ml-336 is an inhibitor for veev-induced cytopathic effect.alphaviruses like venezuelan equine encephalitis virus (veev) are positive-sense, enveloped, single stranded rna viruses that are widely geographically distributed. veevs are found to be arthropod-borne viruses that are known to cause arthritis, encephalitis, rash, as well as death in humans.
ml336 was identified as a first-in-class probe that inhibited a veev-induced cytopathic effect in three strains of the virus, which were v3526, tc-83, and trinidad donkey, in the low nanomolar range without having cytotoxicity (> 50 μm, selectivity index > 1500). in addition, ml336 could reduce viral titer (more than 7.2 log) dramatically below a 1 μm drug concentration. furthermore, ml336 showed a favorable in vitro pk profile that included moderate blood-brain barrier permeability. more importantly, ml336 seemed to be able to target the veev [1].
32, 20, and 41 nm for tc-83, v3526, and trinidad donkey strains, respectively.
[1] chung d et al. ml336: development of quinazolinone-based inhibitors against venezuelan equine encephalitis virus (veev). probe reports from the nih molecular libraries program. bethesda (md): national center for biotechnology information (us); 2010-2012 dec 17.
