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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