryopreserved Lots
versus
Re-cryopreserved Pool of the same lots
45
40
Fold Induction (mRNA)
IVAL’s new QuickReFreeze™ pooling process not only
preserves many of the attributes of primary cells, it
also minimizes waste during production and optimizes
viability to provide you with the best cryopreserved
human pools available.
35
30
25
20
15
10
5
0
Omeprazole 50μM
CATALOG
NUMBER
82003
82004
82005
Phenobarbital 1000μM
Rifampin 20μM
DESCRIPTION
Pooled cryopreserved human hepatocytes, male, plateable grade
Pooled cryopreserved human hepatocytes, female, plateable grade
Pooled cryopreserved human hepatocytes, mixed gender, plateable grade
Recommended media for Pooled Plateable Human Cryopreserved Hepatocytes:
Thawing:
Universal Cryopreserved Recovery Medium (UCRM™)
50 mL: Catalog Number 81015
Plating:
Universal Primary Cell Plating Medium (UPCM™)
50 mL: Catalog Number 81016
500 mL: Catalog Number 81017
Incubation:
Hepatocyte Induction Medium (HIM™) with supplements
50 mL: Catalog Number 81018
500 mL: Catalog Number 81019
Media Kit:
I-CHCK: IVAL Cryopreserved Hepatocyte Characterization Kit
(Human and Monkey): Catalog number 85002
IVAL • www.invitroadmet.com • 1-410-869-9037 or 1-866-458-1094 • Email [email protected]
9
Pooled Human Cryopreserved Hepatocytes, Suspension Grade
Pooled cryopreserved human hepatocytes are the preferred in vitro test system for
drug metabolism, inhibition and uptake transporter assessments. Pooling hepatocytes from several donors mitigates the issues associated with unique individual
donor profiles and limited quantities, approximating an average human response in
vitro.
IVAL’s new QuickReFreeze™ pooling process minimizes waste during production and optimizes viability to provide you with one of the best cryopreserved human pools available.
•
•
•
•
•
Multiple donors, mixed gender
Suitable for suspension incubations
Characterized for P450 and Phase II activities
More than 5 million cells per vial
Viability greater than 80%
CATALOG
NUMBER
82032
82033
82034
DESCRIPTION
Pooled cryopreserved human hepatocytes, male, suspension grade
Pooled cryopreserved human hepatocytes, female, suspension grade
Pooled cryopreserved human hepatocytes, mixed gender, suspension grade
Recommended media for pooled human hepatocytes, suspension grade:
Thawing:
Universal Cryopreserved Recovery Medium (UCRM™)
50 mL: Catalog Number 81015
Incubation:
Hepatocyte Incubation Medium (HQM™)
50 mL: Catalog Number 81039
500 mL: Catalog Number 81040
IVAL • www.invitroadmet.com • 1-410-869-9037 or 1-866-458-1094 • Email [email protected]
10
Products
Individual Human Cryopreserved Hepatocytes
IVAL offers extensive characterization on their individual donor products, which can be recommended for suspension or plated cultures, depending on the lot characteristics. Selections can be
made from multiple lots qualifying as metabolism grade, plateable/inducible grade and/or transporter grade. For best results, let us help you select the lot that will give you optimal results for your
research needs.
CATALOG
NUMBER
82001
82002
DESCRIPTION
Cryopreserved human hepatocytes, male, suspension, metabolism grade
Cryopreserved human hepatocytes, female, suspension, metabolism grade
82006
Cryopreserved human hepatocytes, plateable, male or female, inducible grade
82007
Cryopreserved human hepatocytes, plateable, male or female, inducible and
transporter grade
•Wide Selection of donors
•Large lots for long-term needs
•Extensively characterized for metabolism,
induction and transporter activities
•Custom selection process
IVAL • www.invitroadmet.com • 1-410-869-9037 or 1-866-458-1094 • Email [email protected]
11
Cryopreserved Hepatocytes: Animal
Plateable and Suspension Grade
In addition to a large inventory of human hepatocytes, IVAL offers cryopreserved hepatocytes from a
selection of toxicologically-relevant species to suit a variety of in vitro applications. Cryopreserved animal
hepatocytes are available in both suspension and plateable grades.
SPECIES
C57B6 MOUSE
CD-1 MOUSE
SD RAT
FISHER RAT
WISTAR RAT
BEAGLE DOG
CATALOG
NUMBER
82014
82015
82012
82013
82021
82031
82016
82017
82018
82019
82010
82011
82023
82024
82026
82025
82027
82028
82029
82030
DESCRIPTION
Cryopreserved C57B6 Mouse hepatocytes, male, suspension grade
Cryopreserved C57B6 Mouse hepatocytes, female, suspension grade
Cryopreserved CD-1 Mouse hepatocytes, male, suspension grade
Cryopreserved CD-1 Mouse hepatocytes, female, suspension grade
Cryopreserved CD-1 Mouse hepatocytes, male, plateable
Cryopreserved CD-1 Mouse hepatocytes, female, plateable
Cryopreserved SD Rat hepatocytes, male, suspension grade
Cryopreserved SD Rat hepatocytes, female, suspension grade
Cryopreserved SD Rat hepatocytes, male, plateable
Cryopreserved SD Rat hepatocytes, female, plateable
Cryopreserved Fisher 344 Rat hepatocytes, male, suspension grade
Cryopreserved Fisher 344 Rat hepatocytes, female, suspension grade
Cryopreserved Wistar Rat hepatocytes, male, suspension grade
Cryopreserved Wistar Rat hepatocytes, female, suspension grade
Cryopreserved Wistar Rat hepatocytes, male, plateable
Cryopreserved Wistar Rat hepatocytes, female, plateable
Cryopreserved Beagle Dog hepatocytes, male, suspension grade
Cryopreserved Beagle Dog hepatocytes, female, suspension grade
Cryopreserved Beagle Dog hepatocytes, male, plateable grade
Cryopreserved Beagle Dog hepatocytes, female, plateable grade
IVAL • www.invitroadmet.com • 1-410-869-9037 or 1-866-458-1094 • Email [email protected]
12
Products
Cryopreserved Hepatocytes: Animal, continued
Custom preparations for additional species are made on request.
