TimTec History Highlights
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1995: TimTec Corporation was established in USA, Delaware as a
distributor of Zelinsky Institute (Moscow, Russia) and also began
providing compounds weighing and handling services
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1996-97: TimTec expands compound sources to numerous research
centers around the world
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1998-2004: Cheminformatics technology development, database
management, broadened supplier sources; became one-stop
shopping vendor for screening compounds; partnership with SigmaAldrich (LOPAC), BioMol (MaxiVerse), Nacalai Tesque.
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2005-2007: 10-year anniversary. New products: ApexScreen,
Natural Products and MyriaScreen (Sigma-Aldrich). Collaboration
with EnBioTec, Japan, screening, lead discovery project.
TimTec
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Headquarters in Newark, Delaware, USA
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Operations
Database management
Marketing and business development
Supplier network management
Computational services
Compound management and storage facilities
Liquid handling, labeling and bar-coding
services
Currently expanding facility, personnel and
instrumentation to fulfill needs of growth
TimTec Key Contacts
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Dr. Murat Niyazymbetov - President and CEO
B.S., Mendeleev University, Ph. D., Zelinsky Institute. Worked at Zelinsky Institute of
Organic Chemistry, University of Delaware, Electrosynthesis Company; more than 70
scientific publications.
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Ms. Kay Denisova - Marketing and Bus. Dev., TimTec Products and Services
Consulting. Kay@timtec.net, 1 302 292 8500 x 202
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Dr. Robert J. Chorvat - Medicinal Chemistry Business Development, Consulting. 15
Years DuPont Pharmaceuticals; 18 Years Searle/Pharmacia; 40 publications, 36 US
patents.
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Mr. Tim Niazoff - Director, Information Technology, Software Products and
Computational Services Consulting.
Tim@timtec.net, 1 302 292 8500 x 203
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Mr. Olga Niazoff – VP Finance and Accounting. Olga@timtec.net, 1 302 292 8500 x
204
TimTec Products
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Compound libraries
 General screening
 Targeted
 Diversity
 Template-based
 Privileged structure
 Custom Libraries
Individual compounds
Natural Products
 Pure individual compounds
 Plant extracts
 Semi-natural and Derivatives
Building blocks and intermediates
TimTec Database Accessibility
ACD Database
and others
TimTec Database
Over 5 Million
compounds
Commercial Vendors
Non-exclusive chemists
throughout Europe/Asia
TimTec-exclusive
Chemists throughout
Europe/Asia
Compounds characteristics
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Individually synthesized
Purity - at least 90%, average 95%
NMR (300 MHz or higher) and MS
Possess drug-like properties
Molecular Weight 160 - 600
No reactive groups
No heavy metals
Available in vials and/or 96/384-well plates
Lipinski Rule of Five
Distribution
•Molecular mass not greater than 500
•LogP not greater than 5
•No more than 5 hydrogen bond donors
•No more than 10 hydrogen bond acceptors
Lipinski Rule of Five Distribution
1
2
6
1
2
3
4
91
Molecular Weight Distribution
Molecular Weight Distribution
0.7
Percent of Compounds
0.6
0.5
0.4
0.3
0.2
0.1
0
50
205
305
405
505
Molecular Weight
605
708
877
Libraries Overview
TimTec libraries are characterized according to the following features
that may overlap from collection to collection:
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General screening collections, which would include specifically druglike and generally diverse selections
Targeted, specialty compound collections, ActiTarg Series, template
based, etc.
Nature Inspired: pure natural material or natural product derivatives
and plant extracts
Different size: There are collections of 5,000cmpds, 10,000cmpds,
25,000cmpds, 50,000cmpd, or even 75-100,000cmpds. The latter
would be grand ActiMol collection, our primary stock
Custom: collections selected based on suggested criteria
Formatting options: compounds in dry form or in solutions
Diversity Libraries
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A selection of compounds from currently available stock
that represents the greatest chemical diversity for a
specific number of compounds from that library
Proprietary software is used for these selections
Available Diversity Libraries:
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ActiGlobe 50K
ActiProbe 25K, 10K
ApexScreen 5040
RareCSC (under dev.)
MyriaScreen (Sigma-Aldrich)
MaxiVerse (BIOMOL)
ActiGlobe-50K
The grand diversity collection of 50,000 compounds has been
assembled from world wide sources numbering over 2,000,000
compounds-candidates. The collection has molecules
representing the chemical diversity of screening samples
produced by labs and research centers throughout the world.
In addition to adherence to Lipinski parameters, dozens of
advanced filters have eliminated undesirable atoms, functionality
and fragments creating a library that will provide exceptionally
good chemical starting points for hit and ADMET optimization.
