Drug Information

Drug (ID: DG00578) and It's Reported Resistant Information

• Name: Tenofovir disoproxil fumarate
• Synonyms: Tenofovir Disoproxil Fumarate; 202138-50-9; Viread; Tenofovir DF; UNII-OTT9J7900I; OTT9J7900I; Tenofovir Disoproxil (fumarate); Tenofovir (Disoproxil Fumarate); GS-4331-05; CHEBI:63718; GSK-548470; 9-((R)-2-((bis(((isopropoxycarbonyl)oxy)methoxy)phosphinyl)methoxy)propyl)adenine fumarate; (R)-(((((1-(6-amino-9H-purin-9-yl)propan-2-yl)oxy)methyl)phosphoryl)bis(oxy))bis(methylene) diisopropyl dicarbonate fumarate; 2,4,6,8-Tetraoxa-5-phosphanonanedioic acid, 5-[[(1R)-2-(6-amino-9H-purin-9-yl)-1-methylethoxy]methyl]-, 1,9-bis(1-methylethyl) ester, 5-oxide, (2E)-2-butenedioate (1:1); Tenofovir Disoproxil Fumarate; (2E)-but-2-enedioic acid bis({[(propan-2-yloxy)carbonyl]oxy}methyl) {[(2R)-1-(6-amino-9H-purin-9-yl)propan-2-yl]oxy}methanephosphonate; [[(2R)-1-(6-aminopurin-9-yl)propan-2-yl]oxymethyl-(propan-2-yloxycarbonyloxymethoxy)phosphoryl]oxymethyl propan-2-yl carbonate;(E)-but-2-enedioic acid; HSDB 7165; Tenofovirdisoproxilfumarate; C19H30N5O10P.C4H4O4; Tenofovir Disoproxil Fumarate [USAN]; Virea; GS 4331-05; GSK548470; Viread (TN); PMPA-PRODRUG; tenofovir-disoproxil-fumarate; CHEMBL1486; SCHEMBL40021; Tenofoviri disoproxili fumaras; MLS004774141; GS-1278 Disoproxil Fumarate; SCHEMBL2670560; AOB5580; EX-A590; s1400; Tenofovir disoproxil fumarate- Bio-X; AKOS016340707; AKOS025149493; CCG-270300; CS-1346; GS-US-104-0321; KS-1246; 9-((R)-2-((Bis(((isopropoxycarbonyl)oxy)methoxy)phosphinyl)methoxy)propyl)adenine, fumarate; (R)-5-((2-(6-Amino-9H-purin-9-yl)-1-methylethoxy)methyl)-2,4,6,8-tetraoxa-5-phosphanonanedioic acid, bis(1-methylethyl) ester, 5-oxide, (E)-2-butenedioate (1:1); 9-((R)-2-((Bis(((isopropoxycarbonyl)oxy)methoxy)phosphinyl)methoxy)propyl)adenine fumarate (1:1); Bis(hydroxymethyl) (((R)-2-(6-amino-9H-purin-9-yl)-1-methylethoxy)methyl)phosphonate, bis(isopropyl carbonate) (ester), fumarate (1:1); BT164457; HY-13782; SMR003500786; Tenofovir disoproxil fumarate (JAN/USAN); BCP0726000258; AM20090676; V1698; GS-4331-05-; D01982; Tenofovir disoproxil fumarate, >=98% (HPLC); Q-201788; Q27132754; [[(1R)-2-(6-aminopurin-9-yl)-1-methyl-ethoxy]methyl-(isopropoxycarbonyloxymethoxy)phosphoryl]oxymethyl isopropyl carbonate; fumaric acid; 9-[(R)-2[[bis[[(isopropoxycarbonyl)oxy]methoxy]phosphinyl]methoxy]propyl]adenine fumarate (1:1); bis({[(propan-2-yloxy)carbonyl]oxy}methyl) ({[(2R)-1-(6-amino-9H-purin-9-yl)propan-2-yl]oxy}methyl)phosphonate (2E)-but-2-enedioate; Tenofovir disoproxil fumarate, Pharmaceutical Secondary Standard; Certified Reference Material
• Indication:
  In total 1 Indication(s)
  Discovery agent [ICD-11: N.A.]; Approved; [1]
• Drug Resistance Disease(s):
  Disease(s) with Resistance Information Validated by in-vivo Model for This Drug (1 diseases)
  Hepatitis B viral hepatitis [ICD-11: 1E51]; [1]
• Target: Human immunodeficiency virus Reverse transcriptase (HIV RT); POL_HV1B1; [1]
• Formula: C23H34N5O14P
• IsoSMILES: C[C@H](CN1C=NC2=C(N=CN=C21)N)OCP(=O)(OCOC(=O)OC(C)C)OCOC(=O)OC(C)C.C(=C/C(=O)O)\\C(=O)O
• InChI: 1S/C19H30N5O10P.C4H4O4/c1-12(2)33-18(25)28-9-31-35(27,32-10-29-19(26)34-13(3)4)11-30-14(5)6-24-8-23-15-16(20)21-7-22-17(15)24;5-3(6)1-2-4(7)8/h7-8,12-14H,6,9-11H2,1-5H3,(H2,20,21,22);1-2H,(H,5,6)(H,7,8)/b;2-1+/t14-;/m1./s1
• InChIKey: VCMJCVGFSROFHV-WZGZYPNHSA-N
• PubChem CID: 6398764
• ChEBI ID: CHEBI:63718
• TTD Drug ID: D0R3FP
• INTEDE ID: DR1554
• DrugBank ID: DB00300

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

Hepatitis B viral hepatitis [ICD-11: 1E51]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: HBV Polymerase/reverse transcriptase domain (HBV RT) [1]

• Molecule Alteration: Missense mutation; rtA181T+ rtA181V+ rtN236T
• Resistant Disease: Hepatitis B virus infection [ICD-11: 1E51.0]
• Experimental Note: Discovered Using In-vivo Testing Model
• Mechanism Description: The common LMV substitution for primary resistance involves the amino acid change rtM204V/I arising in the YMDD, a catalytic motif of pol. The compensatory change associated with rtM204V is at rtL180M, rtV173L and rtL80M. ADV resistance is characterized by rtN236T and/or rtA181V/T. ETV resistance tends to emerge in a stepwise manner with the rtS202I change occurring sequentially in viruses already bearing LMV resistance substitution (rtL180M plus rtM204V) mutations, although primary ETV resistance has been reported where these mutations have appeared simultaneously. For LdT, the year 2 resistance rates were 29% in HBeAg-positive and 11% in HBeAg-negative patients with the primary resistance mutation rtM204I. Secondary mutations associated with antiviral therapy, namely rtL80I/V and rtV173L plus rtL180M can also accompany this signature mutation in approximately 2-5% of cases. No definitive TDF-associated mutations have been described in treatment-naive patients taking TDF for up 5 years, but the selection of ADV-therapy associated resistance mutations, rtA181T/V and rtN236T, leads to reduced sensitivity to TDF when the patient is switched, and this has been described in both the clinical and virological setting.

References

• Ref 1: Hepatitis B antivirals and resistance .Curr Opin Virol. 2013 Oct;3(5):495-500. doi: 10.1016/j.coviro.2013.08.006. Epub 2013 Sep 7. 10.1016/j.coviro.2013.08.006