CATALOG
NUMBER
SPECIES
A75715
Cryopreserved Cynomolgus Monkey hepatocytes, male, suspension grade
A75716
Cryopreserved Cynomolgus Monkey hepatocytes, female, suspension grade
Cryopreserved Cynomolgus Monkey hepatocytes, male, plateable, induction
grade
Cryopreserved Cynomolgus Monkey hepatocytes, female, plateable,
induction grade
Cryopreserved Cynomolgus Monkey hepatocytes, male, pool of 10 plateable,
induction grade
Cryopreserved Cynomolgus Monkey hepatocytes, female, pool of 10
plateable, induction grade
Cryopreserved Cynomolgus Monkey hepatocytes, male, pool of 20 plateable,
induction grade
Cryopreserved Cynomolgus Monkey hepatocytes, female, pool of 20
plateable, induction grade
Cryopreserved Cynomolgus Monkey hepatocytes, mixed, pool of 20
plateable, induction grade
Cryopreserved Cynomolgus Monkey hepatocytes, mixed, pool of 50
plateable, induction grade
Cryopreserved Rhesus Monkey hepatocytes, male, suspension
Cryopreserved Rhesus Monkey hepatocytes, female, suspension
Cryopreserved Rhesus Monkey hepatocytes, male, plateable
Cryopreserved Rhesus Monkey hepatocytes, female, plateable
Cryopreserved African Green Monkey hepatocytes, male, suspension
Cryopreserved African Green Monkey hepatocytes, female, suspension
Cryopreserved Baboon hepatocytes, male, suspension
Cryopreserved Baboon hepatocytes, female, suspension
A75245
A75246
A75701
CYNOMOLGUS
MONKEY
A75702
A75681
A75682
A75683
A75684
RHESUS
MONKEY
AFRICAN GREEN
MONKEY
BABOON
DESCRIPTION
A75309
A75310
A75713
A75714
A75551
A75552
A75663
A75664
IVAL • www.invitroadmet.com • 1-410-869-9037 or 1-866-458-1094 • Email [email protected]
13
OnDemandTM Pre-plated
Cryopreserved Hepatocytes
As more in vitro assessments migrate to
plated hepatocyte assays, reliable thawing
and plating results are increasingly important. Our OnDemand™ pre-plated cryopreserved hepatocytes
gives you all of the advantages of cryopreserved products with none of the hassle.
We’ll thaw and plate your selection for you, shipping to arrive when you choose. Our proprietary shipping
media allows up to 2 days in transit without sacrificing quality. Now, you can schedule your lab activities
without fear of poor attachment rates and other obstacles related to inexperience in thawing and plating.
OnDemand Products
(XX = well format: 06, 12, 24, 48, 96)
CATALOG NUMBER
82043-XXOD
82047-XXOD
82046-XXOD
82045-XXOD
82044-XXOD
DESCRIPTION
OnDemand™ plated cryopreserved Human hepatocytes
On Demand™ plated cryopreserved Cynomolgus Monkey hepatocytes
On Demand™ plated cryopreserved Dog hepatocytes
On Demand™ plated cryopreserved Rat hepatocytes
On Demand™ plated cryopreserved Mouse hepatocytes
IVAL • www.invitroadmet.com • 1-410-869-9037 or 1-866-458-1094 • Email [email protected]
14
Products
Genetically-Engineered Mouse (GEM) Hepatocytes
Evaluate the utility of GEM models by prescreening with hepatocytes from Taconic’s t-ADMET mouse portfolio.
These hepatocytes represent a convenient experimental tool to help design in vivo studies using GEM models
and aid data interpretation from them, bridge between human hepatocyte in vitro studies and in vivo studies
performed using GEM mouse models, enhance efficiency of in vivo studies using these models and perform
mechanistic drug metabolism studies. These cryopreserved cells are suitable for suspension incubations.
GEM Products
CATALOG NUMBER
Plateable Suspension
82041
82042
82039
82040
82037
82038
82054
82055
82056
82057
82058
82059
82035
82036
82064
82065
82066
82067
DESCRIPTION
Humanized Liver CYP3A4
Cyp3a (8-gene) Knockout
Humanized PXR-CAR-CYP3A4/3A7
Humanized OATP1B1
Humanized OATP1B3
Humanized OATP1B1/1B3
Oatp1a/1b Cluster Knockout
FVB Wildtype
C57BL/6 Wildtype
TACONIC MODEL
NUMBER
9048
9011
11585
10708
10725
11594
10707
NA
NA
mRNA Primers
RT-PCR has become a versatile tool to evaluate gene expression in toxicological and pharmacological
evaluations of new compounds, having been included in the recent draft guidance from the FDA as an
informative assay for CYP induction investigations. IVAL provides customized, validated primers for ADME-Tox
genes for use in RT-PCR analysis. Each set includes a forward and a reverse primer for the gene of interest.
