Delavirdine

Abstract

In combination with NRTIs. delavirdine produces sustained improvements in surrogate markers of HIV disease and prolongs the time to virological failure in adult patients with HIV infection. Preliminary data of delavirdine as a component of protease inhibitor-containing triple or quadruple highly active antiretroviral therapy regimens indicate that patients achieve marked improvements in virological and immunological markers. The drug is generally well tolerated, with a transient skin rash, typically of mild to moderate intensity, being the most common adverse effect. Delavirdine is an effective component of recommended antiretroviral treatment strategies for adult patients with HIV infection and, in combination with 2 NRTIs as a first-line therapy, the drug has the advantage of sparing protease inhibitors for subsequent use. Since delavirdine favourably increases plasma concentrations of several protease inhibitors, the drug may also be beneficial as a component of salvage therapy in combination with protease inhibitors.

Predicting new molecular targets for known drugs

“…These two targets share no evolutionary history, functional role, or structural similarity whatsoever. Intriguingly, while Rescriptor's K i for the H 4 receptor is high at 5.3 μM (Table 2, Supplementary Figure 1), this is within its steady-state plasma concentration (C min averages 15 μM) and is consistent with the painful rashes associated with Rescriptor use;45 likewise, H 4 dysregulation has been associated with atopic dermatitis 46. Similarly, the vesicular monoamine transporter (VMAT) inhibitor47 Xenazine binds two different GPCRs at sub-micromolar concentrations (Table 2, Supplementary Figure 1).…”

Structure of HIV-1 nonnucleoside reverse transcriptase inhibitors derivatives of N-benzyl-benzimidazole with different substituents in position 4

“…These compounds can also inhibit human polymerases and cause side effects. Nonnucleoside RT HIV-1 inhibitors (NNRTI), such as nevirapine [10,11], efavirenz [12,13], delavirdine [14,15] interact noncompetitively and are specifically targeted at the viral RT.…”

Structural investigation of HIV-1 nonnucleoside reverse transcriptase inhibitors: 2-Aryl-substituted benzimidazoles

“…HIV-1 reverse transcriptase inhibitors can be divided into: nucleoside analogues, such as azidothymidine (AZT zidovudine) [3,4], 2 0 ,3 0 -dideoxycytidine (DDC, zelcitabine) [5,6], 2 0 ,3 0 -dideoxyinosine (DDI, didanosine) [7,8], 2 0 ,3 0 -didehydro-2 0 ,3 0 -dideoxythymidine (D4T, stavudine) [9,10] and nonnucleoside inhibitors such as nevirapine [11,12], efavirenz [13,14], delavirdine [15,16]. Nucleoside analogues act as competitive inhibitors and can also inhibit human enzymes causing side effects.…”