Radix Pharmaceuticals, Inc.

Potomac, MD, United States

Radix Pharmaceuticals, Inc.

Potomac, MD, United States
SEARCH FILTERS
Time filter
Source Type

Zhu S.,Radix Pharmaceuticals, Inc. | Wang J.,Radix Pharmaceuticals, Inc. | Chandrashekar G.,Radix Pharmaceuticals, Inc. | Smith E.,Radix Pharmaceuticals, Inc. | And 2 more authors.
European Journal of Medicinal Chemistry | Year: 2010

Febrifugine is an alkaloid isolated from Dichroa febrifuga as the active component against Plasmodium falciparum. Adverse side effects have precluded febrifugine as a potential clinical drug. As part of an ongoing malaria chemotherapy project, novel febrifugine analogues were designed and synthesized. Lower toxicity of these newly designed compounds was achieved by reducing or eliminating the tendency to form chemically reactive and toxic intermediates. New compounds possess excellent in vivo antimalarial activity and most of them become less toxic than the natural product febrifugine. Some of the compounds possess a therapeutic index over ten times superior to that of febrifugine and the commonly used antimalarial drug chloroquine. These compounds, as well as the underlying design rationale, may find usefulness in the discovery and development of new antimalarial drugs. © 2010 Elsevier Masson SAS. All rights reserved.


Zhu S.,Radix Pharmaceuticals, Inc. | Chandrashekar G.,Radix Pharmaceuticals, Inc. | Meng L.,Radix Pharmaceuticals, Inc. | Robinson K.,Radix Pharmaceuticals, Inc. | Chatterji D.,Central Drug Research Institute
Bioorganic and Medicinal Chemistry | Year: 2012

Febrifugine is an alkaloid isolated from Dichroa febrifuga Lour as the active component against Plasmodium falciparum, but exhibits toxic side effects. In this study novel febrifugine analogues were designed and efficiently synthesized. New compounds underwent efficacy and toxicity evaluation. Some compounds are much less toxic than the natural product febrifugine and existing antimalarial drugs and are expected to possess wide therapeutic windows. In Aotus monkeys infected with the chloroquine resistant FVO strain of P. falciparum, one interesting compound possesses a 50% curative dose of 2 mg/kg/day and a 100% curative dose of 8 mg/kg/day. These compounds, as well as the underlying design rationale, may find usefulness in the discovery and development of new antimalarial drugs. © 2011 Elsevier Ltd. All rights reserved.


Grant
Agency: Department of Health and Human Services | Branch: | Program: SBIR | Phase: Phase II | Award Amount: 998.18K | Year: 2011

DESCRIPTION (provided by applicant): This project focuses on the development of a novel therapeutic agent for preventing and treating P. falciparum malaria. A two-year Phase I research has discovered novel molecules with potent antimalarial activity against both sensitive and resistant malaria strains in rodent models. Lead compounds are low in toxicity and possess high oral bioavailability and other ideal ADMET properties. The potential for development of resistance was confirmed to be small and a scalablechemical synthesis was also established. After pre-IND meeting with FDA, the proposed SBIR Phase II research was designed. Under Phase II support, we will perform: (I) Scale up synthesis of two lead compounds and cGMP manufacturing of one compound for GLPtoxicity studies; (II) Range-finding toxicity and pharmacokinetics in monkeys; (III) Repeat dose toxicity in monkeys; (IV) Antimalarial activity in Aotus monkeys infected with P. falciparum; (V) GLP toxicology studies: definitive 28-day toxicity study with toxicokinetic, functional observations battery and micronucleus evaluations. An investigational new drug (IND) application will be filed with FDA at the end of Phase II research. The novelty of the project is the discovery of new molecular entities. Theproject involves standard approaches to drug development, but the multidisciplinary team and multi-institution collaboration that has been assembled will accelerate the generation of clinical candidates. PUBLIC HEALTH RELEVANCE: Malaria is one of the most common infectious diseases in the world. It affects approximately 250 million people and leads to 1-3 million death a year. The increasing prevalence of multiple drug resistant strains in most malaria endemic areas has significantly reduced the efficacy of current antimalarial drugs for prophylaxis and treatment of this disease. This project focuses on the development of a novel therapeutic agent for preventing and treating P. falciparum malaria. The novelty of the research is the discovery of new molecular entities. The multidisciplinary team and multi-institution collaboration that has been assembled will accelerate the generation of clinical candidates.


Grant
Agency: Department of Health and Human Services | Branch: | Program: SBIR | Phase: Phase II | Award Amount: 1.24M | Year: 2012

DESCRIPTION (provided by applicant): The proposed research focuses on the development of novel therapeutic agents for the prevention and treatment of malaria caused by P. falciparum. A previous Phase I project has discovered novel molecules with potent antimalarial activity against both sensitive and multidrug resistant malaria strains in some in vitro and in vivo models. Lead compounds are low in toxicity and possess high oral bioavailability. The potential for development of resistance was confirmed to besmall and a scalable chemical synthesis was also established. The current SBIR Phase II research was designed after pre-IND meeting with FDA. Under Phase II support, the two lead compounds will be synthesized on a large scale. Range-finding toxicity, repeat dose toxicity, and pharmacokinetic studies will be conducted in monkey models. Antimalarial efficacy will be evaluated in Aotus monkeys infected with P. falciparum. One compound with desired toxicity, efficacy, and pharmacokinetic properties will be selected for cGMP manufacturing. This compound will then undergo GLP toxicology studies: definitive 28-day toxicity study with toxicokinetic, functional observations battery and micronucleus evaluations. An investigational new drug (IND) application will be filed with FDA at the end of Phase II research. The novelty of the project is the discovery of new molecular entities. The project involves standard approaches to drug development, but the multidisciplinary team and multi- institution collaboration that hasbeen assembled will accelerate the generation of clinical candidates. PUBLIC HEALTH RELEVANCE: Malaria is one of the most common infectious diseases in the world. It affects approximately 225 million people and leads to about 791,000 death a year. The increasing prevalence of multiple drug resistant strains in most malaria endemic areas has significantly reduced the efficacy of current antimalarial drugs for prophylaxis and treatment of this disease. This project focuses on the development of a novel therapeutic agent for preventing and treating P. falciparum malaria. The novelty of the research is the discovery of new molecular entities. The multidisciplinary team and multi-institution collaboration that has been assembled will accelerate the generation of clinical candidates.


PubMed | Radix Pharmaceuticals, Inc.
Type: Journal Article | Journal: Bioorganic & medicinal chemistry | Year: 2012

Febrifugine is an alkaloid isolated from Dichroa febrifuga Lour as the active component against Plasmodium falciparum, but exhibits toxic side effects. In this study novel febrifugine analogues were designed and efficiently synthesized. New compounds underwent efficacy and toxicity evaluation. Some compounds are much less toxic than the natural product febrifugine and existing antimalarial drugs and are expected to possess wide therapeutic windows. In Aotus monkeys infected with the chloroquine resistant FVO strain of P. falciparum, one interesting compound possesses a 50% curative dose of 2mg/kg/day and a 100% curative dose of 8 mg/kg/day. These compounds, as well as the underlying design rationale, may find usefulness in the discovery and development of new antimalarial drugs.

Loading Radix Pharmaceuticals, Inc. collaborators
Loading Radix Pharmaceuticals, Inc. collaborators