Primers for housekeeping genes sold separately. Sold as a custom preparation; please call to discuss your
inquiry.
CATALOG
NUMBER
84003
DESCRIPTION
Qualified RTPCR Primers (custom)
IVAL • www.invitroadmet.com • 1-410-869-9037 or 1-866-458-1094 • Email [email protected]
15
Media & Media Kits
Media is an important part of a successful cell culture outcome, and with over 30 years of primary cell
culture experience, our media formulations are the best at optimizing hepatocyte culture conditions.
Improve your data confidence at any research application by using our specially formulated cryopreserved
hepatocyte metabolism, induction, or inhibition media. Increase cryopreserved cell plating efficiency with
our one-step universal recovery media in combination with universal plating media. Our customized cell
media also includes specially-formulated media designed for use with astrocytes, renal proximal tubule
cells, and microglial cells. All media are sterile-filtered and ready to use.
IVAL Cryopreserved Hepatocyte Characterization Kit (I-CHCK)
Our easy, one-step Universal Cryopreserved Recovery Medium (UCRM™) in combination with Universal Primary Cell Plating Medium (UPCM™) optimizes plateability for cryopreserved cells. Now this
combination comes in a convenient, single-use I-CHCK kit so you can prep your cryopreserved cells for
plating quickly and successfully. Select for the species and well format of your choice.
Each kit contains the following components:
• Tube A: Thawing Medium, 50 mL, 37°C – UCRM™ [for all species]
• Tube B: Plating Medium, 50 mL, 4°C
UPCM™ 50 mL for Human, Monkey, and Rat
IPM-A™ 50 mL for Dog and Mouse
• Tube C: Matrigel® Overlay Medium,15 mL, 4°C [for all species]
• Tube D: Induction Medium, 50 mL, 37°C
HIM™ 50 mL for Human, Monkey, and Dog
RHIM™ 50 mL for Rat and Mouse
• Trypan Blue counting solution
• Empty microcentrifuge tube for cell count dilution
• Hemocytometer
• CellAffix™ Collagen coated plate (specify well format)
• Protocol for use
CATALOG
NUMBER
85002
85003
85004
85005
DESCRIPTION
I-CHCK: IVAL Cryopreserved Hepatocyte Characterization Kit: Human and Monkey
I-CHCK: IVAL Cryopreserved Hepatocyte Characterization Kit: Rat
I-CHCK: IVAL Cryopreserved Hepatocyte Characterization Kit: Dog
I-CHCK: IVAL Cryopreserved Hepatocyte Characterization Kit: Mouse
IVAL • www.invitroadmet.com • 1-410-869-9037 or 1-866-458-1094 • Email [email protected]
16
Products
Media
Get the most from your cell culture experiments and improve your data confidence by using our specially-formulated hepatocyte incubation media for metabolism, induction, or inhibition experiments.
Our customized cell media also includes specially-formulated media designed for use with astrocyte,
renal proximal tubule and microglial cells. All media are sterile-filtered and ready to use.
Our most popular media for optimal hepatocyte performance:
Thawing--easy to use one-step procedure:
Universal Cryopreserved Recovery Medium (UCRM™)
50 mL: Catalog Number 81015
Plating--optimizes cell attachment rate:
Universal Primary Cell Plating Medium (UPCM™)
50 mL: Catalog Number 81016
500 mL: Catalog Number 81017
Suspension and Plated Assays (up to one week):
Hepatocyte Induction Medium (HIM™) with supplements
50 mL: Catalog Number 81018
500 mL: Catalog Number 81019
Long-term Plated Assays (up to 14 days):
Li’s Differentiation Maintenance Medium-A (LDMM™-A)
50 mL: Catalog Number 81001
500 mL: Catalog Number 81007
IVAL • www.invitroadmet.com • 1-410-869-9037 or 1-866-458-1094 • Email [email protected]
17
All Media Products
CATALOG
NUMBER
81001
81002
81007
81008
81013
81014
81015
81016
81017
81018
81019
81020
81021
DESCRIPTION
RECOMMENDED USE
Li’s Differentiation Maintenance Medium (LDMM™)
50mL - A
Li’s Differentiation Maintenance Medium (LDMM™)
50mL - B
Li’s Differentiation Maintenance Medium (LDMM™)
500mL - A
Li’s Differentiation Maintenance Medium (LDMM™)
500mL - B
UCRM-AF™ - Universal Cryopreserved Recovery
Medium-Animal Product Free 50mL
UPCM-AF™ - Universal Hepatocyte Primary Cell
Plating Medium-Animal Product Free 50mL
Universal Cryopreservation Recovery Medium
(UCRM™) 50mL
Universal Primary Cell Plating Medium (UPCM™)
50mL
Universal Primary Cell Plating Medium (UPCM™)
500mL
HIM™: Hepatocyte Induction Medium, 50 mL (with
Supplements)
