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IC50: 32, 20, and 41 nM for TC-83, V3526, and Trinidad donkey strains, respectively.

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.

In vitro: 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].

In vivo: Currently, there is no animal in vivo data reported.

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