CDAS|Safety Pharmacology

ADMEScreen - Complete ADME-Tox Solutions
ADME Tox is an area of drug development for assessing the potential safety concerns for new compound entities (NCEs). ADME Tox studies evaluate how a drug and/or its metabolites are absorbed,
distributed, metabolized, and excreted from the body. Drug metabolism issues are one of the primary reasons why drug candidates fail in clinical trials.
ADMEScreen is a suite of programs aimed at different stages of ADME drug development ranging
from in vitro DMPK (Discovery ADME) to Maximum Tolerated Dose and PK studies (Development
ADME) to Pharmacokinetic Characterization. Our staff can provide you with bioavailability of your
compound by designing PK studies followed by a thorough analysis of your sample through LC/MS
method development and bioanalysis.
Discovery ADME
In vitro DMPK screens are tools for early stage lead candidate assessments. PAMPA (membrane permeability), CaCO-2 and MDCK (gut and renal absorption), CYP450 inhibition and induction, S9 and
microsomal stability (metabolic stabilities), as well as other in vitro metabolic screens, are a suite
of tools necessary to triage, characterize, and rank lead compounds.
Development ADME
CDAS Development ADME program are customized programs which can include Maximum Tolerated Dose (MTD) as well as other PK
studies.
These are useful tools to characterize lead compounds for in vivo acute toxicities via multiple (or different) routes of drug administration ( i.p., i.v., p.o.). These studies also can provide LDLo values of lead compounds in a specified rodent species by a specified route.
Pharmacokinetic Characterization
CDAS' pharmacokinetic characterizations studies provide drug concentration at specific time points of specified organs, such as the
brain, liver, heart, lung, kidney, pancreas, and plasma; non-compartmentalized analysis of AUC (areas under the curve), Tmax, Cmax
and calculated bioavailability.
Pharmacoinformatics - Side Effect Database (SED) Program
CDAS offers a major addition to the PROFILE toolbox through the creation of our pharmacoinformatics program, the Side Effect
Database (SED). Our SED contains profile data for more than 2,300 compounds including marketed, failed, withdrawn, and OTC drugs
as well as reference agents, agrochemicals and natural product compounds which have been screened through 65 ligand binding and
enzyme assays. The result is a highly enriched, full-rank compound dataset of more than a half a million datapoints to assist in identifying and eliminating side effect and safety concerns for your drug candidates.
The SED is designed to help you query and determine patterns of chemical - molecular target interactions that are correlated with specific biological activities or clinical outcomes. With the SED, you can select lead compounds at an early stage with increased confidence
and accuracy.
Applications of the CDAS SED:
Caliper Discovery Alliances & Services (CDAS), formed after the integration of
NovaScreen Biosciences, an in vitro service provider and Xenogen
Biosciences, an in vivo division offering target and compound evaluation
programs, has assembled a wide range of research solutions that enable
pharmaceutical companies to reduce costs while accelerating the pace and
clinical relevance of drug discovery research.
Full SED Database
Access to the full database
SEDSelect
Clients can select PROFILE data for specific compounds listed in the SED database
SED Comparative Pharmacology Services
Client compound(s) are profiled through the same SED assay set and the profile
data are then compared with the compounds in the CDAS side effect database.
Discovery Alliances & Services
Preclinical Contract Services
7170 Standard Drive
Hanover, Maryland 21076-1334 USA
Tel: 1.410.712.4410 / 1.800.543.4141
CDAS | Safety Pharmacology
Pharmacology profiling has become an invaluable tool for lead compound
selection, optimization and candidate prioritization. Analysis of profile data
identifies off-target interactions that can help predict potential side-effects,
efficacy and safety of compounds under development before they progress
to the more costly stages of preclinical and clinical trials. CDAS offers many
in vitro profile programs to fit your drug discovery & development needs.
©2010 Caliper Life Sciences, Inc. All rights reserved.
Caliper, the Caliper logo, CDAS and Discovery Alliances & Services
are tradenames and/or trademarks of Caliper Life Sciences, Inc.
All other names are trademarks of their respective companies.
CDAS-BR-04 Feb10
CDAS also offers a comprehensive in vivo compound profiling program to
assess the therapeutic efficacy of lead or optimized lead compounds by analyzing their effects on key physiological functions in animals, or possibly, by
screening for potential side effects caused by the administration of such
compound(s).
CDAS Overview
CDAS Overview
Established PROFILE Services for Over 18 Years
Additional PROFILE Programs
PROFILEing lead drug candidates through broad assay panels is now the industry
standard for side effect, selectivity and off-target effect assessment.