HIM™: Hepatocyte Induction Medium, 500 mL (with
Supplements)
HIM™ Supplement kit
Long-term plated
assays, up to 14 days
HIM™: Hepatocyte Induction Medium, 500 mL
(without Supplements)
BEST
RESULTS
WITH
Human and
monkey
Rodent
Long-term plated
assays, up to 14 days
Human and
monkey
Rodent
Thawing
All Species
Plating
All Species
Thawing
All Species
Plating
Plating
Suspension and plated,
up to one week
Suspension and plated,
up to one week
Supplement for 81021
Suspension and plated,
up to one week (use
with 81020)
Human,
Monkey, Rat
Human,
Monkey, Rat
Human,
Monkey, Dog
Human,
Monkey, Dog
--Human,
Monkey, Dog
IVAL • www.invitroadmet.com • 1-410-869-9037 or 1-866-458-1094 • Email [email protected]
18
Products
All Media Products, continued
All Media Products, continued
CATALOG
NUMBER
DESCRIPTION
RECOMMENDED
USE
HIMM™: Modified Cryopreserved Hepatocyte
Induction Medium, 50 mL (with Supplements)
HIMM™: Modified Cryopreserved Hepatocyte
Induction Medium, 500 mL (with Supplements)
Hepatocyte Metabolism Media, 50 mL
(NO SALICYLAMIDE)
Hepatocyte Metabolism Medium, 500 mL
(NO SALICYLAMIDE)
Li’s Differentiation Maintenance Medium (LDMM™)
50mL - A (protein free)
Li’s Differentiation Maintenance Medium (LDMM™)
500mL - A (protein free)
Short-term inhibition
incubations, up to 6
hours
Short-term inhibition
incubations, up to 6
hours
Plated, up to one
week
Plated, up to one
week
Short-term
incubations
Short-term
incubations
Long-term plated
assays, up to 14 days
Long-term plated
assays, up to 14 days
81035
IVAL Plating Medium-A (IPM-A™), 50mL
Plating
81036
IVAL Plating Medium-A (IPM-A™), 500mL
Plating
81027
CHIM™: Cryopreserved Hepatocyte Inhibition
Medium, 50 mL
81028
CHIM™: Cryopreserved Hepatocyte Inhibition
Medium, 500 mL
81029
81030
81031
81032
81033
81034
81037
81038
81039
81040
RHIM: Rodent Hepatocyte Induction Medium, 50 mL
(with Supplements)
RHIM: Rodent Hepatocyte Induction Medium, 500 mL
(with Supplements)
HQM™ Hepatocyte Incubation Medium, 50mL, Serum
Free
HQM™ Hepatocyte Incubation Medium, 500mL,
Serum Free
Plated, up to 7 days
Plated, up to 7 days
Short term, up to 6
hours
Short term, up to 6
hours
BEST
RESULTS
WITH
All Species
All Species
Human
Human
All Species
All Species
Human
Human
Dog and
Mouse
Dog and
Mouse
Rat and
Mouse
Rat and
Mouse
All Species
All Species
IVAL • www.invitroadmet.com • 1-410-869-9037 or 1-866-458-1094 • Email [email protected]
19
Introducing IdMOC™ Technology
Integrated Discrete Multiple Organ Co-culture
Overlying Medium
Cell Type: A
B
C
Seed cells in inner wells of an
IdMOC™ plate
Incubate 4-6
hours to allow
attachment
Flood outer
chamber with
media containing
test compound
e.g. drug, growth
factor, etc
Swirl plate gently
every 4-8 hours
Overlay with
Matrigel™ to
bind cells to
plate
Incubate for
24-48 hours
Incubate
2-16 hours
Harvest cells
and/or media
and assay
IVAL • www.invitroadmet.com • 1-410-869-9037 or 1-866-458-1094 • Email [email protected]
20
Products
IdMOC® plates
Integrated Discrete Multiple Organ Co-culture (IdMOC®) is an in vitro experimental model for biomedical
research. The IdMOC® technology was developed based on the concept that the multiple organs in a human
being (or animal) are physically separated but interconnected by the systemic circulation (i.e., blood). The
IdMOC® plate consists of multiple, inner wells within a larger interconnecting chamber above. Multiple
cell types are individually cultured in the inner wells, after which the larger chamber is filled with a single,
universal medium, allowing well-to-well communication. The overlying medium can be analyzed for test
material metabolism, and individual cell types can be evaluated for possible organ-specific bioaccumulation,
cytotoxicity, and efficacy.
IdMOC® can be used to evaluate drug toxicity, drug metabolism, drug distribution, as well as anti-cancer drugs
for cytotoxicity, efficacy, and mechanism of action. It represents a more complete in vitro experimental system
than the commonly used single-cell-type in vitro systems.
Applications:
• Toxicological Evaluation
• Drug Metabolism and Pharmacokinetics
• Pharmacology
• Cell Biology
The IdMOC®plate provides a method to model in vivo mulitple-organ interaction in vitro. This patented
technology is now available in collagen coated 24- and 96-well plate formats.
