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Preclinical Development of JS-K, a Novel NO-Generating Prodrug for Cancer

Award Information

Department of Health and Human Services
Award ID:
Program Year/Program:
2010 / SBIR
Agency Tracking Number:
Solicitation Year:
Solicitation Topic Code:
Solicitation Number:
Small Business Information
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Woman-Owned: No
Minority-Owned: No
HUBZone-Owned: No
Phase 1
Fiscal Year: 2010
Title: Preclinical Development of JS-K, a Novel NO-Generating Prodrug for Cancer
Agency: HHS
Contract: 1R44CA156812-01
Award Amount: $119,742.00


DESCRIPTION (provided by applicant): Despite notable achievements over the past two decades, cancer remains a challenging 21st century epidemic demanding new, more effective drugs. Nitric oxide (NO) is well known to kill cancer cells without harming norma l bone marrow cells, but until now has not been used directly to treat cancer because of its effect to lower blood pressure. JSK Therapeutics (JSKT) has designed a class of diazeniumdiolate prodrugs that release NO upon interaction with glutathione in a re action catalyzed by glutathione-S-transferase, which is expressed at significantly higher concentrations in cancer compared to normal cells. JSKT has screened a library of these compounds and has identified one, JS-K, as the most active compound of this fa mily. In the Rapid Access to Intervention Development (RAID) program at the NCI, JS-K is active against the entire NCI 60-cell screen. JS-K has potent and broad anticancer activity against solid tumors and hematologic malignancies in multiple laboratorie s but shows no toxicity against normal bone marrow, making it critically important to the future of cancer therapy. In mouse xenograft models of human tumors, JS-K is highly effective against acute myeloid leukemia, prostate cancer, hepatocellular carcinom a, multiple myeloma and non-small cell lung cancer. Significant work has begun on this promising therapy and has shown that JS-K is difficult to solubilize and has a short half-life in vivo. Previous NIH funding has allowed a solution for these challenges: a stable nanoscale P123 Pluronic(R) micelle intravenous (IV) formulation for JS-K has been developed, and scale- up production and formulation of 1 kg of JS-K in P123 Pluronic(R) micelles is currently under production in compliance with Good Manufacturing Practices. JSKT submits this Fast Track Phase I/II SBIR application to perform the standard acute and subchronic pre-clinical animal toxicology studies needed using Good Laboratory Practices (GLP) to support a successful Investigational New Drug (IND) app lication to the FDA. JSKT hypothesizes that P123 Pluronic(R) micelle JS-K will prove non-toxic in therapeutic doses needed to treat cancer in humans. In Phase I, JSKT will accomplish 3 deliverables: 1) perform acute IV toxicology of JS-K in rats; 2) perfor m bacterial mutagenicity (Ames) testing; and 3) draft the chemistry and manufacturing section for a JS-K IND application. In Phase II, JSKT will accomplish 2 additional deliverables: 1) develop and validate using GLP procedures a sensitive LS/MS/MS assay f or measuring JS-K in biologic fluids; and 2) complete acute IV toxicology studies of JS-K in dogs and 28-day subchronic IV toxicology studies of JS-K in rats and dogs. Upon completion of this project, JSKT will have all the essential pharmacology, toxicolo gy and manufacturing information to submit a successful IND to begin Phase I safety trials of micelle JS-K in humans at the Huntsman Cancer Institute in Salt Lake City, UT. Commercialization of this novel cancer fighting drug, JS-K, will establish a new pa radigm in cancer therapy, improve the quality of life for cancer patients and their families with less painful, more effective treatments, and provide a sustainable benefit worldwide. PUBLIC HEALTH RELEVANCE: This project will continue the develop ment of a highly effective new drug called JS-K, which will treat and kill multiple cancers. JS-K will kill these cancers by a new, more selective and measurably less toxic mechanism, making it entirely relevant to today's world. This new drug then goes on e step further: it will improve the quality of life for cancer patients, their caregivers and families by providing a significantly more effective and less painful therapy than is currently available.

Principal Investigator:

Gregory J. Johnson

Business Contact:

Small Business Information at Submission:


EIN/Tax ID: 126317571
Number of Employees: N/A
Woman-Owned: No
Minority-Owned: No
HUBZone-Owned: No