Addiction Liability PROFILE
KinaseAdvisor Diversity PROFILE
KinaseScreen
- Side Effect PROFILEs
Human Isogenic Cell Lines
KinaseScreen is an extensive suite of kinase services created by
CDAS to assist researchers in accelerating and optimizing compound screening, lead identification and optimization efforts.
- KinaseAdvisor Diversity PROFILE
Cell Line PROFILE
KinaseScreen PROFILEing
- GPCR PROFILE
Customized PROFILE
Anti-cancer Cell Proliferation PROFILE
CDAS offers many PROFILE programs to fit your drug discovery & development needs
- Phosphodiesterase (PDE) PROFILE
- Histone Deacetylase (HDAC) PROFILE
- Therapeutic PROFILEs
KinaseAdvisor Diversity PROFILE
Our programs answer specific needs for both large and highly customizable assay panels and for quick (less than a week turnaround
time) kinase profiling.
GPCR PROFILE
KinaseScreen HTS
Side Effect PROFILEs
In Addition to Our Standard PROFILE Services, CDAS Offers:
- General Side Effect (GEN SEP)
Over 950 standard assays relevant to the discovery and development of drug candidates
- General Side Effect II (GEN SEP II)
- HTS
- CNS Side Effect (CNS SEP)
- PROFILEing
- Side Effect (SED) Comparative Pharmacology
- Lead selectivity testing
Therapeutic PROFILEs
- Drug optimization
- Cardiovascular/Renal
Custom Services
- Cancer/Immunology
- Assay development
- Gastroinestinal
- Cell/molecular biology
- Metabolic
Pharmacoinformatics database programs
- Pain/Inflammation
Membrane preparations for screening
- Neurological
Whether you need ‘one-off’ projects or custom drug discovery programs from HTS to PROFILEing to lead optimization, CDAS is ready to
work with you as your drug discovery and development partner.
Screen your library of compounds in any kinase assay developed as
part of the CDAS KinaseScreen program. All screening projects are
highly customized to meet our clients’ expectations of throughput,
process & workflow and screening data reporting.
KinaseScreen IC50
Determine compound
inhibitor potency
KinaseScreen Mechanism
of Action (MoA)
Mechanism of Action studies
provide detailed information
about the manner in which
compounds interact with
enzymatic targets and are
important for characterizing
allosteric inhibitors and assessing kinetic on and off rates.
PROFILE Programs
Our GEN SEP II is the next generation to the popular GEN SEP PROFILE. The GEN SEP II incorporates receptor subtype assays, many of
which use human source material. These replace the non-selective assays using non-human receptor sources that comprise the GEN SEP I.
GEN SEP II continues to span a wide range of therapeutic and side effect targets.
General Side Effect PROFILE II (GEN SEP II)
Opiate, Mu (h)
Customized Screening Programs and Assay Development
Assay Development
CDAS develops more than 50 assays per year for our clients. We incorporate broad technology platforms and detection methods providing flexible assay development projects.
Some of the technology platforms and detection methods available at CDAS include:
Caliper LabChip 3000, Luminex xMAP®, FACSArrayTM, EnVisionTM and FlexStation.
Adenosine, A1
Endothelin, ETA (h)
Ion Channel, Cl- TBOB Site
Adenosine, A2A (h)
Esterase, Acetylcholine
Ion Channel hERG (I[Kr])(h)
Phosphodiesterase PDE4A1A
Adenosine, Transporter (h)
GABA A, Agonist Site
Ion Channel, K+ ATP-Sensitive
Phosphodiesterase PDE5A1
Adrenergic, α1A
GABA A, BDZ, α1 Site
Ion Channel, K+ Ca2+ Act., VI
PKA kinase
Adrenergic, α1B
GABA B
Ion Channel, Na+ Site 2
PKCα kinase
Adrenergic, α2A (h)
Glutamate, AMPA Site
Leukotriene, BLT (LTB4)
Serotonin, 5HT1A (h)
Adrenergic, α2B
Glutamate, Kainate Site
Leukotriene, CysLT1 (LTD4)
Serotonin, 5HT1D
Adrenergic, α2C (h)
Glutamate, MK-801 Site
Muscarinic, M1 (h)
Serotonin, 5HT2A
- GPCRs
- Transport
Adrenergic, β1 (h)
Glutamate, NMDA, Agonist Site
Muscarinic, M2 (h)
Serotonin, 5HT2C
- Voltage- & Ligand-gated Ion channels
- Second messenger
Adrenergic, β2 (h)
Glutamate, NMDA, Glycine
(Strychnine-insensitive) Site
Muscarinic, M3 (h)