CATALOG
NUMBER
71034
71035
71037
71038
71047
71048
71049
71050
DESCRIPTION
IdMOC® 24-well plate (5pk) GEN2
IdMOC® 96-well plate (5pk) GEN2
IdMOC® 24-well plate, COLLAGEN COATED (5pk) GEN2
IdMOC® 96-well plate, COLLAGEN COATED (5pk) GEN2
IdMOC® 96-well plate (5pk) GEN2-single chamber
IdMOC® 96-well plate (5pk) GEN2-two chamber
IdMOC® 96-well plate, COLLAGEN COATED (5pk) GEN2-single chamber
IdMOC® 96-well plate, COLLAGEN COATED (5pk) GEN2-two chamber
IVAL • www.invitroadmet.com • 1-410-869-9037 or 1-866-458-1094 • Email [email protected]
21
Plates and Cell Culture Vessels
CellAffix®
CellAffix® Cell Culture Coated Vessels take the uncertainty out of cell culturing. Available in standard and
custom-coated formats, each plate is coated with precision and tested for sterility to ensure high quality
results. To maintain quality standards, CellAffix® Cell Culture Coated Vessels are produced in set batch sizes
and stored at 4°C prior to shipping. If your preferred plate format is not available, contact us to place a custom
order.
CATALOG
NUMBER
71001
71002
71003
71004
71005
71006
71007
71008
71009
71010
DESCRIPTION
CellAffix® Collagen I Coated Flask, T-25 cm2, 5/pack
CellAffix® Collagen I Coated Flask, T-75 cm2, 5/pack
CellAffix® Collagen I Coated Flask, T-175 cm2, 5/pack
CellAffix® Collagen I Coated Plate, 6-well, 5/pack
CellAffix® Collagen I Coated Plate, 12-well, 5/pack
CellAffix® Collagen I Coated Plate, 24-well, 5/pack
CellAffix® Collagen I Coated Plate, 48-well, 5/pack
CellAffix® Collagen I Coated Plate, 96-well, 5/pack
CellAffix® Collagen I Coated Plate, 384-well, clear, 5/pack
CellAffix® Collagen Coated Plate, 100mm (dish), 5/pack
IVAL • www.invitroadmet.com • 1-410-869-9037 or 1-866-458-1094 • Email [email protected]
22
Services
Services
IVAL offers GLP-like services that deliver fast, informative data, aiding the rapid progression of your compounds
during drug development. Our experience in handling hepatocytes in multi-well formats allows for some
comprehensive screening approaches that other providers don’t offer. While many of our projects are routine
in nature, we are always up for some innovative collaboration when “routine” just isn’t enough. Through our
collaborative investigations, we’ve come up with some creative solutions to aid early predictions of hepatotoxicity and address some non-routine drug metabolism challenges.
ADME
Metabolite Profiling / Species Comparison
Metabolite profiling studies allow the selection of the most relevant animal model to use in pharmacokinetic
and toxicity studies during drug development; i.e., the species most closely resembling a human metabolic
profile of the new chemical entity. When done early during drug development, the information can be used
to help plan the necessary nonclinical assessments on metabolites relative to the FDA’s Safety Testing of Drug
Metabolites (MIST) guidance. The use of liver microsomes allows the evaluation of metabolites formed by
phase I oxidation (mainly P450 oxidation); while hepatocytes allow the evaluation of metabolites formed by
both phase I and phase II hepatic drug metabolizing pathways.
Metabolic Pathway Identification (Reaction Phenotyping)
Predicting the potential for drug-drug interactions with co-administered compounds starts by understanding
the metabolic pathway by which a compound is eliminated from the body. Compounds with a single route of
elimination are at high risk of causing adverse events, and so to obviate any dangerous polypharmacy situations in patients, identifying the metabolic pathway(s) of a drug candidate is required by regulatory agencies
prior to IND submission.
These studies are performed using liver microsomes in the presence of selective inhibitors for the major
CYP isoforms, thus identifying the metabolic routes involved. Quantification of the parent compound and its
metabolites are performed using HPLC-LC/MS, and the percent contribution of a specific CYP isoform towards
metabolism of the test article is reported.
CYP ENZYME
1A2
2A6
2B6
2C8
2C9
2C19
2D6
2E1
3A4/5
FDA RECOMMENDED INHIBITORS
Furafylline, Alpha-napthoflavone
Tranylcypromine, Methoxsalen, Pilocarpine, Tryptamine
Ticlopidine, Sertraline, Clopidogrel, Phencyclidine, Thiotepa
Montelukast, Quercetin, Trimethorprim, Gemfibrozil,
Rosiglitazone, Pioglitazone
Sulfaphenazole, Flucanozole, Fluvoxamine, Fluoxetine
Ticlopidine, Nootkatone
Quinidine
Diethyldithiocarbamate, Clomethiazole, Diallyldisulfide
Ketoconazole, Itracanozole, Troleandomycin, Verapamil,
Azamulin
IVAL VALIDATED INHIBITOR
Furafylline
Tranylcypromine
Clopidogrel
Montelukast
Sulfaphenazole
Ticlopidine
Quinidine
Clomethiazole
Ketoconazole
IVAL • www.invitroadmet.com • 1-410-869-9037 or 1-866-458-1094 • Email [email protected]
23
Metabolic Stability
Metabolic stability is a key drug property, which is important for both drug administration regimen design as
well as toxicity. Species comparison in metabolic stability allows the determination of which animal species is
the most appropriate model for the estimation of human metabolic stability of the test article. The use of liver
microsomes allows the evaluation of metabolic stability as results of phase I oxidation. The use of hepatocytes
allows the evaluation of both phase I oxidation and phase II conjugation.
