MK-2048 is the Merck & Co. designation for a molecule in its pre-clinical drug discovery portfolio that is an integrase inhibitor-class of agent selected for development as a preventative treatment against HIV infection.[1] Its second generation integrase design was hypothesized to be superior to the first available integrase inhibitor, raltegravir, in that "MK-2048 has a dissociation half-life of 32 hours on wild-type integrase—more than four times that of raltegravir",[1][2] and its dissociation half-life against the important HIV integrase mutant N155H was on the same order of magnitude as that of raltegravir against wild-type virus. These findings led Merck representatives to suggest the possibility of "reduced susceptibility to resistance mutations" for the second generation drug.[1] MK-2048 has been investigated for use as part of a pre-exposure prophylaxis (PrEP) approach to the treatment of HIV infection;[3] however, the results of a 2015-2016 placebo-controlled human clinical trial[4] indicated no observed correlation between tissue-associated VCV and/or MK-2048 and the inhibition of HIV infection, limiting expectations for this compound's efficacy for such applications.[5] At the time of these reports, there was no indication of the time by which "MK-2048, or related compounds, [would] be ready for clinical trials".[1]
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| ECHA InfoCard | 100.233.568 |
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| Formula | C21H21ClFN5O4 |
| Molar mass | 461.88 g·mol−1 |
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References
edit- ^ a b c d Mascolini M (April 2009). Conference Reports for NATAP: Merck Offers Unique Perspective on Second-Generation Integrase Inhibitor. 10th International Workshop on Clinical Pharmacology of HIV Therapy. Amsterdam]: NATAP.org. Archived from the original on June 4, 2017. Retrieved November 8, 2009.
- ^ Grobler JA, McKenna PM, Ly S, Stillmock K, Bahnck C, Danovich RM, et al. (April 2009). Presentation, Abstract O-10: Functionally Irreversible Inhibition of Integration by Slowly Dissociating Strand Transfer Inhibitors. 10th International Workshop on Clinical Pharmacology of HIV Therapy. Amsterdam]: NATAP.org.
- ^ Alcorn K (April 28, 2009). "Ralvetgravir Shows Potential for use as PrEP Drug". AIDSmap.com. Archived from the original on January 3, 2010. Retrieved November 8, 2009.
- ^ Clinical trial number NCT02356302 for "Safety and Pharmacokinetics of Intravaginal Rings Containing Vicriviroc (MK-4176) and/or MK-2048" at ClinicalTrials.gov
- ^ Hoesley CJ, Chen BA, Anderson PL, Dezzutti CS, Strizki J, Sprinkle C, et al. (March 2019). "Phase 1 Safety and Pharmacokinetics Study of MK-2048/Vicriviroc (MK-4176)/MK-2048A Intravaginal Rings". Clinical Infectious Diseases. 68 (7): 1136–1143. doi:10.1093/cid/ciy653. PMC 6424075. PMID 30289435.
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