OLIGONUCLEOTIDES AS PRODRUGS FOR ANTICANCER DRUGS

Award Information
Agency: Department of Health and Human Services
Branch: N/A
Contract: 1R43CA091678-01A1
Agency Tracking Number: CA091678
Amount: $100,000.00
Phase: Phase I
Program: SBIR
Awards Year: 2002
Solicitation Year: N/A
Solicitation Topic Code: N/A
Solicitation Number: N/A
Small Business Information
RELIABLE BIOPHARMACEUTICAL CORPORATION
RELIABLE BIOPHARMACEUTICAL CORP., BOX 2517, 1945 WALTON RD, ST. LOUIS, MO, 63114
DUNS: N/A
HUBZone Owned: N
Woman Owned: N
Socially and Economically Disadvantaged: N
Principal Investigator
 UMASHANKER SAMPATH
 (314) 429-7700
 USAMPATH@RELIABLEBIOPHARM.COM
Business Contact
 JOSEPH TOCE
Phone: (314) 429-7700
Email: JTOCE@RELIABLEBIOPHARM.COM
Research Institution
N/A
Abstract
DESCRIPTION (provided by applicant): The overall objected is to develop an easy controlled method of delivery for anticancer nucleoside drugs [cytarabine (araC); cladribine] in their polymeric form as oligonucleotides. The monomer drugs, currently are delivered slowly through continuous infusion in a hospital to avoid doses-related toxicities. They are phosphorytlated in the cytoplasm to the monophosphate the active metabolite. We have shown that poly araC, an oligonucleotide prodrug is degraded by nucleases to cytarabine monophosphate [araCMP] and that chimeric oligonucleotides [the prodrug] containing cytarabine and 2'O-alkyl nucleoside "speed bumps" degrade slower. Also, poly-araC, when transfected into HL-60 cells was degraded to araCMP and caused cell death. The specific aim in Phase I is to prepare various chimeric prodrug oligonucleotides with araC and 2'OMe-araU and study the rates of degradation in vitro and in HL6O and araC-resistant HL-60 cells. We expect to show that the araC-resistant cells are susceptible to araCMP, the metabolite from our prodrug oligonucleotides. We intend to show that the degradation is dependent upon 2'OMe-araU, the "speed bump nucleoside" used and that will be indicative of a controlled release version of these drugs. In Phase ll, the pharmacology, toxicology and efficacy of these oligonucleotide prodrugs in animals will be studied. PROPOSED COMMERCIAL APPLICATION: The proposed anticancer nucleoside prodrugs will localize inside the cytoplasm and in a controlled or timed release manner, degrade directly to the active metabolite {nucleoside monophosphate} in therapeutically relevant concentrations and thus reduce the cost of therapy by reducing the dose and the toxicity-related risks.

* information listed above is at the time of submission.

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