Novel Inhibitors of Pim Protein Kinases

Award Information
Agency: Department of Health and Human Services
Branch: N/A
Contract: 1R41CA135804-01A2
Agency Tracking Number: CA135804
Amount: $257,864.00
Phase: Phase I
Program: STTR
Awards Year: 2009
Solicitation Year: 2009
Solicitation Topic Code: N/A
Solicitation Number: PHS2009-2
Small Business Information
DUNS: 827435749
HUBZone Owned: Y
Woman Owned: N
Socially and Economically Disadvantaged: N
Principal Investigator
 (843) 792-8284
Business Contact
Phone: (843) 791-3420
Research Institution
 Office of Research and Sponsored Programs
19 Hagood Ave., Suite 606
CHARLESTON, SC, 29425 4919
 Nonprofit college or university
DESCRIPTION (provided by applicant): There is a growing body of evidence that implicates the protein kinase Pim-1 as a major driver of prostate cancer progression, and perhaps response to chemotherapy. Pim-1 is overexpressed in early prostate intraepithelial neoplasia and metastatic prostate cancer, and its levels predict response to therapy. Pim-1-overexpressing mouse prostate stem cells demonstrate abnormal growth in 3-D collagen cultures, and develop into PIN when placed under the renal capsule. In Rbnull stem cells, Pim-1 overexpression induces frank neoplasia when grown in the renal capsule model. Pim-1 modulates signaling through the mTOR pathway, providing additional opportunities for targeted cancer therapy. Therefore, the goal of this program is to develop unique inhibitors of Pim-1 that will function, with or without a TOR protein kinase inhibitor such as rapamycin, to treat prostate cancer. We have identified a new chemotype that inhibits Pim-1 protein kinase activity both in vitro and in intact cells. In this Phase I STTR project, we will address the feasibility of developing new Pim-1 inhibitors with anticancer activity through the following Specific Aims: 1) To optimize the Pim-1 inhibitors using medicinal and computational chemistry; 2) To evaluate the effects of the new compounds on Pim-1 in vitro and in prostate cancer cells; and 3) To evaluate the anticancer efficacy of Pim-1 inhibitors in vivo. These studies provide an efficient process for the synthesis and evaluation of new inhibitors of an emerging target for prostate cancer chemotherapy. Completion of these Specific Aims will provide a clear demonstration of the feasibility of using Pim-1 inhibitors as anticancer agents, and identify the drug candidate for further development in a Phase II STTR project. PUBLIC HEALTH RELEVANCE: The Pim protein kinases are critical enzymes involved in the pathogenesis of prostate cancer. In this project, we have developed methods for synthesizing and testing new inhibitors of Pim kinases. Continued development of these compounds is necessary to provide important new drugs for the treatment of prostate cancer.

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

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