Novel prodrugs for treatment of human CMV infection

Award Information
Agency: Department of Health and Human Services
Branch: N/A
Contract: 1R43AI091216-01
Agency Tracking Number: AI091216
Amount: $591,457.00
Phase: Phase I
Program: SBIR
Awards Year: 2010
Solicitation Year: 2010
Solicitation Topic Code: NIAID
Solicitation Number: PHS2010-2
Small Business Information
DUNS: 156551699
HUBZone Owned: N
Woman Owned: N
Socially and Economically Disadvantaged: N
Principal Investigator
 (734) 663-4233
Business Contact
Phone: (734) 663-4233
Research Institution
DESCRIPTION (provided by applicant): As a result of the widespread use of antiviral prophylaxis and pre-emptive therapy, the incidence and severity of human cytomegalovirus (HCMV) disease and its indirect effects have been significantly reduced. However, there is an increasing recognition of antiviral drug resistance. In particular, with the advent of oral ganciclovir (GCV) prophylaxis against HCMV, concerns about emergence of GCV resistance (GCV-R) have been raised. GCV-R can be successfully treated with nucleotide phosphonate drugs such as Cidofovir (CDV) and 9-(S)-(3- hydroxy-2-phosphonomethoxy-propyl)adenine (HPMPA). However, these drugs are significantly limited as oral therapeutics because, as a group, they are poorly absorbed when administered orally. We have developed a prodrug strategy designed to improve the oral absorption of the nucleotide phosphonate drugs, CDV and HPMPA, such that they will be effective anti-HCMV oral therapeutic agents. In the phase 1 portion of the project, we propose to synthesize a novel series of CDV and HPMPA prodrugs and evaluate their stability, metabolism and antiviral activity against sensitive and GCV-R resistant strains of CMV. Those prodrugs showing good stability and simplified metabolism will be tested for oral bioavailability. This work will lay the scientific foundation for development of an effective, oral agent against ganciclovir resistant HCMV. For this project, we have established collaborations with Prof. Charles McKenna (prodrug design and synthesis) at the University of Southern California and Prof. John Drach (virological studies) at the University of Michigan. PUBLIC HEALTH RELEVANCE: There is an increasing need for new drugs that are effective against drug-resistant strains of the human cytomegalovirus that are becoming more numerous as long term treatments against the virus are developed. A series of new drugs is available but they are not suitable for commercialization because they are not well absorbed when given orally. Thus, the goal of this work is to modify these new drugs such that they are well absorbed when taken orally and will be effective against the human cytomegalovirus.

* Information listed above is at the time of submission. *

Agency Micro-sites

SBA logo
Department of Agriculture logo
Department of Commerce logo
Department of Defense logo
Department of Education logo
Department of Energy logo
Department of Health and Human Services logo
Department of Homeland Security logo
Department of Transportation logo
Environmental Protection Agency logo
National Aeronautics and Space Administration logo
National Science Foundation logo
US Flag An Official Website of the United States Government