Program Description
Investigators will conduct preclinical development of several synthetic triterpenoid derivatives of CDDO. Several new synthetic triterpenoid derivatives of CDDO have exhibited activity in various chemopreventive and chemotherapeutic cell culture models. However, these promising pharmacodynamic properties are limited in vivo by suboptimal pharmacokinetic characteristics of these compounds. CDDO will be used as a starting material for new derivatives with improved pharmacokinetic profiles. RAPID support will include bulk synthesis of 2-cyano-3,12-dioxooleana-1,9-dien-28-oic acid (CDDO).

Contact Information
Michael B. Sporn, M.D.
Dartmouth Medical School
Dartmouth, NH
Tel: 603-650-6557
Fax: 603-650-1129

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Program Description
Investigators will conduct preclinical development of a-TEA (2,5,7,8-tetramethyl-2R-(4R', 8R', 12'-trimethyltridecyl)chroman-6-yloxy) acetic acid a novel synthetic derivative of naturally occurring vitamin E (RRR-a-tocopherol). Preliminary studies in mouse mammary cancer models showed that this compound can inhibit tumor growth and metastasis without toxicity. It was proposed that it may be effective in preventing breast cancer recurrence and spread. The initial RAPID support will include:

• Scale up non-GMP synthesis of a-TEA,
• In vivo preclinical efficacy studies, and
• Preclinical genotoxicity studies.

Contact Information
Kimberly Kline, Ph.D. and Bob G. Sanders, Ph.D.
University of Texas at Austin
Austin, TX
Tel: 512-471-8911 (KK)
Tel: 512-471-7441 (BGS)
Fax: 512-232-7040 (KK)
512-232-7040 (BGS)

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Program Description
Investigators will conduct preclinical development of the Glucosinolate of Sulforaphane (Glucoraphanin). Glucosinolates (e.g. glucoraphanin) are stable precursors of isothiocyanates and are naturally occurring substances found in cruciferous vegetables. Glucoraphanin and sulforaphane have been isolated from broccoli and its seeds and sprouts and demonstrated to possess significant anticarcinogenic activity, probably mediated by the induction of Phase 2 drug metabolism enzymes. In addition, they also exhibit strong bactericidal activity against intracellular, extracellular and antibiotic resistant H. pylori. RAPID support will include:

• Process development and scale-up production of high purity glucoraphanin,
• In vivo preclinical efficacy studies, and
• Preclinical toxicology studies.

Contact Information
Paul Talalay, M.D.
Johns Hopkins University School of Medicine
Baltimore, MD
Tel: 410-955-3499
Fax: 410-502-6818

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Program Description
Investigators will conduct preclinical development of SR13668, a new synthetic analog of naturally occurring indole-3-carbinol (I3C). I3C is found in cruciferous vegetables (broccoli, cabbage etc.) and exhibits several chemopreventive activities. SR13668 is a result of lead-based rational drug design using computational modeling to optimize chemopreventive I3C activities and minimize its undesirable characteristics. RAPID support will include:

• Scale up non-GMP synthesis of SR13668 for preclinical studies,
• In vivo preclinical efficacy studies,
• Preclinical toxicology studies, and
• Preclinical pharmacokinetic studies.

Contact Information
Ling Jong, Ph.D.
SRI International
Tel: 650-859-6121
Fax: 650-859-3153

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Program Description
Investigators will conduct preclinical development of Dietary Polyethylene Glycol (PEG). Water-soluble, high molecular weight polymeric polyethylene glycols are used as food additives and gentle laxatives. They are not absorbed from the gastro-intestinal tract and nor are they metabolized by gut microflora. They possess low toxicity and have recently showed chemopreventive activity in carcinogen-induced colon cancer in rats. Supporting scientific documentation will be presented for consideration of a phase 1/2 clinical study with modulation of aberrant crypt foci as the primary endpoint.

Contact Information
Denis E. Corpet, Ph.D.
Universite De Toulouse, France
Tel: 33-561-1939-82
Fax: 33-561-491-263

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Program Description
Investigators will conduct preclinical development of mycochemicals in shiitake mushrooms. Shiitake mushrooms (Lentinus edodes) have been described as having various medicinal properties, including chemopreventive ones. Studies in animal models support anti-cancer activity of Shiitake mycochemicals following oral consumption. RAPID support will include:

• growth and preparation of standardized log-grown Shiitake mushroom preparation;
• determination of dietary levels of mushrooms for subsequent studies;
• development of analytical methods for identification of mushroom mycochemicals;
• bioactivity based assays to identify mycochemicals;
• and correlation of mycochemicals in mushrooms, urine, and serum.

Contact Information
Thomas M. Badger, Ph.D.
University of Arkansas for Medical Sciences
Tel: 501-320-2785
Fax: 501-320-2818

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Program Description
Investigators will conduct preclinical development of a topical niacin prodrug for skin cancer prevention. It has been proposed that a topical application of niacin prodrug will prevent, reverse early signs of skin cancers (actinic keratoses), or inhibit progression to cancer. This agent may exert its effects by stimulation of poly(ADP-ribose) polymerase (PARP-1) activity and leptin and their downstream signaling pathways. RAPID support will include:

• Preclinical toxicology studies,
• Analytical method development,
• Absorption/distribution/metabolism/elimination studies, and
• Animal efficacy studies.

Contact Information
Elaine L. Jacobson, Ph.D.
University of Arizona
College of Pharmacy and Arizona Cancer Center
Tucson, AZ
Tel: 520-626-2272
Fax: 520-626-8567

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Program Description
Investigators will conduct preclinical development of the brown rice constituent tricin as a cancer chemopreventive agent. The flavonoid tricin has been identified as a constituent of brown rice and rice bran. Preliminary studies have demonstrated biological properties in cells in vitro indicative of chemopreventive activity in vivo. RAPID support will include:

• synthesis of bulk tricin.

Contact Information
Andrew J. Gescher, Ph.D., D.Sc.
University Leicester
United Kingdom
Tel: (44) 116 223 1856
Fax: (44) 116 223 1855

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Program Description
Investigators will conduct preclinical and clinical investigation of the safety and tolerability of a human papillomavirus virus-like particle vaccine co-administered in combination with E. coli heat-labile enterotoxin mutant R192G (LTR192G) by oral, intranasal, or transcutaneous routes of immunization. Certain human papillomaviruses cause cervical cancer, which remains a significant source of morbidity and mortality among women worldwide. This project proposes to study the safety and tolerability of a virus-like particle vaccine when co-administered with adjuvant E. coli LTR192G by three alternate routes of delivery (oral, intranasal, or transcutaneous). RAPID support will include production of HPV-16 L1 and E. coli LTR192G for preclinical testing.

Contact Information
Robert C. Rose, Ph.D.
University of Rochester School of Medicine
Rochester, NY
Tel: 716-275-0263
Fax: 716-442-9328

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Program Description
Investigators will conduct preclinical development of 9-cis-UAB30, a nuclear retinoid X selective agonist receptor, for breast cancer chemoprevention. Retinoids that selectively interact with nuclear retinoid X receptors (RXRs) have been shown to be effective in the prevention of mammary cancer either alone or in combination with antiestrogens. 9-cis-UAB30 represents a new class of RXR-selective retinoids and has been shown to be nontoxic and effective in a cancer chemopreventive mammary model. RAPID support will include:

• bulk synthesis and preclinical toxicology studies.

Contact Information
Donald D. Muccio, Ph.D.
University of Alabama
Birmingham, AL
Tel: 205-934-4747
Fax: 205-934-2543

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