Designed Antimalarial Agents Overcoming Chloroquine-Resistance

Award Information
Agency:
Department of Health and Human Services
Branch
n/a
Amount:
$1,327,608.00
Award Year:
2009
Program:
STTR
Phase:
Phase II
Contract:
2R42AI072923-02A1
Award Id:
85300
Agency Tracking Number:
AI072923
Solicitation Year:
n/a
Solicitation Topic Code:
n/a
Solicitation Number:
n/a
Small Business Information
DESIGNMEDIX, INC., 2828 Corbett Ave Suite 140A, PORTLAND, OR, 97201
Hubzone Owned:
N
Minority Owned:
N
Woman Owned:
N
Duns:
623389009
Principal Investigator:
DAVID PEYTON
(503) 725-3875
PEYTOND@PDX.EDU
Business Contact:
HAROLD PEYTON
() -
sandysh@pacifier.com
Research Institute:
PORTLAND STATE UNIVERSITY

PORTLAND STATE UNIVERSITY
BOX 751
PORTLAND, OR, 97207 7600

Nonprofit college or university
Abstract
DESCRIPTION (provided by applicant): DesignMedix has developed a novel class of compounds to address the pressing need for an orally available, inexpensive drug to counter the spread of chloroquine-resistant malaria. Preliminary data showed that this novel class of molecules, called reversed chloroquines (RCQs), acts against both chloroquine- resistant and chloroquine-sensitive malaria in vitro. In our Phase I study, we demonstrated the feasibility of this approach both in vitro and in an in vivo animal m odel, showing that compounds were orally available, had in vivo effectiveness similar to that of chloroquine, and were very effective against chloroquine-resistant human malaria parasites in vitro. The goal of this Phase II project is to choose and move sp ecific RCQ drug candidates into preclinical studies to advance commercialization of a therapeutic product. In addition to focusing on the clearly-identified lead compounds from the Phase I, we will enlarge the initial panel of RCQ structures based on resul ts from that initial feasibility study, and test them against chloroquine-sensitive and chloroquine-resistant malaria in human red blood cells in vitro, as well as for other in vitro tests for solubility, central nervous system receptor activity, mutagenic activity, and cytotoxicity. Oral availability will begin with mice, as will in vivo toxicity evaluations. The most promising of the original and modified RCQ candidates will be moved forward toward preclinical study through evaluation in animal models for their pharmacokinetics and metabolism. We expect that at the conclusion of the Phase II project, one or more lead RCQ drug candidates will be ready for study in a primate model system of chloroquine-resistant malaria, the final step before full preclinica l GLP toxicity and ADME studies for filing an IND application for human clinical studies. DesignMedix is directing this study specifically against P. falciparum, the most problematic human malaria variant, but RCQs also should be effective against the othe r human malarias. The product addresses market opportunities that include large endemic markets with international non-profit and government buyers, smaller but substantial markets for military and travelers, as well as private markets in developing countr ies such as India and China. Further development of the product will be carried out with resources from multiple sources, including equity investment, company and global health non-profit partnerships, and additional grant funding. PUBLIC HEALTH RELEVANCE: Malaria is a disease that infects almost half a billion people annually and kills between one and three million people, most of whom are either children or pregnant women. Malaria is increasing, partly because the parasite that causes malaria has evolved into strains that are resistant to our best drugs for treating the disease. This work is to develop further promising lead candidates from a new class of drugs, reversed chloroquines' (RCQs), designed to overcome this resistance.

* information listed above is at the time of submission.

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