Natural product inspired novel antimalarials with radical cure potential
Active Project Grant Awarded Last action
- Award ID
- R01AI175444
- Recipient
-
Portland State University UEI H4CAHK2RD945
- Awarding agency
-
National Institute of Allergy and Infectious Diseases
National Institutes of Health, Department of Health and Human Services
- Obligated
- $3,804,366
Award facts
- Assistance listing
- 93.855 Allergy and Infectious Diseases Research
- Completion date 71% complete
- Place of performance
- Portland, OR 97201, USA
Award details come from USAspending.gov.
Description
- Abstract
- Despite the increased attention on the eradication of malaria, prevention and treatment of the disease remain difficult due to i) the emerging resistance to the currently available antimalarials, including front-line artemisinin- based combination therapy (act), II) the absence of a clinically effective vaccine, and III) the spread of insecticide-resistant vectors. Therefore, there is an urgent and continuous need for safe, affordable and novel antimalarial drugs that can combat multiple stages of the parasite life cycle, with novel mechanism(s) of action to overcome the emerging drug resistance. We have developed a natural product inspired novel prodiginine chemotype with broad-spectrum antimalarial activity. Our lead prodiginine candidate meets the aforementioned key requirements, such as 1) novel chemotype; 2) equally effective against a large panel of blood stage plasmodium falciparum MDR parasites; 3) prevents liver stage infection with radical cure ability; 4) effective against sexual blood stage p. Falciparum gametocytes; 5) highly likely operates by a novel mechanism of action; 6) optimal in vitro metabolic stability and in vivo PK profiles with rapid absorption, and long half-life; and 7) synthetically accessible with low-cost production. Our proposed work in this application seeks to develop a novel antimalarial prodiginine drug that is potent against multiple stages of plasmodia, with the potential to circumvent drug resistance, and prevent relapsing malaria infection. The specific goal of this project is to conduct lead optimization studies to produce candidates of novel prodiginines that demonstrate enhanced oral efficacy, safety, solubility, and metabolic/PK profiles that warrant further preclinical development, and to investigate the propensity for drug resistance to selected drug candidates and identify the molecular target(s) through whole genome sequencing and analysis.
Transactions
| Action | Obligated | Date |
|---|---|---|
| Amendment | $622,155 | |
| Amendment | $618,729 | |
| Amendment | $625,296 | |
| Amendment | $625,296 | |
| Amendment | $656,445 | |
| Original award | $656,445 |
Subawards
| Subrecipient | Amount | Awarded |
|---|---|---|
| The Trustees Of Columbia University In The City Of New York | $55,524 | |
| W03K W Reedarmyinstrsch(Wrair) | $524,844 | |
| Dominican University Of California | $111,052 | |
| Portland VA Research Foundation, Inc. | $679,860 |
Quick answers
Who received award R01AI175444?
R01AI175444 was awarded to Portland State University by National Institute of Allergy and Infectious Diseases (National Institutes of Health) on April 4, 2023.
How much is award R01AI175444 worth?
$3,804,366 has been obligated on R01AI175444.
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