| Drug General Information |
| Drug ID |
D0A4IJ
|
| Drug Name |
Abacavir |
|
| Synonyms |
Trizivir; Ziagen; Abacavir [INN]; Abacavir (INN); Ziagen (TN); Ziagen (TM)(*Succinate salt*); [(1S,4R)-4-[2-amino-6-(cyclopropylamino)purin-9-yl]cyclopent-2-en-1-yl]methanol; {(1S-cis)-4-[2-amino-6-(cyclopropylamino)-9H-purin-9-yl]cyclopent-2-en-1-yl}methanol; (+/-)-4-[2-Amino-6-(cyclopropylamino)-9H-purin-9-yl]-2-cyclopentene-1-methanol; (+/-)-Abacavir; (1S,4R)-4-[2-Amino-6-(cyclopropylamino)-9H-purin-9-yl]-2-cyclopentene-1-methanol; ABC |
| Drug Type |
Small molecular drug |
| Therapeutic Class |
Anti-HIV Agents |
| Company |
GlaxoSmithKline |
| Structure |
|
| Drug Resistance Mutations |
| Target Name |
HIV Nucleoside reverse transcriptase |
Target Info |
| Uniprot ID |
POL_HV1B1(600-1159) |
| Species |
Human immunodeficiency virus type 1 (HIV-1) |
| Reference Sequence |
PISPIETVPVKLKPGMDGPKVKQWPLTEEKIKALVEICTEMEKEGKISKIGPENPYNTPV
FAIKKKDSTKWRKLVDFRELNKRTQDFWEVQLGIPHPAGLKKKKSVTVLDVGDAYFSVPL
DEDFRKYTAFTIPSINNETPGIRYQYNVLPQGWKGSPAIFQSSMTKILEPFKKQNPDIVI
YQYMDDLYVGSDLEIGQHRTKIEELRQHLLRWGLTTPDKKHQKEPPFLWMGYELHPDKWT
VQPIVLPEKDSWTVNDIQKLVGKLNWASQIYPGIKVRQLCKLLRGTKALTEVIPLTEEAE
LELAENREILKEPVHGVYYDPSKDLIAEIQKQGQGQWTYQIYQEPFKNLKTGKYARMRGA
HTNDVKQLTEAVQKITTESIVIWGKTPKFKLPIQKETWETWWTEYWQATWIPEWEFVNTP
PLVKLWYQLEKEPIVGAETFYVDGAANRETKLGKAGYVTN [Human immunodefici
ency virus type 1 (HIV-1)]
|
| Targeted Disease |
HIV infection |
| Drug Resistance Mutations |
| Mutation info |
Missense: L74I |
[1] |
| Mutation Frequency |
3-20% of the samples |
| Level of Resistance |
Reduce susceptibility to Abacavir |
|
| Mutation info |
Missense: K65R |
[2] |
| Level of Resistance |
Reduce ABC susceptibility 2 fold |
|
| Mutation info |
Missense: Y115F |
[3] |
| Level of Resistance |
Reduce ABC susceptibility 3 fold |
|
| Mutation info |
Missense: K65N |
[4], [5], [6] |
| Level of Resistance |
Reduce susceptibility to ABC |
|
| Mutation info |
Missense: L74V |
[7], [8], [9] |
| Level of Resistance |
Intermediate resistance |
|
| Mutation info |
Missense: K70E |
[10], [11] |
| Level of Resistance |
Low-level resistance |
|
| Mutation info |
Missense: K70G |
[10], [11] |
| Level of Resistance |
Low-level resistance |
|
| Mutation info |
Missense: K70N |
[10], [11] |
| Level of Resistance |
Low-level resistance |
|
| Mutation info |
Missense: K70Q |
[10], [11] |
| Level of Resistance |
Low-level resistance |
|
| Mutation info |
Missense: K70S |
[10], [11] |
| Level of Resistance |
Low-level resistance |
|
| Mutation info |
Missense: K70T |
[10], [11] |
| Level of Resistance |
Low-level resistance |
|
| Mutation info |
Missense: M184I |
[10], [11] |
| Level of Resistance |
Low-level resistance |
|
| Mutation info |
Missense: M184V |
[10], [11] |
| Level of Resistance |
Low-level resistance |
|
| Mutation info |
Missense: M41L |
[10], [11] |
|
| Mutation info |
Missense: Q151L |
[10], [11] |
| Level of Resistance |
Intermediate resistance |
|
| Mutation info |
Missense: Q151M |
[10], [11] |
| Level of Resistance |
Confer high-level resistance to ABC |
|
| Mutation info |
Missense: T210W |
[10], [11] |
|
| Mutation info |
Missense: T215F |
[10], [11] |
|
| Mutation info |
Missense: T215Y |
[10], [11] |
|
| Target Name |
HIV Non-Nucleoside reverse transcriptase |
Target Info |
| Uniprot ID |
POL_HV1B1(600-1159) |
| Species |
Human immunodeficiency virus type 1 (HIV-1) |
