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Alkylating Vitamin D Derivative

Award Information

Agency:
Department of Health and Human Services
Branch:
N/A
Award ID:
85423
Program Year/Program:
2007 / STTR
Agency Tracking Number:
CA126317
Solicitation Year:
N/A
Solicitation Topic Code:
N/A
Solicitation Number:
N/A
Small Business Information
APHIOS CORPORATION
3 E GILL ST WOBURN, MA 01801-1720
View profile »
Woman-Owned: No
Minority-Owned: No
HUBZone-Owned: No
 
Phase 1
Fiscal Year: 2007
Title: Alkylating Vitamin D Derivative
Agency: HHS
Contract: 1R41CA126317-01A1
Award Amount: $258,398.00
 

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 s trong 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 re ducing 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 vitr o 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-refrac tory 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 st ability 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 xeno graft 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.

Principal Investigator:

Trevor P. Castor
7819326933
APHIOS@AOL.COM

Business Contact:

Percival T. Castor
Small Business Information at Submission:

APHIOS CORPORATION
APHIOS CORPORATION 3-E GILL ST WOBURN, MA 01801

EIN/Tax ID: 043205324
DUNS: N/A
Number of Employees: N/A
Woman-Owned: No
Minority-Owned: No
HUBZone-Owned: No
Research Institution Information:
BOSTON UNIVERSITY
BOSTON UNIVERSITY
881 COMMONWEALTH AVENUE
BOSTON, MA 2215
RI Type: Nonprofit college or university