Ivermectin: A Reflection on Simplicity (Nobel Lecture)

Campbell, William C.

doi:10.1002/anie.201601492

Cited by 30 publications

(44 citation statements)

References 16 publications

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“…Parasite nematodes cause morbidity in animals and humans and macrocyclic lactones (ML), such as ivermectin (IVM), are important anthelmintic drugs for therapy ( Campbell, 2016 , Ōmura, 2016 ). However, the long-term use of ML has led to the development of drug resistance, challenging therapeutic control ( Kaplan and Vidyashankar, 2012 ).…”

Section: Introductionmentioning

confidence: 99%

Structural model, functional modulation by ivermectin and tissue localization of Haemonchus contortus P-glycoprotein-13

David

Lebrun

Duguet

et al. 2018

International Journal for Parasitology: Drugs and Drug Resistan

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Haemonchus contortus, one of the most economically important parasites of small ruminants, has become resistant to the anthelmintic ivermectin. Deciphering the role of P-glycoproteins in ivermectin resistance is desirable for understanding and overcoming this resistance. In the model nematode, Caenorhabditis elegans, P-glycoprotein-13 is expressed in the amphids, important neuronal structures for ivermectin activity. We have focused on its ortholog in the parasite, Hco-Pgp-13. A 3D model of Hco-Pgp-13, presenting an open inward-facing conformation, has been constructed by homology with the Cel-Pgp-1 crystal structure. In silico docking calculations predicted high affinity binding of ivermectin and actinomycin D to the inner chamber of the protein. Following in vitro expression, we showed that ivermectin and actinomycin D modulated Hco-Pgp-13 ATPase activity with high affinity. Finally, we found in vivo Hco-Pgp-13 localization in epithelial, pharyngeal and neuronal tissues. Taken together, these data suggest a role for Hco-Pgp-13 in ivermectin transport, which could contribute to anthelmintic resistance.

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Section: Introductionmentioning

confidence: 99%

Structural model, functional modulation by ivermectin and tissue localization of Haemonchus contortus P-glycoprotein-13

David

Lebrun

Duguet

et al. 2018

International Journal for Parasitology: Drugs and Drug Resistan

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“…Three researchers, Bill Campbell and Professor Satoshi Ōmura for the discovery of avermectin and Youyou Tu for the discovery of the artemisinin awarded the prize. These discoveries revolutionized the therapeutic options for parasitic diseases such as Onchocerciasis (River blindness), Lymphatic filariasis, Malaria, etc., whcih significantly reduced the percentages of the morbidity and mortality [45][46][47]. These findings raised the interest in natural products and their therapeutic applications not only for parasitic diseases but also to lethal threats such as cancer and AIDS.…”

Section: Discovery Of Avermectin and Artemisinin-2015 Nobel Prizementioning

confidence: 93%

Physiology and Medicine: The Gifted Saga of the Last Decade

Rao¹,

Nb²

2016

Anat Physiol

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Over the last century, Science and Technology moved forward and witnessed exceptional inventions and discoveries due to individual and collaborative research efforts. This momentum opened doors for the deep understanding of biological systems by which it permitted the advancement in technologies and designing of new tools in biomedical field. Since 1901, discoveries and inventions in various fields of science (Chemistry, Physics, Physiology and Medicine, Economics) including literature which can influence the betterment of human race were being awarded with Nobel Prize. Over the past decade, numerous groundbreaking discoveries in physiology and medicine have been reported. This short note is intended to summarize the significance of these findings and few remarkable controversies associated with them.

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“…This receptor is also a member of the Cys-loop family and is very different from mammalian ionotropic glutamate receptors. GluCl is sensitive to ivermectin, which is used clinically as an antiparasitic agent (Campbell, 2016). The receptor is heteropentameric comprising two subunits (GluClα and GluClβ), both of which need to be expressed to have a functioning channel (Slimko et al, 2002).…”

Section: Self-regulating Chemogeneticsmentioning

confidence: 99%