Research for antimalarial drugs: Mainly JPMW project
2001
Otoguro, K. (Kitasato Inst., Tokyo (Japan))
JPMW project was established through a public/private sector partnership among the Japanese Pharmaceutical Companies, Ministry of Health and Welfare, Japan, and WHO/TDR on 26 October 1999, in order to discover the new antimalarial drug from Japan. Behind the establishment of this project was the Roll Back Malaria Initiative that was proposed by WHO in 1998 and the HASHIMOTO Initiative that was proposed by Government of Japan in the same year. Both initiatives recognized that emerging and re-emerging infectious diseases could not be controlled with existing tools. The Kitasato Institute is playing an important role as the screening center (JSC) in JPMW project. JSC is carrying out the evaluation for antimalarial activity of the compounds from the companies, along with some of its own natural products, both in vitro and in vivo, using the drugs resistant strain of Plasmodium falciparum and the rodent malaria model, respectively. JSC has assayed 7,648 samples as in vitro screening until 31 March 2001. JSC selected 98 samples that had an activity score 3 (the most active). Furthermore, JSC has assayed 32 compounds as in vivo screening until 31 March 2001. JSC selected 3 compounds that had an activity score 3 in vivo. Now, those 3 compounds are testing by further evaluation using the rodent malaria models. To the present, none of these proved active enough to be considered as a lead compound, but we found that K99-4013 (X-206) possesses a narrow therapeutic window in the rodent malaria model compared with its selective and strong inhibitory effect on malaria in vitro. JSC will continue the evaluation of antimalarial drugs using the in vitro and in vivo screening systems.
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