Serotonin, 5HT3
- Nuclear receptors
Angiotensin II, AT1 (h)
Glutamate, NMDA, PCP Site
Muscarinic, M4 (h)
Serotonin, 5HT4
Bradykinin, BK2
Glycine, Strychnine-sensitive
Muscarinic, M5 (h)
Serotonin, 5HT5A (h)
- Cellular release of cytokines and
chemokines using human cell lines
and Toll-Like Receptors expressed
in HEK293 cells
Dopamine, D1 (h)
Histamine, H1
Neurokinin, NK1
Serotonin, 5HT6 (h)
Dopamine, D2s (h)
Histamine, H2
Neuropeptide, NPY2 (h)
Serotonin, 5HT7 (h)
Dopamine, D3
Histamine, H3
Nicotinic, α-Bungarotoxin-insensitive
Serotonin Transporter
Dopamine, D4.4 (h)
Ion Channel, Ca2+ Type L
Nitric Oxide Synthase, cNOS
Sigma, S1
Dopamine Transporter
Ion Channel, Ca2+ Type N
Norepinephrine Transporter
Sigma, S2
Opiate, Delta 2 (h)
Thromboxane, TXA2 (h)
Customized Screening Programs
In addition to drug profiling, CDAS offers a growing portfolio of over 650 assays that are available for your high-throughput screening, ‘oneoff’ lead selectivity or lead optimization projects. Each of these assays has been fully validated in our laboratories and we employ rigorous
QA/QC measures to ensure the data you receive is of the highest quality.
Ligand Binding Assays
- Transporters
Enzyme Assays
- Anhydrases & Esterases
- Kinases (including protein & lipid)
- Miscellaneous (COMT, ChaT, GAD)
- Phosphatases
- Proteases (Caspase & Matrix-Metallo)
- Oxidases, Oxygenases & Reductases
In Vitro Antimicrobial Assays
- Fungi
- Gram negative & positive bacteria
Cell-Based and Functional Assays
- Cell surface markers
In Vitro ADME-TOX Assays
- Apoptosis (enzyme inhibition & activation)
- Proliferation & Viability
- Cytotoxicity (mechanism-based: cellular respiration,
metabolism & anabolism)
- Metabolism (Cytochrome P450, drug stability,
drug half-life, mitochondrial electron transfer)
CDAS Overview
CDAS Overview
Established PROFILE Services for Over 18 Years
Additional PROFILE Programs
PROFILEing lead drug candidates through broad assay panels is now the industry
standard for side effect, selectivity and off-target effect assessment.
Addiction Liability PROFILE
KinaseAdvisor Diversity PROFILE
KinaseScreen
- Side Effect PROFILEs
Human Isogenic Cell Lines
KinaseScreen is an extensive suite of kinase services created by
CDAS to assist researchers in accelerating and optimizing compound screening, lead identification and optimization efforts.
- KinaseAdvisor Diversity PROFILE
Cell Line PROFILE
KinaseScreen PROFILEing
- GPCR PROFILE
Customized PROFILE
Anti-cancer Cell Proliferation PROFILE
CDAS offers many PROFILE programs to fit your drug discovery & development needs
- Phosphodiesterase (PDE) PROFILE
- Histone Deacetylase (HDAC) PROFILE
- Therapeutic PROFILEs
KinaseAdvisor Diversity PROFILE
Our programs answer specific needs for both large and highly customizable assay panels and for quick (less than a week turnaround
time) kinase profiling.
GPCR PROFILE
KinaseScreen HTS
Side Effect PROFILEs
In Addition to Our Standard PROFILE Services, CDAS Offers:
- General Side Effect (GEN SEP)
Over 950 standard assays relevant to the discovery and development of drug candidates
- General Side Effect II (GEN SEP II)
- HTS
- CNS Side Effect (CNS SEP)
- PROFILEing
- Side Effect (SED) Comparative Pharmacology
- Lead selectivity testing
Therapeutic PROFILEs
- Drug optimization
- Cardiovascular/Renal
Custom Services
- Cancer/Immunology
- Assay development
- Gastroinestinal
- Cell/molecular biology
- Metabolic
Pharmacoinformatics database programs
- Pain/Inflammation
Membrane preparations for screening
- Neurological
Whether you need ‘one-off’ projects or custom drug discovery programs from HTS to PROFILEing to lead optimization, CDAS is ready to
work with you as your drug discovery and development partner.
Screen your library of compounds in any kinase assay developed as
part of the CDAS KinaseScreen program. All screening projects are
highly customized to meet our clients’ expectations of throughput,
process & workflow and screening data reporting.
