Avermectin

Eight different avermectins were isolated in four pairs of homologue compounds (A1, A2, B1, B2), with a major (a-component) and minor (b-component) component usually in ratios of 80:20 to 90:10.

Half of the 2015 Nobel Prize in Physiology or Medicine was awarded to William C. Campbell and Satoshi Ōmura for discovering avermectin,[4] "the derivatives of which have radically lowered the incidence of river blindness and lymphatic filariasis, as well as showing efficacy against an expanding number of other parasitic diseases."

In 1978, an actinomycete was isolated at the Kitasato Institute from a soil sample collected at Kawana, Ito City, Shizuoka Prefecture, Japan.

Early tests indicated that some of the whole, fermented broths were active against Nematospiroides dubius in mice over at least an eight-fold range without notable toxicity.

The compounds were finally characterized and the novel species that produced them were described by a team at Merck in 1978, and named Streptomyces avermitilis (with the adjective probably intended to mean that it kills worms).

They show activity against a broad range of nematodes and arthropod parasites of domestic animals at dose rates of 300 μg/kg or less (200 μg/kg ivermectin appearing to be the common interspecies standard, from humans to horses to house pets, unless otherwise indicated).

[citation needed] Unlike the macrolide or polyene antibiotics, they lack significant antibacterial or antifungal activities.

[17] Avermectin has been reported to block LPS-induced secretion of tumor necrosis factor, nitric oxide, prostaglandin E2, and increase of intracellular concentration of Ca2+.

[1] The initial aglycon is subsequently released from the thioesterase domain of AVES 4 by formation of an intramolecular cyclic ester.