DT-Web

DB00879 - Emtricitabine


Identification
Name Emtricitabine
Accession Number DB00879 (APRD00226)
Type small molecule
Description Emtricitabine is a nucleoside reverse transcriptase inhibitor (NRTI) for the treatment of HIV infection in adults. Emtricitabine is an analogue of cytidine. The drug works by inhibiting reverse transcriptase, the enzyme that copies HIV RNA into new viral DNA.
Structure
MOL SDF PDB SMILES InChI
Categories (*)
Molecular Weight 247.247
Groups approved
Monoisotopic Weight 247.042690096
Pharmacology
Indication Indicated, in combination with other antiretroviral agents, for the treatment of HIV-1 infection in adults and for postexposure prophylaxis of HIV infection in health care workers and others exposed occupationally or nonoccupationally via percutaneous injury or mucous membrane or nonintact skin contact with blood, tissues, or other body fluids associated with risk for transmission of the virus.
Mechanism of action Emtricitabine works by inhibiting reverse transcriptase, the enzyme that copies HIV RNA into new viral DNA. Emtricitabine is a synthetic nucleoside analogue of cytidine. It is phosphorylated by cellular enzymes to form emtricitabine 5'-triphosphate, which is responsible for the inhibition of HIV-1 reverse transcriptase. It competes with the natural substrate deoxycytidine 5'-triphosphate and incorporates into nascent viral DNA, resulting in early chain termination. Therefore emtricitabine inhibits the activity of HIV-1 reverse transcriptase (RT) both by competing with the natural substrate deoxycytidine 5'-triphosphate and by its incorporation into viral DNA. By inhibiting HIV-1 reverse transcriptase, emtricitabine can help to lower the amount of HIV, or "viral load", in a patient's body and can indirectly increase the number of immune system cells (called T cells or CD4+ T-cells). Both of these changes are associated with healthier immune systems and decreased likelihood of serious illness.
Absorption Rapidly absorbed (mean absolute bioavailability of 93% for capsules, and 75% for solution). Food does not effect absorption.
Protein binding Very low (less than 4%)
Biotransformation Minimally transformed (13%), most appears unchanged in urine (86%). The biotransformation of emtricitabine includes oxidation of the thiol moiety to form the 3′-sulfoxide diastereomers (~ 9% of dose) and conjugation with glucuronic acid to form 2′-O-glucuronide (~ 4% of dose). In vitro studies indicate emtricitabine is not an inhibitor or cytochrome P450 enzymes.
Route of elimination The renal clearance of emtricitabine is greater than the estimated creatinine clearance, suggesting elimination by both glomerular filtration and active tubular secretion.
Toxicity Symptoms of overdose include serious liver problems (hepatotoxicity, with liver enlargement and fat in the liver called steatosis) or a lactic acidosis (buildup of an acid in the blood).
Affected organisms
  • Human Immunodeficiency Virus
Interactions
Drug Interactions
Drug Mechanism of interaction
Valganciclovir The adverse/toxic effects of reverse transcriptase inhibitors (nucleoside), such as Emtricitabine, may be enhanced by Valganciclovir. There is a risk of hematologic toxicity. Diligent monitoring during concomitant therapy is recommended.
Food Interactions
  • Take without regard to meals.