Metabolism of Low-clearance Compounds (Plated Hepatocyte Relay Assay: PHRA)
One of the challenges of drug development is estimating the intrinsic clearance of low-turnover compounds
using previously-established approaches. Now, with the recent development of a relay assay using
cryopreserved hepatocytes, exposure time to the test system can be prolonged for an accumulated incubation
time that produces excellent prediction of human pharmacokinetics for low-clearance compounds. IVAL can
perform these relays over several days to meet the incubation times needed, customized for each compound.
Example of a 72-hour incubation study; each relay performed after a 24-hour incubation.
Relay 1
Relay 2
Pooled
Medium
Pooled
Medium
Aliquot
Aliquot
P1
P2
Day 1
P3
Day 2 (First Relay)
1)
2)
Day 3 (Second Relay)
Thaw fresh vials and plate cells (Plate 3)
Remove aliquot from plate P2, T=48h and pool
remaining drug-containing medium from
each well
After 4h replace the medium in plate P3 with
Pooled medium from P2 containing remaining
drug
Remove an aliquot immediately
after adding medium with drug. Relay-2, T=0
Incubate for 24h.
Diazepam and tolbutamide metabolism using the relay method with incubations of over 40 hours.
3)
Thaw vials and plate hepatocytes (Plate 1)
After 4h replace the medium with
medium containing drug
Remove an aliquot immediately
after adding medium with drug. T=0
Incubate cells with drug for 24h
4)
Diazepam
1)
2)
3)
4)
5)
Ln(%Remaining)
6
HH1023
HH1031
HH1036
Pool
Mean(- -)
4
2
0
-2
Thaw fresh vials and plate cells. (Plate 2)
Remove aliquot from plate P1 T=24h and pool
remaining drug-containing medium from
each well
After 4h replace the medium in plate P2 with
pooled medium from P1 containing remaining
drug (T = 24 hrs)
Remove an aliquot immediately
after adding medium with drug. Relay-1, T=0
Incubate for 24h
10
20
30
Time (hrs)
40
50
5
Ln(%Remaining)
1)
2)
3)
4)
5)
Tolbutamide
Donor 1
Donor 2
Donor 3
Pool
Mean(- -)
Day 4
4
Remove aliquot from plate P3, T=72h and pool
remaining drug-containing medium for analysis
3
2
1
0
20
40
Time (hrs)
60
80
IVAL • www.invitroadmet.com • 1-410-869-9037 or 1-866-458-1094 • Email [email protected]
24
Services
DDI
The FDA recommends the evaluation of new drug candidates for their potential to cause drug-drug
interactions, which can change the therapeutic index of a drug, causing either reduced efficacy or adverse
events, such as overdose or toxicity. Identifying a compound’s metabolites allows the assignment of major
metabolic pathways, facilitating experimental design for the evaluation of the compound’s drug-drug
interaction potential. IVAL offers DDI studies in liver microsomes and cryopreserved hepatocytes to suit your
investigative needs.
P450 Induction
Enzyme induction is a major mechanism of pharmacokinetic drug-drug interactions, and has the potential to
increase the metabolic clearance of a drug, thus compromising efficacy. Other concerns of induction are the
increased production of active metabolites, tumor formation and toxicological consequences. The potential
for adverse events due to enzyme induction is recognized by regulatory agencies worldwide and investigations
into a compound’s potential to create or be subject to such an effect is considered an important part of the
drug development regimen.
IVAL routinely performs hepatocyte-based induction studies in vitro, offering a large selection of human
and animal hepatocytes as a test system, a choice of validated luminescent and/or LC/MS assays, and quick
turnaround on the data generated.
Our 3-donor in situ induction studies feature the following:
Induction-qualified cryopreserved hepatocytes in 96-well format
Viability assessment
mRNA (Taqman probes qRT-PCR ) and/or enzymatic activities for CYPs 1A2, 2B6 and 3A4
7 concentrations of Test Article, CYP-isoform-specific positive controls (Agilent 1200-API3000 LC/MS)
EC50, Emax and fold induction are reported.
Turnaround time: 2 weeks
P450 Inhibition
A major mechanism of drug-drug interaction is the inhibition of drug metabolizing enzymes by a drug, thereby
inhibiting the metabolism of co-administered drugs, which are substrates of the inhibited pathways. This
can be performed using liver microsomes (human/animal) and hepatocytes readily available at IVAL. Choose
between luminescent (CYP3A4 only) or LC/MS validated protocols. Analyses are performed in triplicate across
seven concentrations of the test article. IC50 is reported.
IVAL • www.invitroadmet.com • 1-410-869-9037 or 1-866-458-1094 • Email [email protected]
25
Gene Expression Assay
IVAL offers accurate and quantitative RT-PCR gene expression profiling - a powerful tool for drug-drug
interaction, toxicology and pharmacology evaluation. Expression of multiple genes can be quantified
from a single mRNA sample, allowing evaluation of diverse effects. Key ADMET genes that can be readily
quantified from in vitro and in vivo samples include P450 isoforms, uptake transporters, efflux transporters,
toxicologically-relevant genes, and pharmacologically-relevant genes.
The evaluation of the effect of a drug on gene expression profiles of the human genome is considered a
valuable technique for the definition of toxicological potential. Our laboratory has developed an extensive list
of validated primer assays to allow the provision of contract research service in this area. The combined use of
hepatocytes and real-time PCR techniques allows the determination of organ-specific cytotoxicity, mechanism
of action, and potential to cause idiosyncratic hepatotoxicity. Please contact us to help you design the best
approach to use this powerful molecular tool to advance your projects.
