Ro 5-3335 is a new
benzodiazepine highly active in vitro (IC50 = 0.1-1.0 microM [corrected]) against HIV-1 viruses of
AIDS resistant or non-resistant to
zidovudine (AZT). It is also active against HIV-2.
Ro 5-3335 is original by its mechanism of action, acting on the trans-activation factor of transcription (TAT) and non on the
reverse transcriptase. Such as, it could prevent proviral
DNA to express in both evolutive and silent
AIDS resistant or non-resistant to AZT or to other anti-
reverse transcriptase series. In addition, in antagonizing extracellular TAT's actions,
Ro 5-3335 could alleviate the syndrome commonly associated with
AIDS as Kaposi's syndrome. In rodent test,
Ro 5-3335 has no
diazepam-like central effects and presents in comparison to AZT a more favorable therapeutic index. In dog, the elimination half-life, peak concentration and availability are 2 h, 0.8 microM and 85% respectively, after a 1 mg.kg-1 oral dose of
Ro 5-3335. Theoretically,
Ro 5-3335 and now its analogue
Ro 24-7429 seem to possess all virtues to antagonize evolutive and latent
AIDS. Its arrival is timely to cope with the ever increasing resistance phenomena, lengthy development of
AIDS vaccines, exponential contamination of populations worldwide and last but not least possibly to impede evolutions of the disease. Ability to manipulate TAT-mediated activation of HIV-1 genes paves the ways to study conceivable corrections of abnormal gene expressions of
neurotransmitters,
hormones, oncogenes and key
enzymes.