KinaseScreen IC50
Determine compound
inhibitor potency
KinaseScreen Mechanism
of Action (MoA)
Mechanism of Action studies
provide detailed information
about the manner in which
compounds interact with
enzymatic targets and are
important for characterizing
allosteric inhibitors and assessing kinetic on and off rates.
PROFILE Programs
Our GEN SEP II is the next generation to the popular GEN SEP PROFILE. The GEN SEP II incorporates receptor subtype assays, many of
which use human source material. These replace the non-selective assays using non-human receptor sources that comprise the GEN SEP I.
GEN SEP II continues to span a wide range of therapeutic and side effect targets.
General Side Effect PROFILE II (GEN SEP II)
Opiate, Mu (h)
Customized Screening Programs and Assay Development
Assay Development
CDAS develops more than 50 assays per year for our clients. We incorporate broad technology platforms and detection methods providing flexible assay development projects.
Some of the technology platforms and detection methods available at CDAS include:
Caliper LabChip 3000, Luminex xMAP®, FACSArrayTM, EnVisionTM and FlexStation.
Adenosine, A1
Endothelin, ETA (h)
Ion Channel, Cl- TBOB Site
Adenosine, A2A (h)
Esterase, Acetylcholine
Ion Channel hERG (I[Kr])(h)
Phosphodiesterase PDE4A1A
Adenosine, Transporter (h)
GABA A, Agonist Site
Ion Channel, K+ ATP-Sensitive
Phosphodiesterase PDE5A1
Adrenergic, α1A
GABA A, BDZ, α1 Site
Ion Channel, K+ Ca2+ Act., VI
PKA kinase
Adrenergic, α1B
GABA B
Ion Channel, Na+ Site 2
PKCα kinase
Adrenergic, α2A (h)
Glutamate, AMPA Site
Leukotriene, BLT (LTB4)
Serotonin, 5HT1A (h)
Adrenergic, α2B
Glutamate, Kainate Site
Leukotriene, CysLT1 (LTD4)
Serotonin, 5HT1D
Adrenergic, α2C (h)
Glutamate, MK-801 Site
Muscarinic, M1 (h)
Serotonin, 5HT2A
- GPCRs
- Transport
Adrenergic, β1 (h)
Glutamate, NMDA, Agonist Site
Muscarinic, M2 (h)
Serotonin, 5HT2C
- Voltage- & Ligand-gated Ion channels
- Second messenger
Adrenergic, β2 (h)
Glutamate, NMDA, Glycine
(Strychnine-insensitive) Site
Muscarinic, M3 (h)
Serotonin, 5HT3
- Nuclear receptors
Angiotensin II, AT1 (h)
Glutamate, NMDA, PCP Site
Muscarinic, M4 (h)
Serotonin, 5HT4
Bradykinin, BK2
Glycine, Strychnine-sensitive
Muscarinic, M5 (h)
Serotonin, 5HT5A (h)
- Cellular release of cytokines and
chemokines using human cell lines
and Toll-Like Receptors expressed
in HEK293 cells
Dopamine, D1 (h)
Histamine, H1
Neurokinin, NK1
Serotonin, 5HT6 (h)
Dopamine, D2s (h)
Histamine, H2
Neuropeptide, NPY2 (h)
Serotonin, 5HT7 (h)
Dopamine, D3
Histamine, H3
Nicotinic, α-Bungarotoxin-insensitive
Serotonin Transporter
Dopamine, D4.4 (h)
Ion Channel, Ca2+ Type L
Nitric Oxide Synthase, cNOS
Sigma, S1
Dopamine Transporter
Ion Channel, Ca2+ Type N
Norepinephrine Transporter
Sigma, S2
Opiate, Delta 2 (h)
Thromboxane, TXA2 (h)
Customized Screening Programs
In addition to drug profiling, CDAS offers a growing portfolio of over 650 assays that are available for your high-throughput screening, ‘oneoff’ lead selectivity or lead optimization projects. Each of these assays has been fully validated in our laboratories and we employ rigorous
QA/QC measures to ensure the data you receive is of the highest quality.
