The unique mechanism of action in combination with the potential to be administered in combination with potent INSTIs, including raltegravir, elvitegravir, and dolutegravir, underlines the potential of LEDGINs for future HIV therapy. Vortioxetine (Lu AA21004) hydrobromide Integrase plays an important role in HIV infections by putting the reverse transcribed viral genome to the genome of infected cells. Integration occurs in infected cells following two distinct steps catalyzed by IN: 3 processing and strand transfer. 3 P occurs in the cytoplasm just after reverse transcription, it generates nucleophilic 3 hydroxyl adenosyl viral DNA ends, that are required for ST. Subsequent nuclear import of the preintegration processes, ST joins the viral 3 hydroxyl DNA ends to a host chromosome. Integration is finalized by cellular enzymes by cleaving the viral DNA 5 overhang and filling the space left between cellular and viral DNA. Raltegravir is highly active against recombinant IN and is one of the course of the IN strand exchange inhibitors that selectivity restrict ST over 3 P. The U. S. Food and Drug Administration approval of raltegravir for skilled Ribonucleotide patients, and more recently for naive patients, has dramatically influenced AIDS treatment. However, clinical resistance to RAL exists due to mutations in IN. Biochemical characterization of recombinant mutant IN enzymes demonstrated that RAL resistance involves among three major mutations: Y143R, G140S Q148H, and N155H. Current determination of the prototype foamy virus IN crystal structures in the presence of viral DNA and INSTIs has provided insights in to the active site of IN. These houses show that INSTIs behave as interfacial HDAC2 inhibitor inhibitors by developing a system of molecular interactions with IN, its viral DNA substrate and the metal ion co-factors. These structures revealed why elvitegravir works well from the RAL certain mutation Y143R. The oxadiazole moiety of RAL participates in a stacking interaction with the tyrosine 212 aromatic ring of PFV IN. This residue corresponds to Y143 in HIV 1 IN. Inhibitors missing this oxadiazole moiety, such as EVG, remain active from the Y143R IN mutant. However, the RAL resistance mutants N155H and G140S Q148H reduce the vulnerability of DIRECTLY into EVG. Merck & Co. Is promoting newer INSTIs, including MK 0536, with improved resistance profile and favorable pharmacokinetics. We synthesized this compound to examine and compare its efficacy with RAL against RAL resistant IN mutants in bio-chemical and viral replication assays. We also took advantage of the recently resolved company crystal structure of MK 0536 bound for the PFV IN active site to know the activity of MK 0536 against RAL resistance mutants and to design its binding to wild type and RAL resilient HIV 1 IN minerals. MK 0536 was synthesized based on known processes and raltegravir was purified as previously reported.