Targets


Reverse transcriptase
Name Reverse transcriptase
Gene Name Not Available
Pharmacological action yes
Actions inhibitor
References
  • Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. - Pubmed
  • Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. - Pubmed
  • Nirogi R, Bhyrapuneni G, Kandikere V, Mudigonda K, Komarneni P, Aleti R, Mukkanti K: Simultaneous quantification of a non-nucleoside reverse transcriptase inhibitor efavirenz, a nucleoside reverse transcriptase inhibitor emtricitabine and a nucleotide reverse transcriptase inhibitor tenofovir in plasma by liquid chromatography positive ion electrospray tandem mass spectrometry. Biomed Chromatogr. 2009 Apr;23(4):371-81. - Pubmed
  • Feng JY, Ly JK, Myrick F, Goodman D, White KL, Svarovskaia ES, Borroto-Esoda K, Miller MD: The triple combination of tenofovir, emtricitabine and efavirenz shows synergistic anti-HIV-1 activity in vitro: a mechanism of action study. Retrovirology. 2009 May 13;6:44. - Pubmed
  • Delahunty T, Bushman L, Robbins B, Fletcher CV: The simultaneous assay of tenofovir and emtricitabine in plasma using LC/MS/MS and isotopically labeled internal standards. J Chromatogr B Analyt Technol Biomed Life Sci. 2009 Jul 1;877(20-21):1907-14. Epub 2009 May 21. - Pubmed
  • Emtricitabine/tenofovir disoproxil fumarate. Drugs R D. 2004;5(3):160-1. - Pubmed
  • Goicoechea M, Best B: Efavirenz/emtricitabine/tenofovir disoproxil fumarate fixed-dose combination: first-line therapy for all? Expert Opin Pharmacother. 2007 Feb;8(3):371-82. - Pubmed
  • Perry CM: Emtricitabine/tenofovir disoproxil fumarate: in combination with a protease inhibitor in HIV-1 infection. Drugs. 2009;69(7):843-57. - Pubmed
  • Saag MS: Emtricitabine, a new antiretroviral agent with activity against HIV and hepatitis B virus. Clin Infect Dis. 2006 Jan 1;42(1):126-31. Epub 2005 Nov 23. - Pubmed
DTHybrid score Not Available

Enzymes


Deoxycytidine kinase
Name Deoxycytidine kinase
Gene Name DCK
Actions substrate
References
  • Bethell R, De Muys J, Lippens J, Richard A, Hamelin B, Ren C, Collins P: In vitro interactions between apricitabine and other deoxycytidine analogues. Antimicrob Agents Chemother. 2007 Aug;51(8):2948-53. Epub 2007 May 21. - Pubmed
DTHybrid score 0.4453

Predictions


Id Partner name Gene Name Score
603 DNA polymerase alpha catalytic subunit POLA1 0.1062
3690 Class B acid phosphatase precursor aphA 0.0952
360 Ribonucleoside-diphosphate reductase large subunit RRM1 0.0796
2222 Equilibrative nucleoside transporter 1 SLC29A1 0.0724
1064 DNA (cytosine-5)-methyltransferase 1 DNMT1 0.0636
6083 Deoxyguanosine kinase, mitochondrial DGUOK 0.0461
6171 Solute carrier family 28 member 3 SLC28A3 0.0457
3611 Cytidine deaminase cdd 0.0288
3707 Cytidine deaminase cdd 0.0288
4211 Cytidine deaminase CDA 0.0288
24 Thymidylate synthase TMP1 0.0246
359 Thymidylate synthase TYMS 0.0246
2626 Thymidylate synthase thyA 0.0246
2729 Thymidylate synthase thyA 0.0246