Due to large file size, ActiGlobe-50K database is available on
request for online download. Please call 1 302 292 8500 x 203 or
e-mail at tim@timtec.net
ActiProbe-10K and 25K
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Screening sets of 10,000 and 25,000 compounds respectively
originated from ActiGlobe-50K library. Both collections were selected
through Jarvis-Patrick clustering. The overlap between ActiProbe-10K
and ActiProbe-25K is about 4,500 compounds. Jarvis-Patrick clustering
permits sampling of large library pools through selection of molecules
that are representative of a group (cluster) within this library.
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Molecular characterization is based on 2D fragment descriptors
consisting of a central atom and neighboring atoms connected to it
within a predefined sphere size -- bonds between central and edge
atoms. Groups of molecules are based on the structural similarity of
fingerprints (bit strings of these fragments), and the centroid has the
highest degree of similarity to other members of a cluster. Chemically
unique compounds (singletons) with low similarity to other members of
the collection are also identified. Sampling libraries are created from
centroid and singleton selection along with augmentation with other
members from the largest groups.
MyriaScreen
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Superior structural diversity - Distinct drug-like properties
MyriaScreen was created by combining medicinal chemistry expertise and decades of experience in
compound acquisition from diverse sources. TimTec’s proprietary software was used to filter a pool of
over 300,000 TimTec and Sigma-Aldrich compounds on the basis of diversity. Additional filters were set to
consider MW (>225 and <600), cLogP, H-acceptor, H-donors, and rotatable bonds. Medicinal chemistry
specialists refined the selection with great personal attention to remove compounds that were overly
represented or not well suited for medicinal chemistry follow-up. MyriaScreen is rich in chemotypes and a
valuable source of screening compounds for lead discovery.
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Ready-to-use format - High purity - Efficient re-supply
MyriaScreen is pre-plated for your convenience, 0.5 mg in 250 µL of DMSO per well. The compounds have
an average purity > 95% with nothing below 90%. Should you require more material for follow-up, resupply or re-synthesis is available. Although MyriaScreen is designed for use as a complete set, there are
two alternative options to fit your purchasing needs. Compounds can be purchased as individual plates
or cherry-picked and plated on a custom basis.
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Formatting Options Available:
The collection is pre-plated in 96-well plates and is available on request.
There are 10,000 compounds, 0.5mg or 0.25mg per sample in DMSO solution.
0.5 mg in 250 mcL of DMSO is priced at $40,000.00
0.25mg in 125 mcL of DMSO solution is $24,500.00
0.05mg in 50 mcL of DMSO solution is $12,500.00
In pre-plated sets we have 1 and 12th columns empty.
Diversity Set
It is our most popular competitively priced collection of 10,000 most diverse
compounds selected from TimTec stock of over 120,000 compounds.
Diversity Set is a superior collection in terms of diverse selection of
singletons identified within variety of chemo types in TimTec stock:
2micromol or 1mg samples size in dry form is $53,000.00
5micromol or 2mg sample size in dry form is $64,750.00
0.5mg sample size is $31,000.00
1mg samples size is $47,000.00
On your request we can dissolve compounds in DMSO.
Lead time applies.
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ActiProbe10K, Diversity Set, and MyriaSreen Collection do not overlap in compound
selection. Diversity Set is primarily diverse selection from our stock, variety of
chemotypes is above all in focus. ActiProbe10K as entire collection strictly adheres
to Lipinski rule of five, drug-likeness is in focus.
ApexScreen 5040
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ApexScreen is a collection of 5,040 compounds that were selected to represent the diversity of TimTec
stock of over 120,000 compounds in a smaller format as opposed to larger general screening collections.
ApexScreen in a variety of formatting options tailored to customer requirements is a perfect collection to
jump-start any screening project.
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ApexScreen was created with assistance of TimTec's Diversity Analysis Software that allows the assembly of
libraries with maximized chemical diversity from databases of compounds that are currently available from
TimTecUS and/or overseas stock. Diversity libraries can be further filtered to include molecules that fall within
designated MW, cLogP and Lipinski Rule parameters. TimTec can also provide a selection of compounds from its
databases which will include only those compounds that will contribute to the diversity of an existing customer
library.
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In addition to diverse selection of compounds that represent variety of chemotypes in TimTec general stock
collection, ApexScreen includes a number of pure natural compounds from TimTec Natural Product Library to suit
current trends in screening.
