molecular targets development program, ccr, nci
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Molecular Targets Development Molecular Targets Development Program, CCR, NCIProgram, CCR, NCI
OMe
N
O
O
O
OH2O3PO
HO
Advanced BiomedicalAdvanced BiomedicalTechnologiesTechnologies
CCRClinical
Program
Molecular Targets & Molecular Oncology
Genetics & Genomics
Imaging & Biomarkers
IntegratedSystemsBiology
Immunology,Immunotherapy &
Immunoprophylaxis
HIV/AIDS
Intra
mura
l/Extra
mura
l
Translational Research at the CCR
Center for Cancer Research
• 15 clinical branches
• 38 basic sciences laboratories
• > 330 principal investigators
A549SNB19
MTDP
HTS Data
MTDP Mission
Lab Bench Data
MTDP Mission
MTDP
• Collaborate with CCR investigators to develop and apply molecular target-specific assays
• Screen the NCI natural products repository and other sources of chemical diversity
• Identify and characterize target-specific compounds• Provide active compounds to collaborating labs for use as
bioprobes
Target Consortium
Molecular
Target/Pathway
Staff Scientists
Lab ChiefsPostdoctoral Fellows
PIs
Proposal
Initial Feasibility
• Quality control of reagents and cell lines– Reagent stability– Reagent specificity and binding characteristics– Cellular growth characteristics
• Time frame of assay– Stable end point
• Signal to noise ratio• Availability of appropriate controls• Availability of required equipment• Availability of sufficient reagents
Priority Areas
• Screening Platforms
• Natural Products
• Protein Chemistry and Molecular Biology
• Libraries
• Imaging
• Information Technology
Screening Platforms
Enzymatic- FRET
Protein-Protein Interactions- Time-Resolved Fluorrescence- Electrochemiluminescence
Cell-based- Colorimetric- Fluorometric- Luminescent
Cell-Imaging- GFP Translocation- GFP Expression
Project Rationale Project Rationale
MDM2/ubiquitination
p53 induced apoptosis
gp78 ER stress response
RNaseH HIV inhibition E2A/SCL aberrant gene expression
ABCG2 multi-drug transport
RNAi/IGFR resistance to apoptosis
cKIT signal transduction
Cripto 1 cell adhesion
HDAC/DNMT epigenetic control Polo-like
kinase 1
cell cycle control
HIF-2 hypoxia response Smad 3 signal transduction
ER breast cancer cMet signal transduction
AP1 chemo-prevention
Ezrin cytoskeletal reorganization
TRAIL apoptotic synergy
MTDP Ongoing Projects
Name of Library Source Sample Type # Samples
MTDP Isolated Compounds MTDP Pure NP 322Pure Natural Products DTP Pure NP 4486Korean Pure NPs Chungnam National University Pure NP 174Pure Natural Products BioMol Pure NP 231Actinomycete Products Ecopia Biosciences Pure NP 16Fungal Products University of Iowa Pure NP 168 5397
Natural Product Extracts DTP NP Extract 133154Iowa Extracts University of Iowa/DTP NP Extract 1884Korean Extracts Chungnam National University NP Extract 3423Cytotox Deck DTP NP Extract 1840Extract Test Plates MTDP/DTP NP Extract 168Endangered Plants Cincinnatti Zoo NP Extract 8Prefractionation Library MTDP/DTP Partially purified extract 10000 150477
CCR Compounds CCR PIs Synthetic 129BU Compounds Boston University CMLD Synthetic 1498Pitt Compounds University of Pittsburgh CMLD Synthetic 1398Kansas Compounds University of Kansas CMLD Synthetic 479Berkeley Compounds University of Cal., Berkeley Synthetic 17Rome Compounds University of Roma Synthetic 1900Morocco Compounds University of Morocco Synthetic 123UMBC Compounds UMBC Synthetic 318ICCB Bioactives BioMol Synthetic 480Kinase Library PKI Synthetic 80Structural Diversity Set DTP Synthetic 1929Mechanistic Diversity Set DTP Synthetic 879Challenge Set DTP Synthetic 49LOPAC1280 Sigma Synthetic 1280 10559
Totals 166433
Current Libraries for Screening
NCI’s Natural Products Collections and NCI’s Natural Products Collections and Extract RepositoryExtract Repository
Terrestrial Plants-Tropical and Subtropical
Marine Invertebrates and Algae-Indopacific-Caribbean
Selected Microbial Isolates-Cyanobacteria-Fungi
> 65,000 Organisms
> 170,000 Individual Extracts-Organic Solvent Extracts-Aqueous Extracts
Collections
Extract Repository