Mechanism of action
Etravirine is a second-generation non-nucleoside reverse transcriptase inhibitor (NNRTI), designed to be active against HIV with mutations that confer resistance to the two most commonly prescribed first-generation NNRTIs, mutation K103N for efavirenz and Y181C for nevirapine. This potency appears to be related to etravirines flexibility as a molecule. Etravirine is a diarylpyrimidine (DAPY), a type of organic molecule with some conformational isomerism that can bind the enzyme reverse transcriptase in multiple conformations, allowing for a more robust interaction between etravirine and the enzyme, even in the presence of mutations. Other diarylpyrimidine-analogues are currently being used as anti-HIV agents, notably rilpivirine. Warnings and risks
In 2009, the prescribing information for etravirine was modified to include "postmarketing reports of cases of Stevens–Johnson syndrome, toxic epidermal necrolysis and erythema multiforme, as well as hypersensitivity reactions characterized by rash, constitutional findings, and sometimes organ dysfunction, including liver failure. Intelence therapy should be immediately discontinued when signs and symptoms of severe skin or hypersensitivity reactions develop." Repositioning
Etravine has been studied for use in a drug repositioning application. In a paper published in the medical journal Movement Disorders, etravirine was shown to cause an increase in frataxin production. Frataxin deficiency is a key component to Friedreichs ataxia, a genetically inherited disease that causes the progressive loss of coordination and muscle strength leading to motor incapacitation and the full-time use of a wheelchair. Chemistry
Etravine forms as colourless orthorhombic crystals in space group Pna21. The structures of these and of a number of solvate and salt forms have been reported. References
External links
"Etravirine".
Drug Information Portal. U.S. National Library of Medicine.