MK-2048
MK-2048
Clinical data
ATC code
  • none
Legal status
Legal status
Identifiers
  • (6S)-2-[(3-chloro-4-fluorophenyl)methyl]-8-ethyl-9-hydroxy-N,6-dimethyl-1,10-dioxo-6,7-dihydropyrazino[3,4]pyrrolo[3,4-b]pyridazine-4-carboxamide
CAS Number
PubChem CID
ChemSpider
UNII
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard100.233.568 Edit this at Wikidata
Chemical and physical data
FormulaC21H21ClFN5O4
Molar mass461.88 g·mol−1
3D model (JSmol)
  • CCN1CC(N2C3=C(C(=O)C2=C1O)C(=O)N(N=C3C(=O)NC)CC4=CC(=C(C=C4)F)Cl)C
  • InChI=1S/C21H21ClFN5O4/c1-4-26-8-10(2)28-16-14(18(29)17(28)21(26)32)20(31)27(25-15(16)19(30)24-3)9-11-5-6-13(23)12(22)7-11/h5-7,10,32H,4,8-9H2,1-3H3,(H,24,30)/t10-/m0/s1
  • Key:IOYLKNABOQYKKY-JTQLQIEISA-N
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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]

References

  1. ^ 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. Retrieved November 8, 2009.
  2. ^ 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.
  3. ^ 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.
  4. ^ Clinical trial number NCT02356302 for "Safety and Pharmacokinetics of Intravaginal Rings Containing Vicriviroc (MK-4176) and/or MK-2048" at ClinicalTrials.gov
  5. ^ 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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