CSTA2015 Blocks-based Programming: Toolboxes for Many Occasions
Compound Libraries & Toolboxes · Stem Cells Stem Cell Reprogramming, Differentiation, Expansion...
Transcript of Compound Libraries & Toolboxes · Stem Cells Stem Cell Reprogramming, Differentiation, Expansion...
Compound Libraries & ToolboxesProduct Listing | Edition 2
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2 Compound Libraries
The TocriscreenTM range includes compound libraries and toolboxes exclusively available from Tocris. Tocriscreen compound libraries are composed of 1280 biologically active compounds, covering a range of pharmacological targets. The Tocriscreen toolboxes are collections of active compounds from the Tocris range that target specific areas of research.
Available in three sizes, the Tocriscreen compound libraries contain a mixture of commonly used standards, and the latest research tools, selected from the Tocris catalog based on their suitability for use in screening applications. These compounds are the same high-quality compounds that are found throughout the catalog. In addition to pharmacological activity, the compounds have proven solubility, purity and stability under long-term storage in DMSO.
To request the detailed compound lists for any of the Tocriscreen compound libraries or toolboxes, please visit www.tocris.com/screeningenquiry
Tocriscreen
Tocriscreen Pro and Mini compound libraries are supplied in latch racks with SepraSeal caps.
Tocriscreen Micro libraries are supplied in 96-well, v-bottom microplates.
Table of Contents:
Tocriscreen Plus Range............................................... 2-5 FDA-Approved Compounds............................................. 6Custom Libraries............................................................. 3 Other Tocriscreen Libraries............................................... 7
Key Product Information for Tocriscreen Micro, Mini and Pro
Micro Mini Pro
No. of compounds 1280 1280 1280
Volume 15 μL 50 μL 250 μL
Solution Format 10 mM DMSO 10 mM DMSO 10 mM DMSO
Seal Peelable foil seal SepraSeal Cap SepraSeal Cap
Storage Format 96-well, v-bottom microplate 96-well racks with Matrix™ storage tubes
96-well racks with Matrix™ storage tubes
Storage Temperature -20°C -20°C -20°C
Stability (for at least) 6 months, prior to opening 6 months 6 months
Matrix™ is a trademark of Thermo Fisher Scientific
3Tocriscreen Plus
Key Product Features
Custom Library Service
Major Target Classes Covered by Tocriscreen Pro, Mini and Micro
The Tocriscreen compound libraries cover a wide range of >300 pharmacological targets.
The library is fully annotated, with comprehensive documentation available including compound list, SD files and references.
Research Areas Covered by Tocriscreen Compounds
Tocriscreen Overlap with Other Compound Libraries
The 1280 compounds within the Tocriscreen compound libraries cover the most popular research areas, with coverage of up-to-date targets, including epigenetic probes and stem cell compounds.
The Tocriscreen range has low overlap with other commercially available compound libraries.
Research Area Selected Areas Included
Cancer Apoptosis, Cell Cycle, Cell Metabolism, Kinases, Cancer Stem Cells
Cardiovascular Angiotensin, Adrenergic and Vasopressin Receptors
Endocrinology Peptide Hormone Receptors, AMPK, GSK-3, PPAR
Epigenetics HDACs, KMTs, PRMTs, HATs, DMTs, MBTs
Immunology Cytokine and Chemokine Receptors, TLRs, Complement, p38
Neuroscience Neurotransmission, Neuropeptides, Nociception, Amyloid β Metabolism
Stem Cells Stem Cell Reprogramming, Differentiation, Expansion
No. Compounds Tocriscreen Plus Overlap
LOPAC 1280 15%
Spectrum 2560 10%
Prestwick 1280 10%
Selleck Chemicals 3861 32%
This is a unique service designed to meet your exact screening requirements. Specify compounds, quantities, format (dry or DMSO) and the tube, vial or plate required. The Tocris scientific team can also provide assistance in choosing compounds that are relevant to your research requirements.
• Cherry-pick from the Tocriscreen to create your own custom DMSO library
• Modules of the library available as toolboxes for kinase inhibitors, epigenetics and stem cells
• Guaranteed resupply of compounds within 6 months of purchase
GPCRs27%
Nuclear receptors5%
Transporters and otherpharmacology
5%
Cell biology10%
Ion channels14%
Enzymes (non-kinases)19%
Kinases inc. enzyme-linked receptors20%
4 Compound Libraries
Tocriscreen
Physicochemical Properties
Analysis of the physicochemical properties of the compounds in Tocriscreen compound libraries demonstrates that the majority of compounds are compliant with Lipinski’s Rule of Five (RO5)* which is a guide used to evaluate the characteristics of orally active, drug-like molecules. Compounds which have ‘no more than one ’ violation of these criteria are more likely to be membrane permeable and easily absorbed by the body.
The majority of compounds (94%) included in the range have ‘no more than one’ RO5 violation with the remaining compounds being predominantly clinically approved drugs.