5352 Thymidylate synthase THYA 0.0246
1732 ATP-binding cassette sub-family G member 2 ABCG2 0.0231
702 UMP-CMP kinase CMPK1 0.0222
3957 Adenosine deaminase ADA 0.022
1043 Trifunctional purine biosynthetic protein adenosine-3 [Includes: Phosphoribosylamine--glycine ligase GART 0.0205
6148 Multidrug resistance-associated protein 7 ABCC10 0.0194
2287 Bifunctional purine biosynthesis protein PURH [Includes: Phosphoribosylaminoimidazolecarboxamide formyltransferase ATIC 0.0176
1830 5'-nucleotidase NT5E 0.0163
6144 Solute carrier family 22 member 2 SLC22A2 0.016
6145 Solute carrier family 22 member 1 SLC22A1 0.0153
125 DNA polymerase beta POLB 0.0153
6111 DNA polymerase epsilon subunit 4 POLE4 0.0131
6112 DNA polymerase epsilon subunit 3 POLE3 0.0131
6108 Ribonucleoside-diphosphate reductase subunit M2 B RRM2B 0.0131
6110 DNA polymerase epsilon subunit 2 POLE2 0.0131
6109 DNA polymerase epsilon catalytic subunit A POLE 0.0131
365 Dihydrofolate reductase DHFR 0.0131
2381 Dihydrofolate reductase DFR1 0.0131
2833 Dihydrofolate reductase Not Available 0.0131
2931 Dihydrofolate reductase folA 0.0131
3544 Dihydrofolate reductase folA 0.0131
3682 Dihydrofolate reductase folA 0.0131
6642 Dihydrofolate reductase folA 0.0131
6756 Dihydrofolate reductase dfrA 0.0131
4218 Ribonucleoside-diphosphate reductase M2 subunit RRM2 0.0102
342 P protein [Includes: DNA-directed DNA polymerase P 0.0099
612 P protein [Includes: DNA-directed DNA polymerase P 0.0099
1729 Solute carrier family 22 member 6 SLC22A6 0.0093
6031 Cytochrome P450 3A43 CYP3A43 0.0091
677 Choline-phosphate cytidylyltransferase A PCYT1A 0.0088
4512 Cytochrome P450 3A4 CYP3A4 0.0087
1588 Multidrug resistance protein 1 ABCB1 0.0081
5626 Nucleoside diphosphate kinase B NME2 0.0079
6143 Solute carrier family 22 member 7 SLC22A7 0.0071
5294 Nucleoside diphosphate kinase A NME1 0.007
277 Purine nucleoside phosphorylase PNP 0.0065
2870 Purine nucleoside phosphorylase punA 0.0065
2945 Purine nucleoside phosphorylase punA 0.0065
4659 Purine nucleoside phosphorylase TM_1596 0.0065
4825 Purine nucleoside phosphorylase TTHA1435 0.0065
6107 Cytochrome P450 3A7 CYP3A7 0.0055
4118 Cytochrome P450 3A5 CYP3A5 0.0052
4757 Cytochrome P450 2C9 CYP2C9 0.0047
1709 Canalicular multispecific organic anion transporter 2 ABCC3 0.0046
6147 Solute carrier family 22 member 3 SLC22A3 0.0046
4119 Cytochrome P450 2D6 CYP2D6 0.0046
2164 Multidrug resistance-associated protein 4 ABCC4 0.0044
862 Multidrug resistance-associated protein 1 ABCC1 0.004
1735 Canalicular multispecific organic anion transporter 1 ABCC2 0.0038
5287 Signaling protein Not Available 0.0021
5288 Shikimate kinase aroK 0.0021
5304 UPF0166 protein TM_0021 TM_0021 0.0021
5270 ATP-dependent Clp protease ATP-binding subunit clpX clpX 0.0021
5314 UPF0079 ATP-binding protein HI0065 HI_0065 0.0021
5259 Transcriptional regulator ntrC1 0.0021
6699 Transcriptional regulator Cgl2612 0.0021
5290 ATP-dependent hsl protease ATP-binding subunit hslU hslU 0.0021
