# Presentation: 275168

## Turning Molecules Into Medicines

**Turning Molecules Into Medicines**

## Developmental  Therapeutics Program 2000

- GRANTS & CONTRACTS

-   Molecular Target Drug Discovery for Cancer
-   Flexible System to Advance Innovative Research
- for Cancer Drug Discovery by Small Businesses
-   International Cooperative Biodiversity Groups
-   National Cooperative Drug Discovery Groups
-   Small Business Innovative Research/
- Small Business Technology Transfer

- MTDD
- FLAIR
- ICBG
- NCDDG
- SBIR/STTR

## Facilitating Discovery 
Alliance Seeker
Linking Compounds and Screens
Compound, tumor, biologics libraries
HTS support for Cancer and AIDS
WEB-based tools for Informatics
Target-based in vivo testing

- Facilitating Discovery
- Alliance Seeker
- Linking Compounds and Screens
- Compound, tumor, biologics libraries
- HTS support for Cancer and AIDS
- WEB-based tools for Informatics
- Target-based *in vivo* testing

- Development Services
- RAID Program
- Lead Optimization
- Toxicology
- Pharmacology
- Formulation
- Entry into Clinical Trials Network or Master Drug Files

- Developmental  Therapeutics Program 2000

## Developmental  Therapeutics Program 2000

- SYNTHETIC REPOSITORY

-   Open compounds
- (140,000 samples)
-   Diversity set
- (1,990 samples)
-   Challenge set
- (57 samples)

## Developmental  Therapeutics Program 2000

- RADIOLABELED DRUGS

-   > 100 drugs
-   Free of charge to qualifying researchers
-   Must have valid radioactive materials license

## Developmental  Therapeutics Program 2000

- TUMOR REPOSITORY

*In vivo*-derived tumors
- & *in vitro*-established cell lines

**Tumors from:**
**humans**
**guinea pigs**
**hamsters**
**rabbits **
**mice**
**rats**

- 106 - 107 cells
- ~ 1 cc of culture medium

- $150 for domestic shipments
- $250 for foreign shipments
- $75 each additional vial

## Developmental  Therapeutics Program 2000

- NATURAL PRODUCTS REPOSITORY

- >50,000 plant
- samples

- >10,000 marine
- samples

- aqueous &
- organic
- extracts

- Collected with concern for:
- conservation of biological diversity
- fair & equitable collaboration with
- source countries

## Developmental  Therapeutics Program 2000

- PRECLINICAL REPOSITORY

- Murine Cytokine
- Standards
- Human
- Cytokine Standards

- Bulk Cytokines
- Anti-Murine
- & Anti-Human
- Monoclonal Antibodies

- Growth Factors
- Interferons
- Interleukins

- Human Interleukins
**Antiangiogenic**
**Agents**

## Developmental  Therapeutics Program 2000

**ANIMAL PRODUCTION PROGRAM**

## Developmental  Therapeutics Program 2000

-   Confidentiality agreement available
-   No charge for screening
-   Submit structures for review
-   Supply samples of accepted compounds
-   3 cell line, one dose prescreen

*IN VITRO* SCREENING

- Prescreen actives sent for ......

## Developmental  Therapeutics Program 2000

***IN VITRO***** 60 CELL LINE SCREEN**

- 8 breast
- 2 prostate
- 8 renal
- 6 ovary
- 7 colon
- 6 brain
- 9 lung
- 8 melanoma
- 6 hematopoietic

**60 CELL LINES**

## Developmental  Therapeutics Program 2000

-  of particular cell lines
- as deflection from mean

- COMPARE degree of similarity of new compound
- to standard agents
- Calculate mean GI50,
- TGI, LC50

***COMPARE***
**PATTERN RECOGNITION ALGORITHM**

***1 = identity ; 0 = no correlation***

-   Calculate Pearson correlation coefficient

## Developmental  Therapeutics Program 2000

- rad52

- rad50

**A camptothecin**

**NCI YEAST ANTICANCER DRUG SCREEN**

***The Seattle Project: Dunstan, Lamb, Szankasi, Simon, Friend***

## Developmental  Therapeutics Program 2000

- cultivated & suspended
- flushed into 1mm diameter
- polyvinylidene hollow fibers
- heat sealed at 2cm intervals

- HOLLOW FIBER ASSAY

-   i.p. injection of agent
-   stable endpoint
- MTT assay
-   % net cell growth
- calculated

## Developmental  Therapeutics Program 2000

**Define/optimize dose & schedule**
**Conduct pharmacology studies**
**Bulk substance acquisition**
**Scale-up production**
**Develop suitable formulations**
**Production of dosage forms**

**Stability assurance of dosage forms**
**Range-finding initial toxicology**
**IND-directed toxicology**
**Planning of clinical trials**
**IND filing advice**

## http://dtp.nci.nih.gov

***http://dtp.nci.nih.gov***

## Developmental  Therapeutics Program 2000

**WEB SITE DATA FOR DOWNLOAD**

- Human tumor cell line
-   screen results
- AIDS antiviral screen results
- Chemical structures
- Molecular targets characterized
- NCI60 cancer microarray project

- >31,000 cmpds
- >15,000 extracts
- >32,000 cmpds
- >200,000 cmpds
- >300 targets
- >150 MB data

## Developmental  Therapeutics Program 2000

- NCI60 CANCER MICROARRAY PROJECT

- Gene expression patterns related to tissue of origin of cell lines

## Developmental  Therapeutics Program 2000

- MEASUREMENTS OF
- MOLECULAR TARGETS IN CELL LINES

- Relative Expression
- of EGF Receptor mRNA

## Developmental  Therapeutics Program 2000

**COMING SOON TO DTP’s WEB SITE!**

**ONLINE STRUCTURE SUBMISSIONS**

-   Enter structures of compounds for testing
-   E-mail notification that structures received
-   E-mail notification of selected structures

## Thank You!

- For more information see:
- http://dtp.nci.nih.gov
- Jill Johnson
-   johnsoji@exchange.nih.gov