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POLYHYDROXYPHENYL-CONJUGATES FOR ANTITUMOR ACTIVITY

Award Information

Agency:
Department of Health and Human Services
Branch:
N/A
Award ID:
11157
Program Year/Program:
1989 / SBIR
Agency Tracking Number:
11157
Solicitation Year:
N/A
Solicitation Topic Code:
N/A
Solicitation Number:
N/A
Small Business Information
MOLECULES FOR HEALTH, INC.
800 E. LEIGH STREET SUITE 206-7 RICHMOND, VA 23219 1534
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Woman-Owned: No
Minority-Owned: No
HUBZone-Owned: No
 
Phase 1
Fiscal Year: 1989
Title: POLYHYDROXYPHENYL-CONJUGATES FOR ANTITUMOR ACTIVITY
Agency: HHS
Contract: N/A
Award Amount: $49,962.00
 

Abstract:

THE REDUCTIVE CONVERSION OF RIBONUCLEOTIDES TO DEOXYRIBONUCLEOTIDES, CATALYZED BY RIBONUCLEOTIDE REDUCTASE,IS A CRUCIAL AND RATE-LIMITING REACTION IN THE DNA BIOSYNTHETIC PATHWAY, AND REPRESENTS A LOGICAL TARGET FOR CANCER CHEMOTHERAPY. IN RESPONSE TO THIS NEED, A SERIES OF RIBONUCLEOTIDE REDUCTASE INHIBITORS, BASED ON A VICINAL POLYHYDROXYPHENYL STRUCTURE, HAVE BEEN DEVELOPED. THE COMPOUND OF THE INITIAL SERIES WITH THE BEST ANTITUMOR ACTIVITY IN ANIMAL TUMOR MODELS, DIDOX, HAS ENTERED HUMAN CLINICAL TRIALS. THE PURPOSE OF THIS PROJECT IS TO ENHANCE THE THERAPEUTIC EFFICACY OF THE ANTICANCER DRUGS, DIDOX AND AMIDOX, BY CONJUGATING THEM TO A BIOCOMPATIBLE POLYMER. IT IS HOPED THAT THE DRUG-POLYMER CONJUGATE WILL REDUCE THE RATE OF DIDOX METABOLISM AND ELIMINATION TO ACHIEVE A LONGERBIOLOGICAL HALF-LIFE. INITIAL HUMAN CLINICAL PHARMACOKINETIC STUDIES INDICATE THAT DIDOX HAS A SHORT HALF-LIFE IN THE PLASMA. DURING PHASE I, DIDOX AND AMIDOX AND THE BIOCOMPATIBLE POLYMER WILL BE PREPARED AND THE DRUG WILL BE ATTACHED DIRECTLY TO THE POLYMER OR THROUGH A DEGRADABLE SPACER GROUP. THE DRUG-POLYMER ADDUCTS WILL BE CHARACTERIZED, AND STUDIES WILL BE PERFORMED TO DETERMINE WHETHER THEY INHIBIT MAMMALIAN RIBONUCLEOTIDE REDUCTASE BEFORE AND AFTER TREATMENT WITH MICROSOMAL AND LYSOSOMAL ENZYMES. CYTOTOXICITY AGAINST TISSUE CULTURE CELLS WILL BE ASCERTAINED. MOST IMPORTANTLY, THE ANTITUMOR ACTIVITY OF THE DRUG-POLYMER CONJUGATES IN THE L1210 LEUKEMIA AND LEWIS LUNG TUMOR MODELS WILL BE DETERMINED.

Principal Investigator:


0

Business Contact:

Small Business Information at Submission:

Molecules For Health Inc
3313 Gloucester Rd Richmond, VA 23227

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