نتایج جستجو برای: cycloguanil pamoate

تعداد نتایج: 304  

Journal: :Proceedings of the National Academy of Sciences of the United States of America 2012
Yongyuth Yuthavong Bongkoch Tarnchompoo Tirayut Vilaivan Penchit Chitnumsub Sumalee Kamchonwongpaisan Susan A Charman Danielle N McLennan Karen L White Livia Vivas Emily Bongard Chawanee Thongphanchang Supannee Taweechai Jarunee Vanichtanankul Roonglawan Rattanajak Uthai Arwon Pascal Fantauzzi Jirundon Yuvaniyama William N Charman David Matthews

Malarial dihydrofolate reductase (DHFR) is the target of antifolate antimalarial drugs such as pyrimethamine and cycloguanil, the clinical efficacy of which have been compromised by resistance arising through mutations at various sites on the enzyme. Here, we describe the use of cocrystal structures with inhibitors and substrates, along with efficacy and pharmacokinetic profiling for the design...

2016
C. Brandon Ogbunugafor C. Scott Wylie Ibrahim Diakite Daniel M. Weinreich Daniel L. Hartl

The adaptive landscape analogy has found practical use in recent years, as many have explored how their understanding can inform therapeutic strategies that subvert the evolution of drug resistance. A major barrier to applications of these concepts is a lack of detail concerning how the environment affects adaptive landscape topography, and consequently, the outcome of drug treatment. Here we c...

2011
Marna S. Costanzo Kyle M. Brown Daniel L. Hartl

BACKGROUND Patterns of emerging drug resistance reflect the underlying adaptive landscapes for specific drugs. In Plasmodium falciparum, the parasite that causes the most serious form of malaria, antifolate drugs inhibit the function of essential enzymes in the folate pathway. However, a handful of mutations in the gene coding for one such enzyme, dihydrofolate reductase, confer drug resistance...

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