Novel Inhibitors of Pim Protein Kinases

Award Information
Agency:
Department of Health and Human Services
Branch
n/a
Amount:
$257,864.00
Award Year:
2009
Program:
STTR
Phase:
Phase I
Contract:
1R41CA135804-01A2
Award Id:
93505
Agency Tracking Number:
CA135804
Solicitation Year:
n/a
Solicitation Topic Code:
n/a
Solicitation Number:
n/a
Small Business Information
VORTEX BIOTECHNOLOGY CORPORATION, 26 HOPETOWN RD, MOUNT PLEASANT, SC, 29464
Hubzone Owned:
N
Minority Owned:
N
Woman Owned:
N
Duns:
827435749
Principal Investigator:
ANDREWKRAFT
(843) 792-8284
KRAFT@MUSC.EDU
Business Contact:
CHARLESSMITH
() -
Research Institute:
MEDICAL UNIVERSITY OF SOUTH CAROLINA

Office of Research and Sponsored Programs
19 Hagood Ave., Suite 606
CHARLESTON, SC, 29425 4919

Nonprofit college or university
Abstract
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 intraepitheli al 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 Rbnul l 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 ce lls. 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 evalu ate 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 developme nt 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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