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ApexScreen is a perfect collection for starting any screening project and a valuable addition to any existing
compound library:
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Various formatting option in terms of sample size or concentration are available:
5040 compounds:
0.5mg dry form, $16,800.00, Pre-plated in 96 well plates with removable tubes, rows 1&12th are empty.
0.25mg in DMSO, $11,500.00
0.1mg in DMSO, $8,600.00
Targeted Libraries
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Molecules with molecular scaffolds found in
agents reported in the technical/patent
literature with the following biological
properties:
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Kinase modulation
GPCR binding
Protease inhibition
K-Channel Modulation
Anti-Infectives
NP Scaffold for a Series of
Inhibitors in the Kinase Family
H. Waldmann et al.,
J. Med. Chem., 46, 2917 (2003).
An example: Comprising Targeted Library: ActiTarg-Series
A compound library developed around nakijiquinones, natural inhibitors of the
receptor tyrosine kinase called Her-2/Neu, produced analogs that inhibit two other
receptor tyrosine kinases, VEGFR-3 and Tie-2.
ActiTarg Series
Targeted Libraries
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Our Kinase library, ActiTarg-K, includes over 6,600 drug-like compounds with low molecular
weight that have the ability to inhibit protein kinases. This diverse kinase collection includes
samples-analogs with chemical lattices that match the chemical lattices found in compounds
with already tested kinase activities, which were reported in scientific literature.
You can see the table of kinase and lattice types at:
http://www.timtec.net/actitarg-k-kinase-modulators.html
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GPCR ligands library, ActiTarg-G, currently has 2900 compounds.
These agents possess chemical lattices present in compound types reported in the patent or
chemical literature to have various kinase inhibitory activities, as described on our web site:
http://www.timtec.net/actitarg-g-gpcr-ligands.html
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To meet the interest and needs of investigators who are trying to identify low molecular weight,
drug-like molecules with the ability to inhibit various proteases, TimTec has assembled a library
of compounds with potential protease inhibitory activity, ActiTarg-P. These are about 2,000
compounds in the collection:
http://www.timtec.net/actitarg-p-protease-inhibitors.html
Potassium Channel Modulators, over 800 cmpds:
http://www.timtec.net/potassium-channel-modulators.html
ActiTarg-S,
Serine Proteinase Inhibitors Library
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Serine Proteinase Inhibitors Library collection includes analogs to a group of
serine proteinase inhibitors (serpins) that are known to be similar in amino acid
sequence and mechanism of inhibition, yet differentiate in their specificity toward
proteolytic enzymes as it is reported in technical literature.
For instance, the groups of known serpins among others include: alpha 1antitrypsin, angiotensinogen, ovalbumin, antiplasmin, alpha 1-antichymotrypsin,
thyroxine-binding protein, complement 1 inactivators, antithrombin III, heparin
cofactor II, plasminogen inactivators, gene Y protein, placental plasminogen
activator inhibitor.
TimTec collection currently includes about 450 close analogs to known serpins.
Entire collection in 1mg is $28.00 per compound.
We may also select top diversity compounds and arrange them into plates: 80
compounds in 0.5mg size plated in 96-well plates with removable tubes,
columns 1 & 12 left empty:
3 plates, 240cmpds is $4,560.00
4 plates, 320cmpds is $5,920.00
5 plates, 400cmpds is $7,300.00
Fragment-Based Library
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Low molecular weight
Low binding affinity to a drug target
High solubility
clogP <= 3
Rotable bonds <=5
HBA <=3 and HBD<=3
Privileged Structure Library
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Evaluation of the structures of pharmaceuticals and
agents with good pharmacological activity led to
identification of molecular substructures frequently
associated with a higher level of biological activity.
These motifs were given the "privileged" label when they
were found to be present in molecules that were active
at two or more different receptors.
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Aza-(and diaza-)biphenyls
Benzhydryl compounds
Biphenyls
Dihydropyridines
Anilino-pyridine, pyrimidine, or triazines
Phenylpiperazines
Flavonoids
Natural Product Library
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Diversity by nature
Purity by science
Value by design
Natural Product Library now includes 480 pure individual natural compounds:
From Rediscovering Natural Products article published in Chemical and Engeneering News, why the interest
in natural compounds is increasing:
1) Combinatorial chemistry's promise to fill drug development pipelines with de novo synthetic smallmolecule drug candidates is unfulfilled
2) The practical difficulties of natural products drug discovery are being overcome by advances in
separation technologies and in the speed and sensitivity of structure elucidation
3) A compelling case is being made for the intrinsic utility of natural products as sources of drug
leads.
TimTec has assembled a library of natural products and natural
product-derived compound that provide a broad selection of molecular
frameworks that probe chemical diversity space.
