OLIGONUCLEOTIDES AS PRODRUGS FOR ANTICANCER DRUGS

Award Information
Agency:
Department of Health and Human Services
Branch
n/a
Amount:
$100,000.00
Award Year:
2002
Program:
SBIR
Phase:
Phase I
Contract:
1R43CA091678-01A1
Award Id:
60008
Agency Tracking Number:
CA091678
Solicitation Year:
n/a
Solicitation Topic Code:
n/a
Solicitation Number:
n/a
Small Business Information
RELIABLE BIOPHARMACEUTICAL CORP., BOX 2517, 1945 WALTON RD, ST. LOUIS, MO, 63114
Hubzone Owned:
N
Minority Owned:
N
Woman Owned:
N
Duns:
n/a
Principal Investigator:
UMASHANKERSAMPATH
(314) 429-7700
USAMPATH@RELIABLEBIOPHARM.COM
Business Contact:
JOSEPHTOCE
(314) 429-7700
JTOCE@RELIABLEBIOPHARM.COM
Research Institute:
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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