Technologies - TTP

Overview - Available Technologies

BI-78D3 binding to ERK2 (PDB 4ERK); text reads T157, T158, C159, H123

TTP offers technologies in the following areas:


Please view their respective sections below for additional details.

Chemical Library

TTP offers unique and assorted compound collections to fit diverse scopes of targets and research goals.

Currently ~83,000 compounds acquired from various resources are available that include bioactive compounds with defined biologic activity, purified natural products, chemical fragments, structurally diverse small molecules and FDA-approved and investigational drugs.

Area of Targets: inhibitors, activators, antagonists, and agonists focused on targets in the area of, but not limited to, oncology, infectious disease, diabetes, epigenetics, ion-channel ligands, GPCRs, proteases, and over 20 signaling pathways such as, PI3K/Akt/mTOR, and MAPK pathways.

The core increases the uniqueness of its collection by acquiring new compounds from academic laboratories (e.g. Synthetic compounds from U of Kansas), commercial vendors, research institutes (e.g. Scaffold Ranking library from Torrey Pines Institute), and DNA-coded libraries from Baylor as well as pharmaceutical companies (e.g. Published Kinase Inhibitor Sets from SGC-UNC). TTP also offers uniquely assembled kinase focused compounds.

Kinase–focused Compounds Collection
  • The most extensive in the State, thoughtfully assembled, based on our in-depth experience on protein kinase enzymology.
  • Over 600 compounds assembled from various commercial vendors targeting a broad spectrum of kinases (over 100 kinases).
  • Serves as an excellent starting point for medicinal chemistry progression due to its potential to provide rapid access to target-directed inhibitors for orphan kinases at low nanomolar potency.
  • Serves as a useful probe library to identify potential signaling pathways that support critical cancer phenotypes and metastasis.
Representative Collections
  • Fsp3 Enriched compounds (LifeChemicals)
  • Diversity sets (Chemdiv, Chembridge, Maybridge)
  • Fragment sets (Chemdiv, Chembridge; brominate-specific, halopyridine-specific)
  • Natural products and Natural like collection (MicroSource, NIH, NCC, LifeChemicals)
  • Approved and biologically active compounds (custom collection, NIH, and NCC)
  • Kinase targeted drugs and bioactive compounds (custom collection)
TTP Compounds Brochure

Download the TTP Compounds brochure

Instruments

TTP is fully equipped with high-end instruments and has continuously upgraded instruments to keep them in top operating condition.  

TTP has managed instrumentation in four systems (Detection, Liquid handling, Synthesis, and Tissue culture) along with basic laboratory equipment (Miscellaneous) and an on-line reservation (web-based instrument scheduler).

Our goal is to equip with machines that cover as broad of a range of technologies as possible without sacrificing sensitivity or throughput, so we can best support flexible and affordable screening campaigns.

Detection

Our plate readers are applicable for various applications such as, but not limited to, drug discovery, enzyme kinetics, cell proliferation, cytotoxicity, drug absorption and metabolism, biologics drug discovery and development, nucleic acid quantification, protein quantification, biomarker quantification, ELISAs, and genetics analysis.

Please refer to the plate reader chart for quick comparison and selection.

Neo2 Plate reader (Agilent)  
Both filter-& monochromator based plate reader specific for assay development or low throughput screen, integrated plate stacker holding 20 plates and dispenser. Included reagent dispenser, environment control, and bar-code reader. Integrated plate stacker holding 20 plates. 

Synergy H4 Plate reader (Agilent) Both filter-& monochromator based plate reader specific for assay development or low throughput screen, integrated plate stacker holding 20 plates. 

Cytation 5 cell imaging multi-mode reader (Agilent) Specific for dual cell imaging and multi-mode microplate reading on fluorescence, bright field, color bright field and phase contrast microscopy 
Equipped with CO2/O2control and incubation (rt—60⁰C). Learn more about Cytation’s capability.

FlexStation 3 Multi-Mode Microplate Reader (Molecular Device) A benchtop system integrates multi-mode microplate optics with precision, programmable liquid handling for perfect timing. Specific for fast kinetics assay development equipped with a temperature control up to 45⁰C).