METABOLISM
Phase I Metabolism
Phase II Metabolism
Drug Transporters
26
TOXICITY
Apoptosis
Oxidative Stress
DNA Damage
Cell Cycle Arrest
Inflammation
Carcinogenicity
Loss of Organ-specific Functions
IVAL • www.invitroadmet.com • 1-410-869-9037 or 1-866-458-1094 • Email [email protected]
Services
Toxicity
In vitro testing using primary cells can quickly screen for new chemical entities with serious toxicological
consequences. Using primary cells derived from human tissues, the relative risk can be determined in multiple
organs over a population of donors. The following in vitro
cytotoxicity assays using the specified endpoints have been developed in our laboratory.
With our ready inventory of human and animal cells, scheduling is simple. Contact IVAL to begin designing
your study today.
Primary cells validated for such studies include:
•
•
•
•
•
Hepatocytes (cryopreserved, human and animal hepatocytes)
Kidney proximal tubule epithelial cells
Astrocytes
Aortic endothelial cells
Small airway epithelial cells
Metabolism-dependent Toxicity (Utility of IdMOC®)
In most in vitro systems, each cell type is studied in isolation, leaving critical interactions between organs, such
as metabolism-based toxicity in extra-hepatic tissues, to go unrecognized. The IdMOC® system models in vivo
multiple-organ interaction, thus allowing the evaluation of organ-specific effects of a drug and its metabolites.
Customize your array of cell types as required. Inquire for further details.
Effect of hepatocyte co-culture on toxicity of cyclophosphamide to
phytohemagglutinin (PHA) stimulated and unstimulated splenocytes,
measured by viability.
PHA dose response
160
140
120
100
80
60
40
20
0
Control - Single
Control - Co-culture Cyclophosphamide Cyclophosphamide Single
Co-culture
IVAL • www.invitroadmet.com • 1-410-869-9037 or 1-866-458-1094 • Email [email protected]
27
Primary Cell Cytotoxicity Assay
In vitro testing using primary cells can quickly screen for new chemical entities with serious toxicology
consequences. Using primary cells derived from human tissues, the relative risk can be determined in multiple
organs over a population of donors. The following in vitro cytotoxicity assays using the specified endpoints
have been developed in our laboratory. Our ready inventory of characterized human and animal hepatocytes
makes scheduling easy. Contact IVAL to begin designing your study today.
•
•
•
•
Cell viability (luminescence based ATP assay)
Cell growth and survival (MTT/WST-1 metabolism)
Apoptosis (luminescence based caspase activity assay)
Oxidative Stress (luminescence based glutathione assay)
HTS / screening services
HTS CYP3A4 Assays: Inhibition, Time-Dependent Inhibition, and Induction
These assays utilize Promega’s proprietary luminogenic substrate, Luciferin-Isoproply Acetal (L-IPA), cryopreserved human hepatocytes and 384-well plate format
sDILI (384-well plate study) ROS/ATP
Severe drug-induced liver injury (sDILI) is a major concern during drug development, and a cause of regulatory
action against marketed drugs due to patient safety issues, including acute liver failure. IVAL worked with the
Center of Excellence for Bioinformatics, Division of Systems Biology, NCTR/FDA to develop an early screening
method using human hepatocytes in 384-well plates to predict DILI potential in new compounds. The assay
measures four endpoints (Reactive Oxygen Species (ROS), ATP content, GSH depletion, and Caspase 3/7 activity) over 7 concentrations at 24 hours. By combining toxic endpoints, predictions are improved over results
from individual assays. Our initial study, performed on a panel of 80 drugs with a range of known safety risks,
showed that by using ROS normalized with ATP content, severe DILI was predicted with 90% sensitivity and
88% specificity.
IVAL • www.invitroadmet.com • 1-410-869-9037 or 1-866-458-1094 • Email [email protected]
28
Services
Multiple Organ Toxicity Screening
In previous in vitro systems, each cell type was studied in isolation, ignoring critical interactions between
organs when metabolizing drugs. This led to the possibility of many factors such as inter-organ toxicity going
unrecognized in drug evaluations. The IdMOC® models in vivo multiple-organ interaction, thus allowing the
evaluation of organ-specific effects of a drug and its metabolites. Customize your array of cell types as required. Inquire for further details.
Primary Human Cells
•
•
•
•
Kidney proximal tubule cells
Liver hepatocytes
Small airway epithelial cells
Neuronal cells
Cell A
Cell B
Cell C
Cell A
Cell B
Cell C
Organ-specific Toxicity Screening
IdMOC® technology represents a more complete in vitro experimental system than the commonly-used singlecell-type platforms. Using IdMOC® plates, different cell types can be co-cultured and simultaneously treated
with a test compound. This allows for cell-cell interactions and offers a drug screening model that closely mimics in vivo conditions. Customize your array of cell types as required. Inquire for further details. We provide
service for both activity-based (phenotypic) and gene expression (real-time PCR) endpoints.