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Solids or freshly prepared DMSO solutions:
0.5mg set is $5,500.00
1mg set is $7,850.00
2mg set is $11,450.00
3mg/$14,950.00
0.05mg in 25 microliters of DMSO is $ 1,750.00
0.1 mg in 50 microliters of DMSO is $2,750.00
0.25 mg in 125 microliters of DMOS is $3,975.00
0.5mg in 250 microliters of DMSO is $5,500.00
Natural Product Derivatives
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Several thousand NP-derived compounds are available
in stock
A selection of about 4000 compounds has been
assembled to provide a representation of the diversity of
this collection
Price depends on the number of compounds selected
and a sample size. Please inquire a quote.
Plant Extracts
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About 9000 cataloged plants from various
regions of the former USSR are available for
collection
About 2500 dried plant species are in stock
Extracts are available on large scale
Fractionation and active component
identification services are possible
Custom Library
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TimTec can comprise compound collection of
different size (from few to thousands of compounds)
utilizing proprietary software based on variety of
custom criteria: structure similarity search, presence
of a particular fragment/s, defined MW, clogP,
number of HBA and HBD, Lipinski Rule, Rule of 3,
etc.
TimTec can also provide a selection of compounds
from its databases which will include only those
compounds that will contribute to the diversity of an
existing customer library. We will do database
comparison and diversity analysis.
Please contact us to discuss customization options.
Additional Notes
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Price on compound libraries and custom selected collections including
cherry-picking would depend on the number of compounds selected
and a sample size.
Custom formatting options are available for all of our libraries. Please
refer to the compound management/handling section of this
presentation.
Prices do not include shipping and cost of custom containers
All compounds we have are stored in dry form and can be freshly
prepared in DMSO.
Purity of compounds in our collections, on average is >/= 95% as
determined by high-field 1H-NMR and/or MS. Overall purity is at least
90%.
Compounds are available for re-supply from stock or after re-synthesis
depending on amounts required. Exact amount available for re-supply
will be confirmed at the time of re-order.
TimTec does not hold any IP rights on compounds we sell. Once a hit is
identified it is yours for further development.
TimTec Services
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Compound Management
Consolidated Compound Procurement
Database management
Computational Services
Custom Synthesis
Analytical
Delaware Technology Park
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Large scale project support
Sample Handling Services
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Custom weighing in dry form or freshly prepared in DMSO
Preparation of storage, master and daughter (96-384 well) plates
Barcode labeling using chemically resistant labels
Conversion of existing libraries into HTS format
Freezer storage of dissolved compounds and overnight shipment under dry ice
Delivery of vials in 96-divider boxes
Consolidated Compound
Acquisition
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Multi-source database mining
Single point-of-service ordering
Preparation of appropriately formatted plates
Uniform database processing
Database management
Possible vendor-to-vendor discounts
Sample Packaging
Analytical Services
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LC/MS at TimTec location
LC/GC/MS and HPLC: Currently partnering with
StereoChemicals in Delaware.
500 MHz instruments: available in US (Ohio State
University) to spot-check samples as needed
High-throughput NMR: a high capacity network
(Moscow) of six instruments, 300 to 500 MHz,
produces spectra in electronic (FID) and/or hard
copy files
Computational Services
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Vendor Database Acquisition and Management
(e.g., duplication and availability determination)
Functional Group and Fragment Filtration
Lipinski Parameter Assessment
Library Comparisons (in-house vs. vendor)
Database Clustering
Database Comparison and Sorting by Diversity
Prediction of lipophilicity (LogP and LogD)
Diversity Analysis of an External Library
compared to an In-house Screening Collection
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Size of in-house library: 561,633 compounds
Size of vendor library: 133,622 compounds
Duplicates identified: 6810 compounds
Number of compounds that will maximize diversity of collection: ~65,000
TimTec Clients
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TimTec has served more than 700 pharmaceutical,
biotech and academic clients.
To name a few:
Aldrich
Anadys
Aventis
AstraZeneca
Boehringer
Cetek
Dow Agro
DuPont
Eli Lilly
Evotec
Ferring
BMS
Glaxo
Amgen
NIH
Genome Therapeutics
Harvard Med
Kanto Chemicals
Mercury Therapeutics
Millennium
Novartis Pharma
Pfizer
Procter & Gamble
Schering – Plough
Serono
Syngenta
Scripps REs Inst
Sepracor
UCB
Unilever
Contact TimTec
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For more information please visit
www.timtec.net
Contact: 1-800-574-7391; 1-302-292-8500
Email: info@timtec.net