Latest research on TMC278

Rilpivirine is non-nucleoside reverse transcriptase inhibitor (NNRTI) which is used for the treatment of HIV-1 infections in treatment-naive patients. It is a diarylpyrimidine, a class of molecules that resemble pyrimidine nucleotides found in DNA. Because of its flexible chemical structure, resistance of rilpivirine is less likely to develop than other NNRTI's. FDA approved on May 20, 2011.

Latest findings

On the other side, the TIBO synthesis path successively led to DAPY–diaril-pyrimidine etravirine (TMC278) and rilpivirine (TMC120), and dapivirine (TMC125) of Figure 2 and Figure 3, which have so far been approved for clinical use [10,12,13,23,67]. [source, 2015]
, and TMC278 LA, a long-acting injectable formulation of the novel NNRTI TMC278 (ripilvirine) [source, 2015]
We have chosen in our study the high-resolution structure (1.8 Å) of the complex of HIV-1RT with (4-{[4-({4-[(E)-2-cyanoethenyl]-2,6-dimethylphenyl}amino)pyrimidin-2-yl]amino}benzonitrile (also called TMC278 or rilpivirine), a highly effective drug in treating wild-type and drug-resistant HIV-1 infections in clinical trials [111]. [source, 2015]
Rilpivirine (RPV, TMC278), a non-nucleoside reverse transcriptase inhibitor (NNRTI), is a diarylpyrimidine derivative that inhibits HIV reverse transcriptase by binding to a hydrophobic pocket near the active site of the enzyme, and consequently preventing transcription of viral RNA. [source, 2015]
This structure of the HIV-1 RT heterodimer, in complex with the TMC278 drug, has the PDB code entry 2ZD1 and reflects an open-cleft conformation resembling those seen in other complexes of RT with nonnucleoside reverse transcriptase inhibitors (NNRTIs) [32,42,112]. [source, 2015]
In our study we have considered, for the receptor structure, only the region containing the binding site of the TMC278 drug. [source, 2015]
Both TMC278 LA and GSK744 LA have a pharmacokinetic profile that allows monthly to trimonthly parenteral dosing using a nanosuspension formulation. [source, 2014]
The 744LA formulation in combination with the long-acting rilpivirine formulation (TMC278 LA) is being developed for use in treatment of HIV-infected patients. [source, 2014]
In humans, RPV efficacy was established in the THRIVE (TMC278 against HIV, in a once daily RegImen vs Efavirenz) and ECHO (Early Capture HIV Cohort Study) studies [36,37]. [source, 2014]
In a recent study, comparing the performance of the newly released Edurant II® endograft in patients with friendly and hostile infrarenal aortic anatomy eligible for EVAR, the necessity of troubleshooting techniques was significantly higher in the hostile group. [source, 2014]