Chemoprotectants for Head-Neck Therapeutics

Award Information
Agency: Department of Health and Human Services
Branch: N/A
Contract: 2R44CA140166-02A1
Agency Tracking Number: R44CA140166
Amount: $1,402,563.00
Phase: Phase II
Program: SBIR
Awards Year: 2011
Solicitation Year: 2011
Solicitation Topic Code: NCI
Solicitation Number: PA10-050
Small Business Information
REACTION BIOLOGY CORPORATION
ONE GREAT VALLEY PARKWAY, MALVERN, PA, -
DUNS: 611741799
HUBZone Owned: N
Woman Owned: N
Socially and Economically Disadvantaged: N
Principal Investigator
 HAICHING MA
 (610) 722-0247
 haiching@reactionbiology.com
Business Contact
 HAICHING MA
Phone: (610) 722-0247
Email: haiching@reactionbiology.com
Research Institution
 Stub
Abstract
DESCRIPTION (provided by applicant): Chemoprotectants for Head-Neck Therapeutics Oral mucositis occurs as a major dose-limiting and complicating side effect of chemotherapy, radiotherapy, or combined chemo/radiotherapy. It is considered the most significant complication of head and neck cancer therapy. Oral mucositis is accompanied by tremendous pain and can cause life threatening complications. Dysfunction in swallowing following laryngeal cancer therapy can be particularly debilitating. The development ofchemoprotectants is the central goal of this proposal. In preliminary studies, Reaction Biology Corporation has discovered selective, reversible, small molecule caspase inhibitors, which have multiple advantages compared to the compounds in the clinical trials. For example, caspase inhibitors from many pharmaceutical companies' drug discovery programs have one of more of the following characteristics: irreversible, peptide-mimic, Pan-caspase inhibitor. In Phase I studies, these compounds are very active incell based assays, demonstrated significant cell death prevention activities in chemical and radiation induced cell death in normal cell lines. In this Phase II application, we will continue to improve these inhibitors in potency and efficacy in cell based assays and DMPK profiles, to look for the final lead(s) in animal model tests. In this new proposal, the key aims are: 1) Structure-Activity Relationship (SAR) studies to improve caspase inhibitors' potency; 2) Define caspase inhibitors' treatment conditions in vitro in conjugation with chemotherapy and radiation treatments; 3) Test caspase inhibitors' tissue penetration and efficacy in protecting oral mucous cells from radiation therapy in 3D oral mucosa model. PUBLIC HEALTH RELEVANCE: Chemoprotectants for Head-Neck Therapeutics Oral mucositis occurs as a major dose-limiting and complicating side effect of chemotherapy, radiotherapy, or combined chemo/radiotherapy. It is considered the most significant complication of head and neck cancer therapy.Oral mucositis is accompanied by tremendous pain and can cause life threatening complications. Dysfunction in swallowing following laryngeal cancer therapy can be particularly debilitating. Even though apoptosis is considered the central theme in oral mucositis, little work with caspase inhibitors has been conducted to date. Reaction Biology Corp. has discovered a few novel, potent and selective caspase inhibitors and would like to evaluate their cell death protection activities in chemotherapy and radiation induced apoptosis assays. Additional SAR studies will improve the potency of these compounds, and studies in 3D oral mucosa models will further reveal tissue penetration and cell protective properties of caspase inhibitors without testing in vivo animalmodel, which will help to eliminate toxic and ineffective compounds in early stage, and reducing the number of studies in animal models in the future.

* information listed above is at the time of submission.

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