Drug Information

Drug (ID: DG01286) and It's Reported Resistant Information

• Name: MK-1439
• Synonyms: Doravirine; 1338225-97-0; MK-1439; Pifeltro; 3-chloro-5-[1-[(4-methyl-5-oxo-1H-1,2,4-triazol-3-yl)methyl]-2-oxo-4-(trifluoromethyl)pyridin-3-yl]oxybenzonitrile; MK1439; UNII-913P6LK81M; 3-Chloro-5-((1-((4-methyl-5-oxo-4,5-dihydro-1H-1,2,4-triazol-3-yl)methyl)-2-oxo-4-(trifluoromethyl)-1,2-dihydropyridin-3-yl)oxy)benzonitrile; Doravirine (MK-1439); 913P6LK81M; 3-Chloro-5-({1-[(4-Methyl-5-Oxo-4,5-Dihydro-1h-1,2,4-Triazol-3-Yl)methyl]-2-Oxo-4-(Trifluoromethyl)-1,2-Dihydropyridin-3-Yl}oxy)benzonitrile; Doravirine [USAN:INN]; 4ncg; Pifeltro (TN); MK 1439; Doravirine, MK-1439; Doravirine; MK-1439; MK-1439(Doravirine); C17H11ClF3N5O3; Doravirine (JAN/USAN/INN); Mk-1439a; SCHEMBL2509885; CHEMBL2364608; DTXSID30158386; AMY16781; BCP02296; EX-A1968; BDBM50508293; MFCD22417167; s6492; ZINC72317283; AKOS030528603; CS-5924; DB12301; SB17104; NCGC00508866-01; AC-33637; HY-16767; DB-091410; D10624; F53303; A856128; Q6885419; S900006160; 2KW; 3-chloro-5-[[1-[(4-methyl-5-oxo-1H-1,2,4-triazol-3-yl)methyl]-2-oxo-4-(trifluoromethyl)-3-pyridyl]oxy]benzonitrile; Benzonitrile, 3-chloro-5-((1-((4,5-dihydro-4-methyl-5-oxo-1H-1,2,4-triazol-3-yl)methyl)-1,2-dihydro-2-oxo-4-(trifluoromethyl)-3-pyridinyl)oxy)-
• Indication:
  In total 2 Indication(s)
  Human immunodeficiency virus infection [ICD-11: 1C60-1C62]; Approved; [1]
  Human immunodeficiency virus infection [ICD-11: 1C60-1C62]; Approved; [1]
• Drug Resistance Disease(s):
  Disease(s) with Clinically Reported Resistance for This Drug (1 diseases)
  HIV infection [ICD-11: 1C62]; [1]
• Target: Human immunodeficiency virus Reverse transcriptase (HIV RT); POL_HV1B1; [1]
• Formula: C17H11ClF3N5O3
• IsoSMILES: CN1C(=NNC1=O)CN2C=CC(=C(C2=O)OC3=CC(=CC(=C3)C#N)Cl)C(F)(F)F
• InChI: 1S/C17H11ClF3N5O3/c1-25-13(23-24-16(25)28)8-26-3-2-12(17(19,20)21)14(15(26)27)29-11-5-9(7-22)4-10(18)6-11/h2-6H,8H2,1H3,(H,24,28)
• InChIKey: ZIAOVIPSKUPPQW-UHFFFAOYSA-N
• PubChem CID: 58460047
• TTD Drug ID: D0R0TS
• INTEDE ID: DR0533

Type(s) of Resistant Mechanism of This Drug

  ADTT: Aberration of the Drug's Therapeutic Target

Drug Resistance Data Categorized by Their Corresponding Diseases

ICD-01: Infectious/parasitic diseases

HIV infection [ICD-11: 1C62]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: HIV1 Reverse transcriptase (HIV1 RT) [1]

• Molecule Alteration: Missense mutation; p.Y188L
• Resistant Disease: Human immunodeficiency virus infection [ICD-11: 1C62.0]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: AIP KO MEF cells; Skin; Mus musculus (Mouse); CVCL_UJ02
• In Vitro Model: MT4 cells; Umbilical cord blood; Homo sapiens (Human); CVCL_2632
• Experiment for Molecule Alteration: PCR
• Mechanism Description: The cyanochlorophenol moiety forms pai-pai stacking with Y188, and the Y188L substitution eliminates the pai-pai interactions and creates a clash with DOR; thus, the Y188L substitution confers significant resistance to DOR, suggesting that the pai-pai interactions between the residues are crucial for the binding of DOR to RT.

References

• Ref 1: In vitro resistance selection with doravirine (MK-1439), a novel nonnucleoside reverse transcriptase inhibitor with distinct mutation development pathways .Antimicrob Agents Chemother. 2015 Jan;59(1):590-8. doi: 10.1128/AAC.04201-14. Epub 2014 Nov 10. 10.1128/AAC.04201-14