Alkylating Vitamin D Derivative

Award Information
Agency: Department of Health and Human Services
Branch: N/A
Contract: 1R41CA126317-01A1
Agency Tracking Number: CA126317
Amount: $258,398.00
Phase: Phase I
Program: STTR
Awards Year: 2007
Solitcitation Year: 2007
Solitcitation Topic Code: N/A
Solitcitation Number: N/A
Small Business Information
APHIOS CORPORATION
APHIOS CORPORATION, 3-E GILL ST, WOBURN, MA, 01801
Duns: 194643722
Hubzone Owned: N
Woman Owned: N
Socially and Economically Disadvantaged: Y
Principal Investigator
 TREVOR CASTOR
 (781) 932-6933
 APHIOS@AOL.COM
Business Contact
 PERCIVAL CASTOR
Phone: (781) 932-6933
Email: tastor@aphios.com
Research Institution
 BOSTON UNIVERSITY
 BOSTON UNIVERSITY
881 COMMONWEALTH AVENUE
BOSTON, MA, 2215
 Nonprofit college or university
Abstract
DESCRIPTION (provided by applicant): Prostate cancer is the most prevalent cancer among men; and the second leading cause of cancer death among men in the US. There are currently no approved therapies for hormone-refractory prostate cancer. Epidemiological studies have demonstrated a strong relationship between incidence of and mortality from various cancers including prostate cancer, exposure to the sun and cutaneous synthesis of vitamin D. The biologically active form of vitamin D has been shown to have strong antiproliferative effects in cancer cells, but it is highly toxic at therapeutic doses. In vitro tests of 1,25-dihydroxyvitamin D3-3-bromoacetate (1,25(OH)2D3-3-BE), an analog of vitamin D designed to have increased antiproliferative effects while reducing systemic toxicity through alkylation of vitamin D receptor (VDR) in tumor cells, have shown that this compound has strong growth-inhibitory and apoptosis-inducing properties in hormone-sensitive and hormone- refractory prostate cancer cells. In vitro assays have clearly shown its effectiveness, even when compared to 1,25-dihydroxyvitamin D3, the active form of vitamin D hormone. Furthermore, preliminary in vivo studies showed that 1,25(OH)2D3-3-BE is non-toxic, and it strongly reduces androgen-refractory tumor in a mouse xenograft model. The proposed research in this STTR Phase I application includes formulation of 1,25(OH)2D3-3-BE in nanosomes, determination of the bioavailability and quantification of the drug in formulation, determination of the stability of this compound neat and in its nanosomal preparation in serum and liver homogenate, determination of maximum tolerated dose of the formulated drug in mice, and evaluation of the efficacy of the formulation in reducing prostate tumor in mouse xenograft models. The data generated from the proposed studies will advance the development of this potential therapeutic agent for hormone- sensitive and hormone-refractory prostate cancers at all stages.

* information listed above is at the time of submission.

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