An Overview of the Calculated Properties of the Library
% of compounds compliant with Lipinski’s Rules
PhysChem Properties % Compounds
<5 Hydrogen-bond donors 98
<10 Hydrogen-bond acceptors 96
cLogP <5 79
Mol Weight <500 daltons 89
500
400
300
200
100
0-15
0
601-
1000
501-
600
401-
500
301-
400
Molecular weight
Distribution of Molecular weight
No.
of
com
poun
ds
151-
300
0
500
600
700
800
400
300
200
100
7–104–61–3-2 –0
cLogP
Distribution of cLogP
No.
of
com
poun
ds
-7– -30
500
600
400
300
200
100
0 5432
HB Donor Count
Distribution of HB Donors
Distribution of HB Acceptors
No.
of
com
poun
ds
1 6
≥
≥0
300
200
100
0 5432
HB Acceptor Count
No.
of
com
poun
ds
1 6 70
500
400
300
200
100
0-15
0
601-
1000
501-
600
401-
500
301-
400
Molecular weight
Distribution of Molecular weight
No.
of
com
poun
ds
151-
300
0
500
600
700
800
400
300
200
100
7–104–61–3-2 –0
cLogP
Distribution of cLogP
No.
of
com
poun
ds
-7– -30
500
600
400
300
200
100
0 5432
HB Donor Count
Distribution of HB Donors
Distribution of HB Acceptors
No.
of
com
poun
ds
1 6
≥
≥0
300
200
100
0 5432
HB Acceptor Count
No.
of
com
poun
ds
1 6 70
500
400
300
200
100
0-15
0
601-
1000
501-
600
401-
500
301-
400
Molecular weight
Distribution of Molecular weight
No.
of
com
poun
ds
151-
300
0
500
600
700
800
400
300
200
100
7–104–61–3-2 –0
cLogP
Distribution of cLogP
No.
of
com
poun
ds
-7– -30
500
600
400
300
200
100
0 5432
HB Donor Count
Distribution of HB Donors
Distribution of HB Acceptors
No.
of
com
poun
ds
1 6
≥
≥0
300
200
100
0 5432
HB Acceptor Count
No.
of
com
poun
ds
1 6 70
500
400
300
200
100
0-15
0
601-
1000
501-
600
401-
500
301-
400
Molecular weight
Distribution of Molecular weight
No.
of
com
poun
ds
151-
300
0
500
600
700
800
400
300
200
100
7–104–61–3-2 –0
cLogP
Distribution of cLogP
No.
of
com
poun
ds
-7– -30
500
600
400
300
200
100
0 5432
HB Donor Count
Distribution of HB Donors
Distribution of HB Acceptors
No.
of
com
poun
ds
1 6
≥
≥0
300
200
100
0 5432
HB Acceptor Count
No.
of
com
poun
ds
1 6 70
Molecular weight
cLog
P
cLogP vs MW15
10
5
0
-5
-100 100 200 300 400 500 600 700 800 900 1000
* Lipinski et al (2001). Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Advanced Drug Discovery Reviews. 46 3. PMID 11259830
5Tocriscreen Plus
Applications of the Tocriscreen Compound Library
Drug Repurposing – screening of compound libraries can reveal new uses for existing drugs, which can accelerate the drug discovery process
Drug repurposing screening identifies novel compounds that effectively inhibit toxoplasma gondii growthDittmar et al. (2016) mSphere. 1 e0042. PMID: 27303726
This study used Tocriscreen to identify compounds that inhibit the growth of the parasite Toxoplasma gondii.
Discovery of New Tools – screening of compound libraries can lead to the identification of new tools which complement new applications e.g. CRISPR
Small molecules enhance CRISPR genome editing in pluripotent stem cells Yu et al. (2015) Cell Stem Cell 16 142. PMID: 25658371
This study used Tocriscreen to identify compounds that enhance CRISPR efficiency using an imaging-based small molecule screen.
Assay Validation – the use of established compound libraries enables researchers to validate their assays while screening for new tools.
Screening for novel LRRK2 inhibitors using a high-throughput TR-FRET cellular assay for LRRK2 ser935 phosphorylation Hermanson et al. (2012) Plos One 7 e43580. PMID 22952710
This study used Tocriscreen to screen for novel LRRK2 inhibitors. Six direct inhibitors of LRRK2 were identified.
LRRK2-IN-1 (#4273) was used as a positive control to validate the assay
Compound
Log 2
(%
par
asit
e gr
owth
inhi
biti
on)
200
ND
-12
-8
-4
0
4
0 400 600 800 1000 1200
Graphic representation of screening data showing chemical compounds that inhibit Toxoplasma gondii growth. Blue squares – no host cell toxicity; red triangles – host cell toxicity.
The estrogen receptor antagonist tamoxifen and the dopamine D2 receptor antagonist pimozide from Tocris were found to block Toxoplasma gondii growth and replication.