PHENOTYPIC AND GENE EXPRESSION
(QUANTITATIVE RT-PCR) ENDPOINTS FOR:
Cytotoxicity
Apoptosis
Sub-acute Toxicity
Cell cycle arrest
Oxidative Stress
DNA Damage
Inflammatory response
IdMOC® Detection of Selective Toxicity
RENAL
CELLS
HEPS
AIRWAY
CELLS
RENAL
CELLS
HEPS
AIRWAY
CELLS
HEPATOTOXICITY GENE EXPRESSION
ENDPOINTS FOR:
Phase I metabolism
Phase II metabolism
Efflux transporters
Uptake transporters
Cholestasis
Steatosis
Phospholipidosis
RENAL
CELLS
HEPS
AIRWAY
CELLS
RENAL
CELLS
HEPS
AIRWAY
CELLS
AFLATOXIN B1
AFLATOXIN B1
SELECTIVE HEPATOXICITY observed
IVAL • www.invitroadmet.com • 1-410-869-9037 or 1-866-458-1094 • Email [email protected]
29
SELECTIVE HEPATOXICITY observed
Anti-cancer Drug Screening
Using IdMOC® plates, different oncogenic cell lines and their normal counterparts can be co-cultured simultaneously. Choose from one of our screening models:
•
IdMOC® multi-cancer screening
•
IdMOC® organ-specific cancer screening
•
IdMOC® organ-specific, primary and metastatic cancer screening
•
IdMOC® organ-specific, normal and oncogenic cell line screening
endpoints measured:
Lung
Aorta
CNS
Cell viability: MTT metabolism
Cell proliferation: BrdU
incorporation
Liver
Kidney
Tumor
MCF-7
Cell survival: AKT, BAX, BCL2, BCL2L1, ELK1,
FOS, MYC, NFKB, TNFRSF11A
Cell cycle progression: Cyclin D1, Cyclin E1,
CDK2, CDK4, P21Cip1, p27Kip1, p19Ink4d,
TAMOXIFEN
p53, RB1
DNA repair: APC, ATM, BRCA1, BRCA2,
ERCC3, MSH2, XPA, XPC
Growth factor receptors: ERB1, Her-2,
ERBB3, ERBB4, FGF2R, IGF1R, IGF2R, MET
Hormone Receptors: AR, ER-α, ER-β, PPARα,
PPARδ, PPARγ, RARA, RARB, RARG, RXRA,
RXRB
Drug Metabolism: CYP1A1, CYP1A2, CYP2B6,
CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1,
CYP3A4, CYP3A5, EPHX1, GSTP1, NAT2, SOD1,
SULT1E1, TPMT, ARNT
Li AP, Bode C, Sakai Y. Chem Biol Interact. 2004 Nov 1;150(1):129-36
Drug Resistance: ABCB1, ABCC1, ABCC2,
ABCC3, ABCC5, ABCC6, ABCG2, CLPTM1L
Adverse Drug Effects (ADE) High-throughput Screening
In Vitro ADMET Laboratories (IVAL) offers a proprietary high-throughput ADE assay in human hepatocytes. This
robot-assisted assay provides reproducible and accurate results within 10 days of test article receipt. Our ADE
assay addresses the 3 most critical questions in drug development, namely, hepatotoxicity, CYP3A inhibition,
and CYP3A induction. Hepatotoxicity assay measures cell viability (ATP content) and apoptosis (caspase activity) in response to drug treatment. CYP3A4 inhibition and induction assays measure CYP3A enzyme activity in
presence of a luciferin-based CYP3A4 substrate. Rifampin (inducer of CYP3A4) and ketoconazole (inhibitor of
CYP3A4) serve as positive controls, respectively.
IVAL • www.invitroadmet.com • 1-410-869-9037 or 1-866-458-1094 • Email [email protected]
30
Training and Education
Easily accessible by public transit, IVAL’s Boston Hepatocyte Technology
Center hosts regular hands-on hepatocyte training workshops and
scientific symposia on topics of interest to drug development scientists.
This 10,000 ft2 facility allows us to expand our laboratory operations
and provide broader resources to the scientific community. Whether it’s
hands-on training, staying current on new developments or networking
with like-minded scientific professionals, this is the place for your
Complete Hepatocyte Solutions.
Hepatocyte Workshops
Our workshops are designed for industry professionals seeking to improve hepatocyte handling skills and
increase knowledge of in vitro assays for metabolism, inhibition, induction and transporters.
Participants will learn best practices and refresh their skills in such areas as:
•
•
•
•
•
Cell culture and sterile laboratory basics
Thawing procedure
Plating and suspension techniques for drug development assays
Cell counting
Demonstrations of innovative hepatocyte applications
Informational discussions will be features as part of the workshop on topics including:
• An overview of ADME-Tox
• Review of regulatory guidance regarding the use of hepatocytes and microsomes
• Emerging research on hepatocyte applications
Symposia
IVAL hosts scientific symposia and short courses throughout the year to provide the drug development
community with an opportunity to discuss the latest research regarding innovative research, with special
emphasis on hepatocytes in drug discovery and drug development applications.
Check our website for a schedule of events.
IVAL • www.invitroadmet.com • 1-410-869-9037 or 1-866-458-1094 • Email [email protected]
31
In Vitro ADMET
Laboratories, LLC
CompleteHepatocyteSolutionsTM
In Vitro ADMET Laboratories
9221 Rumsey Road, Suite 8
Columbia, MD 21045
1-410-869-9037
1-866-458-1094
9‑5 pm est
[email protected]
www.invitroadmet.com