Other Detection Systems: 
Incucyte® S3 Live Cell Analysis System (Sartorius) A compact dual fluorescent and HD-phase contrast imaging microscope housed in a standard incubator for real time quantitative live-cell imaging and analysis. Equipped with different microscope objectives (4x, 10x, 20x), reads up to 6 microtiter plates, and acquires >2000 images per hour. Applications for cell health & viability (apoptosis, proliferation, cytotoxicity, tumor spheroids), live cell assays (angiogenesis, cell migration and invasion, immune cell clustering and proliferation), cell monitoring and workflow (cell culture QC, dilution cloning, reporter genes, stem cell monitoring and reprogramming, transfection efficiency) 

J-815 CD spectrometer (Jasco) Specific for optically active chemicals and secondary structure analysis of biological molecules equipped with an autosampling (2 x 96 well plates), temp control (6—110⁰C) for thermal melting, wavelength range of 163-900 nm, & 6 cell simultaneous analysis. Specific applications are protein conformational studies, quantitative analysis of pharmaceuticals, formulation studies, protein folding studies, DNA/RNA interactions. Learn more about CD technology. 
Comprehensive tools for data analysis can be found at  http://dichroweb.cryst.bbk.ac.uk/html/home.shtml. 

Cary 4000 UV-Vis (Agilent) High performance UV-Vis spectrometer, specific for Tm analysis of biological molecules equipped with an 6×6 peltier cell holder, temp control (-10—100⁰C), wavelength range of 175-900 nm. Measure beyond 8.0 absorbance.

Biacore S200 (Cytiva) Most sensitive SPR instrument offering increased productivity in LMW/fragment drug discovery. 384 single-concentration fragment binding data can be acquired in less than 16 h. Equipped with 4 channels and capable of measurement of affinity, kinetics, concentration, and specificity of biological interactions between a ligand and an analyte in a real time format. Learn more about SPR technology.

QuantStudio 7 Pro RT-PCR (ThermoFisher) Real-time PCR system equipped with interchangeable 96-well, 384-well, and Taqman Array card blocks. Multiplexing up to 6 targets, 10 order of dynamic range, 1.5x resolution, compatible with diverse dyes, temperature ranges between 4-99.9°C, 21 filter or color combination, 6 independent temperature zones (96-well blocks). Specific for protein thermal shift (DSF), single-nucleotide polymorphism (SNP) genotyping, gene expression, high resolution melting, etc. Learn more about DSF technology.

Liquid Handling

Echo® 550 Liquid Handler (Beckman Coulter) Main screening liquid handler used for reagent or library transfer for assay, library reformatting, serial dilution, or cherry pick. 

Janus Automated Workstation (Revvity) Main screening liquid handler used for reagent or library transfer for assay, library reformatting, serial dilution, or cherry pick.

Microflo Select (Agilent) Specific for rapid bulk liquid dispensing (1 uL ~1 mL) equipped with an integrated plate stacker up to 30 plates.

Multiflo Fx multi-mode Dispenser (Agilent) Specific for rapid bulk liquid dispensing (1 uL ~1 mL) equipped with an integrated plate stacker up to 30 plates and parallel dispensing technology.

EL405lx Plate washer (Agilent) Versatile application from basic ELISA to sensitive cell or bead washing with rapid wash of 96– or 384 microwell plates.

Chemoinformatics

Computing cluster: 500-core Dell Linux cluster with Gigabit network and a 16 TB disk storage, 12 GTX1070 GPUs, Lonestar 5 (available from TACC, 30048 compute cores, 5 PB disk storage, 40 GPUs)

High-end Dell graphics workstation

Software: Datawarrior, Chemaxon, Daylight Reaction Toolkit, ROCS and EON (OpenEye), GOLD (CCDC), AMBER, GROAMCS, TINKER, OpenMM, Pymol, VMD, Chimera

Tissue Culture

Forma 3110 CO2 Incubator (37⁰C/5% CO2)
Leica DMi1 microscope (4x, 10x, 20x)
Biosafety hood, centrifuge, & water bath

Miscellaneous

PlateLoc Plate Sealers
Centrifuge 5810R (-4°C~40°C, ~14,000 rpm)
Bar Code Printer
Analytical Balance (XP205, Mettler Toledo)

Instrument Reservation

Trained and approved users can reserve instruments in advance, and usage fees will be billed based on reservation records.

Visit the reservation page to make a reservation.

For training or inquiries for instrument access, please contact Core Director, Eun Jeong Cho.

TTP Instrument Brochure

Download the TTP Instrument brochure

Data Analysis and Storage

TTP partnered with Collaborative Drug Discovery (CDD) for Data Base access, a web-based system that organizes preclinical research data to facilitate compound/assay management, data analysis, mining, & clustering.