Hits Identified
Et
OMe2N
F
F
N
N
NHO
Tamoxifen (#0999)
Pimozide (#0937)
NH
SNH
OO
HN
OOH
OH
NH
O
HN
O
O
O
N3
OH
N
L-755,507 (#2197)
Increases homology-directedrepair (HDR) efficiency
Decreases homology-directedrepair (HDR) efficiency
Azidothymidine (#4150)
Screening results showing a frequency distribution of the compounds’ % inhibition of LRRK2
Percent inhibition
Freq
uenc
y
0
10
20
30
40
50
-50 -25 0 25 50 75 100
6 Compound Libraries
Tocriscreen Library of FDA-Approved CompoundsDrug–repurposing is a key strategy in the drug discovery process. Previously approved drugs have the advantage of being fully evaluated for efficacy and have known safety data, which can accelerate the drug discovery process.
This library of compounds is a sub-set of Tocriscreen Plus library, and contains 159 FDA-approved compounds, which have the same proven solubility, biological activity and stability as the products found in the Tocriscreen Plus compound libraries.
Product Cat. no No. Compounds Vol. Format
Tocriscreen FDA-Approved Compounds 5932 159 250 μl 10 mM DMSO
Product Format• Compounds supplied in 0.75 ml 2D barcoded V bottom MatrixTM storage tubes, with pre-split SepraSeal
caps, and arranged in latch racks, with 2 racks per library.
• Barcodes and human readable labels on each latch rack for easy identification
Key Product Features • All compounds are FDA-approved
• Fully annotated library – biological activity and known targets are specified
• Includes both established therapeutics e.g. tamoxifen (#0999) and paclitaxel (#1097), as well as more recent compounds e.g. gefitinib (#3000) and axitinib (#4350)
• Extensive compound details available in Excel and SD file format
To request the detailed compound lists for any of the Tocriscreen compound libraries or toolboxes, please visit www.tocris.com/screeningenquiry
* Data derived using the WHO Anatomical Therapeutic Chemical Classification System code (ATC code)
Therapeutic Classification*
% Total Library
0 5 10 15 20 25
Alimentary tract and metabolism
Blood and blood forming organs
Cardiovascular system
Dermatalogicals
Genitourinary system and sex hormones
General anti-infectives for systemic use
Antineoplastic and immunomodulating agents
Musculo skeletal system
Nervous system
Antiparasitic system
Respiratory system
Sensory organs
Various
Unclassified
Molecular Weight
cLog
P
Physicochemical properties – cLogP vs MW
7.5
10.0
5.0
2.5
0
-2.5
-7.5
-5.0
0 250 500 750 1000
The library covers a range of therapeutic classes including the cardiovascular and nervous system, as well as research areas such as cancer and immunology
86% of compounds have cLogP <5 87% of compounds have Mol. Weight <500 daltons
7Tocriscreen Plus
The focused Tocriscreen Libraries are single-plate collections of biologically active compounds from the Tocris range that target specific research areas. The compounds have been chosen to provide the best and most up-to-date chemical probes for a target class or research area. Compounds included have the same proven solubility, purity and stability as the products found in the Tocris catalog.
Product Format • Compounds supplied in 1.4 ml alphanumeric coded tubes, in snap racks with SepraSeal caps
• Full chemical and biological data available
• All compounds are the same chemical standard as those found in the Tocris catalog
To request the detailed compound lists for any of the Tocriscreen compound libraries or toolboxes, please visit www.tocris.com/screeningenquiry
Focused Tocriscreen Libraries
Product Cat.no Description
Stem Cell Toolbox 5060 80 Stem Cell modulators supplied pre-dissolved in DMSO (250 µl 10 mM solutions)
Kinase Inhibitor Toolbox 6268 157 kinase inhibitor compounds supplied pre-dissolved in DMSO (250 µl 10 mM solutions)
Epigenetics Library 6801 101 Epigenetic modulators supplied pre-dissolved in DMSO (250 µl 10 mM solutions)
Tocriscreen Kinase Inhibitor Toolbox
The Tocriscreen Kinase Inhibitor Toolbox contains 157 compounds targeting >60 different kinases. This includes extensive coverage of well established targets such as VEGFR, AKT and TGFβR as well as more novel targets.
No.
of
Com
poun
ds
8
9
10
7
6
5
4
3
2
1
0
p38
MA
PK
TGF-β
Rec
epto
rs
IκB
Kin
ase
Raf
kin
ases
JAK
kin
ase
BM
P
EGFR Akt
Pro
tein
Kin
ase
C
VEG
FR
CD
Ks
Cas
ein
Kin
ase
1
Cas
ein
Kin
ase
2
Che
ckpo
int K
inas
es
ATM
/ATR
Insu
lin a
nd In
sulin
-like
rec
epto
rs
Pol
o-lik
e K
inas
e
Rho
kin
ase
PI 3
-kin
ase
Src
kina
ses
Foca
l Adh
esio
n K
inas
e
PD
GFR
Mon
opol
ar S
pind
le 1
Kin
ase
mTO
R
LRR
K2
RSK
LIM
K
MET
Aur
ora
Kin
ases
DYR
K
PER
K
JNK
/c-J
un
PD
K1
ERK
GSK
3
MEK
Has
pin
Also contains inhibitors of novel targets including:
MAP3K8 MK2MSK1 NUAK1PAK1 PIP5K1CSETD8 SGK1SPRK1 STK33
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