However, a role for this interaction has not been confirmed in the context of intact mature virions or in the target cell. Together, these observations indicate that IN protein does not directly affect the virion-associated enzymatic activity of RT, but do not exclude the direct interaction between IN and RT proteins and its potential role in the proper assembly and/or encapsidation of the RNP complex within the maturing virions. In summary, our studies have revealed an unexpected and novel mechanism by which NCINIs block the replication of HIV. At the time of completion of our report, Jurado et al. published a study focused on the mechanistic characterization of allosteric HIV integrase inhibitors analogous to NCINIs. This independent study arrived at virtually identical conclusions, demonstrating a potent late-stage antiviral effect of ALLINIs due to their interference with proper virus assembly, leading to a block of reverse transcriptase in newly infected target cells. Similar to us, Jurado et al. linked this mechanism to the ability of ALLINIs to induce oligomerization of IN within HIV particles undergoing the maturation process. This remarkable consistency of both reports solidifies the current understanding of the antiviral effect of NCINIs/ALLINIs and underscores the continuing interest in further optimization and subsequent clinical development of these compounds as a novel class of antiretrovirals with a unique orthogonal mechanism of action. Among the HDAC family members, HDAC3 is unique in that it is expressed in the nucleus, Epoxomicin cytoplasm, or membrane, and it deacetylates histone and non-histone proteins such as NF-kB, myocyte enhancer factor 2, and Src kinase. Furthermore, recent studies have indicated that HDAC3 is associated with several diseases including cancer, inflammation, and neurodegenerative disorders. Therefore, TWS119 HDAC3-selective inhibitors are of great interest not only as tools for probing the biological functions of HDAC3, but also as candidate therapeutic agents with potentially few side effects. Although many efforts have been directed to the discovery of potent and selective HDAC inhibitors by numerous academic groups, as well as pharmaceutical companies, only a few HDAC3- selective inhibitors have been reported . For example, HDAC3 is selectively inhibited by compounds 1 and 2 , but their HDAC3-inhibitory activity and selectivity are insufficient for their development as candidate therapeutic agents. In addition, while this research was carried out, RGFP966, a novel HDAC3-selective inhibitor, was reported, although the details of the inhibitor are unclear.