5638 ATP-dependent hsl protease ATP-binding subunit hslU hslU 0.0021
3199 Phosphopantetheine adenylyltransferase coaD 0.0021
3543 Phosphopantetheine adenylyltransferase coaD 0.0021
3567 Phosphopantetheine adenylyltransferase coaD 0.0021
5289 Phosphopantetheine adenylyltransferase coaD 0.0021
2874 Nitrogenase iron protein 1 nifH1 0.0021
4346 Polynucleotide kinase pseT 0.0021
5293 Shikimate kinase 2 aroL 0.0021
5292 Putative partitioning protein TT_C1605 0.0021
5281 Plasmid segregation protein parM parM 0.0021
5305 Phosphoribosylaminoimidazole carboxylase ATPase subunit purK 0.0021
5299 D-alanine--D-alanine ligase ddl 0.0021
6598 D-alanine--D-alanine ligase ddl 0.0021
5276 Chromosomal replication initiator protein dnaA dnaA 0.0021
5266 Activator of hgdC 0.0021
4794 Phosphoenolpyruvate carboxykinase [ATP] pckA 0.0021
5283 D-alanine--D-alanine ligase B ddlB 0.0021
5275 Multidrug resistance ABC transporter ATP-binding and permease protein lmrA 0.0021
5308 Preprotein translocase secA 1 subunit secA1 0.0021
5315 Chaperone protein htpG htpG 0.0021
1549 Heat shock 70 kDa protein 1 HSPA1A 0.0021
5284 Large T antigen Not Available 0.0021
3777 ATP-dependent Clp protease ATP-binding subunit clpA clpA 0.0021
3982 Phosphoribosylformylglycinamidine synthase PFAS 0.0021
5261 Phosphoribosylformylglycinamidine synthase purL 0.0021
5277 Preprotein translocase subunit secA secA 0.0021
5291 Glycogen synthase 1 glgA1 0.0021
5264 DNA replication protein REP 0.0021
5285 Kinesin heavy chain KIF5B 0.0021
4106 Guanylate kinase GUK1 0.0016
4516 Guanylate kinase gmk 0.0016
413 Amidophosphoribosyltransferase PPAT 0.0016
2515 Amidophosphoribosyltransferase purF 0.0016
3714 Amidophosphoribosyltransferase purF 0.0016
6277 Heat shock cognate 71 kDa protein HSPA8 0.0016
3390 Aminoglycoside 3'-phosphotransferase aphA 0.0016
6029 Aminoglycoside 3'-phosphotransferase aphA1 0.0016
4837 Cag-alfa cag-alfa 0.0016
5646 Galactokinase GALK1 0.0016
5302 TrwB trwB 0.0016
4839 DNA polymerase III subunit tau dnaX 0.0016
4774 NTPase P4 Not Available 0.0016
4838 PMS1 protein homolog 2 PMS2 0.0016
5265 FtsH ftsH 0.0016
340 Apoptotic protease-activating factor 1 APAF1 0.0016
2270 Dephospho-CoA kinase coaE 0.0016
5189 Trimethylamine dehydrogenase tmd 0.0016
2284 Adenylate kinase adk 0.0016
2296 Adenylate kinase adk 0.0016
2311 Adenylate kinase adk 0.0016
2312 Adenylate kinase Not Available 0.0016
5295 2-keto-3-deoxy-gluconate kinase TT_P0036 0.0015
2751 Holliday junction ATP-dependent DNA helicase ruvB ruvB 0.0015
4755 Holliday junction ATP-dependent DNA helicase ruvB ruvB 0.0015
3470 Hypothetical protein MG245 homolog MPN_348 0.0015
3175 Glutamate--cysteine ligase gshA 0.0015
3426 Glutamine synthetase glnA 0.0015
3987 Glutamine synthetase GLUL 0.0015
5300 Antigen peptide transporter 1 TAP1 0.0015
2683 Mono-ADP-ribosyltransferase C3 C3 0.0015
2390 Nonsecretory ribonuclease RNASE2 0.0014
5312 Kinesin-like protein KIF1A KIF1A 0.0014
