Identification of Anti-HIV Lead Compounds Targeting Rev

Award Information
Agency:
Department of Health and Human Services
Branch
n/a
Amount:
$585,387.00
Award Year:
2009
Program:
STTR
Phase:
Phase I
Contract:
1R41AI076087-01A2
Award Id:
93344
Agency Tracking Number:
AI076087
Solicitation Year:
n/a
Solicitation Topic Code:
n/a
Solicitation Number:
n/a
Small Business Information
ADVANCED GENETIC SYSTEMS, INC., 1554 25TH AVE, SAN FRANCISCO, CA, 94122
Hubzone Owned:
N
Minority Owned:
N
Woman Owned:
N
Duns:
154446921
Principal Investigator:
ADAM RENSLO
(415) 514-9698
ADAM.RENSLO@UCSF.EDU
Business Contact:
ROBERT NAKAMURA
() -
Research Institution:
UNIVERSITY OF CALIFORNIA SAN FRANCISCO

UNIVERSITY OF CALIFORNIA SAN FRANCISCO
3333 California St., Ste 315
SAN FRANCISCO, CA, 94143

Nonprofit college or university
Abstract
DESCRIPTION (provided by applicant): There is a significant need for novel HIV therapies given the emergence of viruses resistant to existing drug regimens. The Rev-RRE protein-RNA interaction in HIV plays an essential role in the transport of viral mRNA f rom the nucleus to the cytoplasm where it can be translated or packaged. In preliminary work, two distinct assays targeting the HIV Rev protein identified structurally similar hits possessing a thienopyridine scaffold. Compounds of this class were subseque ntly shown to inhibit HIV replication and to exhibit low toxicity. An expanded study of the thienopyridine class using purchased analogs revealed clear structure-activity relationships (SAR), suggesting a well-defined molecular target and the potential for further improvement in potency through chemical optimization. Here, we propose to conduct a systematic structure-activity study of the thienopyridine family using synthesized analogs and employing a robust panel of antiviral, reporter, and ADME-Tox assays . The initial study of thienopyridines with purchased analogs provided useful information concerning pyridine ring SAR. However, a comprehensive evaluation of these compounds and the identification of the essential pharmacophore imbedded within them will r equire chemical synthesis. Thus, we plan to perform multiple rounds of analog synthesis and screening, allowing emerging SAR to guide further optimization. The successful conclusion of these studies will see the identification of one or more lead chemotype s, thus enabling lead optimization studies in a subsequent phase of work. PUBLIC HEALTH RELEVANCE: A proposed structure-activity study of a promising Rev inhibitor is described. New analogs will be synthesized or procured from vendors and then tested for a ntiviral activity and drug-like properties.

* information listed above is at the time of submission.

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