Efavirenz (DMP 266) is a Human Immunodeficiency Virus 1 Non-Nucleoside Analog Reverse Transcriptase Inhibitor, acting as a Non-Nucleoside Reverse Transcriptase Inhibitor, Cytochrome P450 3A Inducer, Cytochrome P450 2B6 Inducer, Cytochrome P450 2C9 Inhibitor, Cytochrome P450 2C19 Inhibitor, and Cytochrome P450 3A4 Inhibitor, classified as a Non-Nucleoside Analog.

HIV-1:2.93 nM (Ki)

Efavirenz has direct inhibitory effect on the mitochondrial respiratory function of cultured glioblastoma and differentiated neuroblastoma cell lines[2]. ER stress markers, including CHOP and GRP78 expression (both protein and mRNA), phosphorylation of eIF2a, and presence of the spliced form of XBP1 are upregulated. Efavirenz also enhances cytosolic Ca2+ content and induced morphological changes in the ER suggestive of ER stress. This response is greatly attenuated in cells with altered mitochondrial function (Rho). The effects of Efavirenz on the ER, and particularly in regard to the mitochondrial involvement, differs from those elicited by a standard pharmacological ER stressor[3].

Efavirenz leads to arterial stiffening but, for the dose and duration tested, did not lead to elevated plaque progression in ApoE(-/-) mice[4].

Recombinant RT enzymes are expressed, purified, and assessed for inhibition by Efavirenz (L-743726). Ki and Kii values are determined for each enzyme tested. The wild-type RT exhibited exclusively noncompetitive inhibition kinetics (data not shown), and, therefore, the Ki and Kii values are identical. Pure noncompetitive inhibition is not assumed for the mutant enzymes, and, hence, the values of both Ki and Kii are obtained from the linear mixed-type inhibition equation. The two- to threefold differences between the Ki and Kii values probably reflect a small contribution of competitive inhibition with the mutant RTs[1].

The OCR(O2 consumption rate) is measured in SH-SY5Y and U-251 mg cells exposed to vehicle, 10 μM efavirenz or 25 μM efavirenz for 1 h. (Only for Reference)