2282 Protein recA recA 0.0014
2315 Protein recA recA 0.0014
2332 Protein recA recA 0.0014
5263 Protein recA recA 0.0014
2922 Glycerol kinase glpK 0.0014
408 Riboflavin kinase RFK 0.0014
5271 Focal adhesion kinase 1 PTK2 0.0013
2615 Chemotaxis protein cheA cheA 0.0013
5278 Bifunctional 3'-phosphoadenosine 5'-phosphosulfate synthetase 1 PAPSS1 0.0013
6832 Serine/threonine-protein kinase SRPK2 SRPK2 0.0013
1881 Hexokinase-1 HK1 0.0013
2371 Pantothenate kinase coaA 0.0013
3669 Ribokinase rbsK 0.0013
2950 Inositol-trisphosphate 3-kinase A ITPKA 0.0012
2892 Acetylglutamate kinase argB 0.0012
3550 Acetylglutamate kinase argB 0.0012
4366 Riboflavin kinase/FMN adenylyltransferase TM_0857 0.0012
825 Arsenical pump-driving ATPase ASNA1 0.0012
3435 Arsenical pump-driving ATPase arsA 0.0012
137 FolC bifunctional protein [Includes: Folylpolyglutamate synthase folC 0.0012
2697 Uridine-cytidine kinase 2 UCK2 0.0012
6857 [Pyruvate dehydrogenase [lipoamide]] kinase isozyme 2, mitochondrial PDK2 0.0012
2727 S-adenosylmethionine synthetase metK 0.0012
201 Glutamate dehydrogenase 1, mitochondrial GLUD1 0.0011
788 Creatine kinase M-type CKM 0.0011
2817 Phosphoribosylglycinamide formyltransferase 2 purT 0.0011
6390 Sarcoplasmic/endoplasmic reticulum calcium ATPase 1 ATP2A1 0.0011
453 S-adenosylmethionine synthetase isoform type-1 MAT1A 0.0011
48 Pyridoxal kinase PDXK 0.0011
2251 Thymidylate kinase tmk 0.0011
2254 Thymidylate kinase DTYMK 0.0011
3522 Thymidylate kinase tmk 0.0011
61 2-amino-4-hydroxy-6-hydroxymethyldihydropteridine pyrophosphokinase folK 0.0011
2644 2-amino-4-hydroxy-6-hydroxymethyldihydropteridine pyrophosphokinase folK 0.0011
2710 2-amino-4-hydroxy-6-hydroxymethyldihydropteridine pyrophosphokinase folK 0.0011
207 Glutathione synthetase GSS 0.001
5269 Glutathione synthetase gshB 0.001
2334 Dethiobiotin synthetase bioD 0.001
6555 Dethiobiotin synthetase bioD 0.001
2184 Cystic fibrosis transmembrane conductance regulator CFTR 0.001
2091 Endoplasmin HSP90B1 0.001
2511 MAP kinase-activated protein kinase 2 MAPKAPK2 0.001
2317 UDP-N-acetylmuramoylalanine--D-glutamate ligase murD 0.001
509 Thymidine kinase TK 0.001
570 Thymidine kinase TK 0.001
2559 Thymidine kinase TK 0.001
3430 Thymidine kinase tdk 0.001
3518 Thymidine kinase TK 0.001
5301 Thymidine kinase tdk 0.001
5771 Thymidine kinase ORF36 0.001
7009 Thymidine kinase ORF36 0.001
6395 Myosin-14 MYH14 0.0009
1422 Serine/threonine-protein kinase 6 AURKA 0.0009
504 Mast/stem cell growth factor receptor KIT 0.0009
3379 Kinesin-like protein KIF11 KIF11 0.0009
3456 Heat shock protein HSP 90-beta HSP90AB1 0.0009
3822 Actin, alpha skeletal muscle ACTA1 0.0009
631 3-hydroxy-3-methylglutaryl-coenzyme A reductase HMGCR 0.0008
3387 3-hydroxy-3-methylglutaryl-coenzyme A reductase mvaA 0.0008
5682 Ribonuclease pancreatic RNASE1 0.0008
1721 Glycogen synthase kinase-3 beta GSK3B 0.0008
1939 Heat shock protein HSP 90-alpha HSP90AA1 0.0007
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