Ligand Binding Assays
- Transporters
Enzyme Assays
- Anhydrases & Esterases
- Kinases (including protein & lipid)
- Miscellaneous (COMT, ChaT, GAD)
- Phosphatases
- Proteases (Caspase & Matrix-Metallo)
- Oxidases, Oxygenases & Reductases
In Vitro Antimicrobial Assays
- Fungi
- Gram negative & positive bacteria
Cell-Based and Functional Assays
- Cell surface markers
In Vitro ADME-TOX Assays
- Apoptosis (enzyme inhibition & activation)
- Proliferation & Viability
- Cytotoxicity (mechanism-based: cellular respiration,
metabolism & anabolism)
- Metabolism (Cytochrome P450, drug stability,
drug half-life, mitochondrial electron transfer)
ADMEScreen - Complete ADME-Tox Solutions
ADME Tox is an area of drug development for assessing the potential safety concerns for new compound entities (NCEs). ADME Tox studies evaluate how a drug and/or its metabolites are absorbed,
distributed, metabolized, and excreted from the body. Drug metabolism issues are one of the primary reasons why drug candidates fail in clinical trials.
ADMEScreen is a suite of programs aimed at different stages of ADME drug development ranging
from in vitro DMPK (Discovery ADME) to Maximum Tolerated Dose and PK studies (Development
ADME) to Pharmacokinetic Characterization. Our staff can provide you with bioavailability of your
compound by designing PK studies followed by a thorough analysis of your sample through LC/MS
method development and bioanalysis.
Discovery ADME
In vitro DMPK screens are tools for early stage lead candidate assessments. PAMPA (membrane permeability), CaCO-2 and MDCK (gut and renal absorption), CYP450 inhibition and induction, S9 and
microsomal stability (metabolic stabilities), as well as other in vitro metabolic screens, are a suite
of tools necessary to triage, characterize, and rank lead compounds.
Development ADME
CDAS Development ADME program are customized programs which can include Maximum Tolerated Dose (MTD) as well as other PK
studies.
These are useful tools to characterize lead compounds for in vivo acute toxicities via multiple (or different) routes of drug administration ( i.p., i.v., p.o.). These studies also can provide LDLo values of lead compounds in a specified rodent species by a specified route.
Pharmacokinetic Characterization
CDAS' pharmacokinetic characterizations studies provide drug concentration at specific time points of specified organs, such as the
brain, liver, heart, lung, kidney, pancreas, and plasma; non-compartmentalized analysis of AUC (areas under the curve), Tmax, Cmax
and calculated bioavailability.
Pharmacoinformatics - Side Effect Database (SED) Program
CDAS offers a major addition to the PROFILE toolbox through the creation of our pharmacoinformatics program, the Side Effect
Database (SED). Our SED contains profile data for more than 2,300 compounds including marketed, failed, withdrawn, and OTC drugs
as well as reference agents, agrochemicals and natural product compounds which have been screened through 65 ligand binding and
enzyme assays. The result is a highly enriched, full-rank compound dataset of more than a half a million datapoints to assist in identifying and eliminating side effect and safety concerns for your drug candidates.
The SED is designed to help you query and determine patterns of chemical - molecular target interactions that are correlated with specific biological activities or clinical outcomes. With the SED, you can select lead compounds at an early stage with increased confidence
and accuracy.
Applications of the CDAS SED:
Caliper Discovery Alliances & Services (CDAS), formed after the integration of
NovaScreen Biosciences, an in vitro service provider and Xenogen
Biosciences, an in vivo division offering target and compound evaluation
programs, has assembled a wide range of research solutions that enable
pharmaceutical companies to reduce costs while accelerating the pace and
clinical relevance of drug discovery research.
Full SED Database
Access to the full database
SEDSelect
Clients can select PROFILE data for specific compounds listed in the SED database
SED Comparative Pharmacology Services
Client compound(s) are profiled through the same SED assay set and the profile
data are then compared with the compounds in the CDAS side effect database.
Discovery Alliances & Services
Preclinical Contract Services
7170 Standard Drive
Hanover, Maryland 21076-1334 USA
Tel: 1.410.712.4410 / 1.800.543.4141
CDAS | Safety Pharmacology
Pharmacology profiling has become an invaluable tool for lead compound
selection, optimization and candidate prioritization. Analysis of profile data
identifies off-target interactions that can help predict potential side-effects,
efficacy and safety of compounds under development before they progress
to the more costly stages of preclinical and clinical trials. CDAS offers many
in vitro profile programs to fit your drug discovery & development needs.
©2010 Caliper Life Sciences, Inc. All rights reserved.
Caliper, the Caliper logo, CDAS and Discovery Alliances & Services
are tradenames and/or trademarks of Caliper Life Sciences, Inc.
All other names are trademarks of their respective companies.
CDAS-BR-04 Feb10
CDAS also offers a comprehensive in vivo compound profiling program to
assess the therapeutic efficacy of lead or optimized lead compounds by analyzing their effects on key physiological functions in animals, or possibly, by
screening for potential side effects caused by the administration of such
compound(s).