| Reference Sequence |
PISPIETVPVKLKPGMDGPKVKQWPLTEEKIKALVEICTEMEKEGKISKIGPENPYNTPV
FAIKKKDSTKWRKLVDFRELNKRTQDFWEVQLGIPHPAGLKKKKSVTVLDVGDAYFSVPL
DEDFRKYTAFTIPSINNETPGIRYQYNVLPQGWKGSPAIFQSSMTKILEPFKKQNPDIVI
YQYMDDLYVGSDLEIGQHRTKIEELRQHLLRWGLTTPDKKHQKEPPFLWMGYELHPDKWT
VQPIVLPEKDSWTVNDIQKLVGKLNWASQIYPGIKVRQLCKLLRGTKALTEVIPLTEEAE
LELAENREILKEPVHGVYYDPSKDLIAEIQKQGQGQWTYQIYQEPFKNLKTGKYARMRGA
HTNDVKQLTEAVQKITTESIVIWGKTPKFKLPIQKETWETWWTEYWQATWIPEWEFVNTP
PLVKLWYQLEKEPIVGAETFYVDGAANRETKLGKAGYVTNKGRQKVVPLTNTTNQKTELQ
AIYLALQDSGLEVNIVTDSQYALGIIQAQPDKSESELVNQIIEQLIKKEKVYLAWVPAHK
GIGGNEQVDKLVSAGIRKIL [Human immunodeficiency virus type 1 (H
IV-1)]
|
| Targeted Disease |
HIV infection |
| Drug Resistance Mutations |
| Mutation info |
Deletion: D67 |
[10], [11] |
| Level of Resistance |
Intermediate resistance |
|
| Mutation info |
Missense: D67E/G/N + K70R + M184I/V + K219E/N/Q/R |
[10], [11] |
| Level of Resistance |
Low-level resistance |
|
| Mutation info |
Deletion: K70 |
[10], [11] |
| Level of Resistance |
Low-level resistance |
|
| Mutation info |
Missense: L74I/V + M184I/V |
[10], [11] |
| Level of Resistance |
Low-level resistance |
|
| Mutation info |
Missense: M41L + T215F/Y |
[10], [11] |
| Level of Resistance |
Low-level resistance |
|
| Mutation info |
Deletion: S68 |
[10], [11] |
| Level of Resistance |
Low-level resistance |
|
| Mutation info |
Insertion: T69 |
[10], [11] |
| Level of Resistance |
Low-level resistance |
|
| Mutation info |
Deletion: T69 |
[10], [11] |
| Level of Resistance |
Low-level resistance |
|
| References |
| REF 1 |
Mechanisms of anti-retroviral drug resistance: implications for novel drug discovery and development. Infect Disord Drug Targets. 2013 Oct;13(5):330-6.
|
| REF 2 |
In vitro selection and characterization of HIV-1 with reduced susceptibility to PMPA. Antivir Ther. 1999;4(2):87-94.
|
| REF 3 |
Combination of mutations in human immunodeficiency virus type 1 reverse transcriptase required for resistance to the carbocyclic nucleoside 1592U89. Antimicrob Agents Chemother. 1997 May;41(5):1094-8.
|
| REF 4 |
A rare HIV reverse transcriptase mutation, K65N, confers reduced susceptibility to tenofovir, lamivudine and didanosine. AIDS. 2006 Mar 21;20(5):787-9.
|
| REF 5 |
In vitro human immunodeficiency virus type 1 resistance selections with combinations of tenofovir and emtricitabine or abacavir and lamivudine. Antimicrob Agents Chemother. 2006 Dec;50(12):4087-95.
|
| REF 6 |
Reverse transcriptase mutation K65N confers a decreased replication capacity to HIV-1 in comparison to K65R due to a decreased RT processivity. Virology. 2011 May 25;414(1):34-41.
|
| REF 7 |
Selection of L74V mutation in reverse transcriptase of HIV-1 subtype D by a tenofovir DF-lamivudine based regimen. AIDS. 2007 Nov 30;21(18):2551-2.
|
| REF 8 |
Trends in Genotypic HIV-1 Antiretroviral Resistance between 2006 and 2012 in South African Patients Receiving First- and Second-Line Antiretroviral Treatment Regimens. PLoS One. 2013 Jun 26;8(6):e67188.
|
| REF 9 |
HIV-1 Drug Resistance Mutations: Potential Applications for Point-of-Care Genotypic Resistance Testing. PLoS One. 2015 Dec 30;10(12):e0145772.
|
| REF 10 |
The HIVdb system for HIV-1 genotypic resistance interpretation. Intervirology. 2012;55(2):98-101.
|
| REF 11 |
Tackling the problem of HIV drug resistance. Postepy Biochem. 2016;62(3):273-279.
|
