MK-2048 

MK-2048 is a potent inhibitor of integrase and INR263K with IC50 of 2.6 nM and 1.5 nM, respectively. IC50 Value: 2.6 nM for HIV Integrase Target: HIV Integrase MK-2048 is a second generation integrase inhibitor, intended to be used against HIV infection. MK-2048 inhibits subtype B and subtype C integrase activities. MK-2048 inhibits R263K mutants slightly more effectively than G118R mutants. MK-2048 inhibits S217H intasome and, by contrast, MK-2048 remains fully active against the N224H intasome. MK-2048 displays substantially lower dissociation rates compared with raltegravir, another integrase inhibitor. MK-2048 is active against viruses resistant to RAL and EVG. MK-2048 exposure leads to the selection of G118R as a possible novel resistance mutation after 19 weeks. MK-2048, with continued pressure, subsequently leads to an additional substitution, at position E138K, after 29 weeks, within the IN gene. Although the G118R mutation alone confers only slight resistance to MK-2048 but not to RAL or EVG, its presence arouses a dramatic reduction in viral replication capacity compared to wild-type NL4-3. E138K both partially restores viral replication capacity and also contributes to increased levels of resistance against MK-2048.

461.87

C₂₁H₂₁ClFN₅O₄

869901-69-9

Solid

Light yellow to yellow

FC1=C(Cl)C=C(CN2C(C(C(O)=C3N4[C@@H](C)CN(CC)C3=O)=C4C(C(NC)=O)=N2)=O)C=C1

Room temperature in continental US; may vary elsewhere.

• [1]. L. Van Wesenbeeck, E. Rondelez, M. Feyaerts, et al. Cross-Resistance Profile Determination of Two Second-Generation HIV-1 Integrase Inhibitors Using a Panel of Recombinant Viruses Derived from Raltegravir-Treated Clinical Isolates .Antimicrob. Agents Chemother. 2011, 55 (1): 321-325

  [2]. Muhammad Esa Seegulam, Lee Ratner. Integrase Inhibitors Effective against Human T-Cell Leukemia Virus Type 1. Antimicrob. Agents Chemother. 2011, 55 (5): 2011-2017

  [3]. Tamara Bar-Magen1, Richard D. Sloan1, Daniel A. Donahue1, et al. Identification of Novel Mutations Responsible for Resistance to MK-2048, a Second-Generation HIV-1 Integrase Inhibitor. J. Virol. 2010, 84(18): 9210-9216

  [4]. Laith Q Al-Mawsawi, Rasha I Al-Safi, Nouri Neamati. Anti-infectives Clinical progress of HIV-1 integrase inhibitors. 2008, 13(2): Pages 213-225

  [5]. Al-Mawsawi LQ, Al-Safi RI, Neamati N. Anti-infectives: clinical progress of HIV-1 integrase inhibitors. Expert Opin Emerg Drugs. 2008 Jun;13(2):213-25.  [Content Brief]