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Development of transporter targeted platinum drugs for neuroblastoma

Award Information
Agency: Department of Health and Human Services
Branch: National Institutes of Health
Contract: 1R43CA174132-01
Agency Tracking Number: R43CA174132
Amount: $172,738.00
Phase: Phase I
Program: SBIR
Solicitation Topic Code: NCI
Solicitation Number: PA12-088
Solicitation Year: 2012
Award Year: 2012
Award Start Date (Proposal Award Date): N/A
Award End Date (Contract End Date): N/A
Small Business Information
ATHERTON, CA 94027-3017
United States
DUNS: 78401096
HUBZone Owned: No
Woman Owned: No
Socially and Economically Disadvantaged: No
Principal Investigator
 (650) 361-1192
Business Contact
Phone: (650) 361-1192
Research Institution

DESCRIPTION (provided by applicant): Neuroblastoma (NB) is the most common solid tumor in children. Cisplatin, a first generation platinum analog, is first-line therapy in the treatment f NB and together with other drugs can result in cures of the diseasein about 50% of children. Unfortunately, cisplatin is highly toxic and causes irreversible kidney damage and hearing loss. Cisplatin induced hearing loss is especially devastating in children because it results in lifelong learning difficulties. Moreover,the toxicities are dose-limiting. That is, high dose cisplatin, whch may be curative, cannot be administered. Neuroblastoma has a high level of expression of the norepinephrine transporter (NET), an influx transporter responsible for accumulating norepinephrine in neuroendocrine cells. Designing therapeutic agents to be transported by NET therefore confers a promising approach to achieve targeted delivery of cytotoxic agents in tumor cells, which could result in higher activity and reduced toxicity to other tissues. In preliminary studies we designed, synthesized and tested platinum analogs to target NET. We identified two lead compounds, which have enhanced potencies in NB cell lines expressing higher NET expression levels. The overall goal of our studiesis to perform pharmacokinetics and dose-limiting toxicity studies of these compounds relative to cisplatin in mice. In addition, the goal o this study is to identify a maximum tolerated dose (MTD), which is the highest dose that does not cause any measurable toxicity in the mice. These studies are crucial for the next phase in determining the efficacy of the lead NET targeted compounds in neuroblastoma mouse model. The proposed studies will confer high commercialization potential for the two lead compoundssince both analogs would be poised for critical Investigational New Drug (IND) enabling studies PUBLIC HEALTH RELEVANCE: The proposed research will lead to the development of a new medicine for the treatment of a life- threatening solid tumor inchildren, neuroblastoma. If successful, this research will lead to the development of a highly effective drug with fewer side effects and in particular, a drug that will not cause deafness, a common side effect of current therapies. The development of thismedication will make an enormous contribution to the treatment of the most common solid tumor in children

* Information listed above is at the time of submission. *

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