In prostate cancer cell lines, abacavir (15 and 150 μM, 0-120 hours) slows cell growth, modifies LINE-1 mRNA expression, promotes senescence, and changes cell cycle progression [1]. Cell migration is greatly reduced and cell invasion is inhibited by abacavir (15 and 150 μM, 18 hours) [1]. Adipocyte apoptosis is induced by abacavir [4].

Dose-dependently, abacavir (100 and 200 mg/kg, PO; 4 hours) increases thrombosis [2]. In mice with high-risk medulloblastoma, abacavir (50 mg/kg/d; intraperitoneal injection; 14 days) and decitabine (0.1 mg/kg/d) can increase survival rates [3].

Cell proliferation assay [1]
Cell Types: PC3, LNCaP and WI-38
Tested Concentrations: 15 and 150 μM
Incubation Duration: 0, 24, 48, 72 and 96 h
Experimental Results: Dose-dependent growth inhibition was shown for PC3 and LNCaP.

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Cell cycle analysis [1]
Cell Types: PC3 and LNCaP
Tested Concentrations: 150 μM
Incubation Duration: 0, 18, 24, 48, 72, 96 and 120 h
Experimental Results: Caused a large accumulation of S phase cells in PC3 and LNCaP cells, and in An increase in G2/M phase was observed in PC3 cells.

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Cell migration assay[1]
Cell Types: PC3 and LNCaP
Tested Concentrations: 15 and 150 μM
Incubation Duration: 18 hrs (hours)
Experimental Results: Significant reduction in cell migration.

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Cell invasion assay[1]
Cell Types: PC3 and LNCaP
Tested Concentrations: 15 and 150 μM
Incubation Duration: 18 hrs (hours)
Experimental Results: Significant inhibition of cell invasion.

Animal/Disease Models: Male mouse (9 weeks old, 22-30 g) - wild type (WT) C57BL/6 or homozygous knockout (P2rx7 KO, B6.129P2-P2rx7tm1Gab/J) [2]
Doses: 2.5, 5 and 7.5 μg/mL, 100 μL, or 100 and 200 mg/kg
Route of Administration: Intrascrotal or oral administration over 4 hrs (hrs (hours))
Experimental Results: Dose-dependent promotion of thrombosis.

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Animal/Disease Models: NSGTM mice, patient-derived xenograft (PDX) cells of non-WNT/non-SHH, group 3 and SHH/TP53 mutant medulloblastoma [3]
Doses: 50 mg/kg/d, 0.1 mg/kg /d Decitabine
Route of Administration: intraperitoneal (ip) injection, one time/day for 14 days
Experimental Results: Inhibited tumor growth and improved mouse survival.

Absorption, Distribution and Excretion
Rapid and extensive after oral administration (83% bioavailability, tablet). When a 300 mg tablet is given twice daily to subjects, the peak plasma concentration (Cmax) was 3.0 ± 0.89 mcg/mL and the area under the curve (AUC 0-12 hours) was 6.02 ± 1.73 mcg•hr/mL.
Elimination of abacavir was quantified in a mass balance study following administration of a 600-mg dose of 14C-abacavir: 99% of the radioactivity was recovered, 1.2% was excreted in the urine as abacavir, 30% as the 5′-carboxylic acid metabolite, 36% as the 5′-glucuronide metabolite, and 15% as unidentified minor metabolites in the urine. Fecal elimination accounted for 16% of the dose. Renal excretion of unchanged abacavir is a minor route of elimination in humans.
0.86 ± 0.15 L/kg [IV administration]
0.80 ± 0.24 L/hr/kg [asymptomatic, HIV-1-infected adult patients receiving single (IV dose of 150 mg]

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Metabolism / Metabolites
Hepatic, by alcohol dehydrogenase and glucuronosyltransferase to a 5′-carboxylic acid metabolite and 5′-glucuronide metabolite, respectively. These metabolites have no antiviral activity. Abacavir is not significantly metabolized by cytochrome P450 enzymes.

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Biological Half-Life
1.54 ± 0.63 hours

Hepatotoxicity
Elevations in serum aminotransferase levels above 5 times the upper limit of normal occur in up to 6% of patients on abacavir. These elevations are usually mild, transient and do not require dose adjustment. Clinically apparent hepatotoxicity is rare, but isolated cases [usually anicteric] have been published. The liver injury usually arises in the context of abacavir hypersensitivity syndrome and may be overshadowed by the allergic syndromes of fever, rash and fatigue. The onset is usually within 1 to 3 months of starting abacavir. The serum enzyme pattern can be hepatocellular or cholestatic. Patients typically recover rapidly within 4 weeks of stopping therapy.
Likelihood score: C (probable cause of clinically apparent liver injury).

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Effects During Pregnancy and Lactation
◉ Summary of Use during Lactation
Abacavir appears in breastmilk in small quantities. Very little information is available on the safety of its use during breastfeeding. Achieving and maintaining viral suppression with antiretroviral therapy decreases breastfeeding transmission risk to less than 1%, but not zero. Individuals with HIV who are on antiretroviral therapy with a sustained undetectable viral load and who choose to breastfeed should be supported in this decision. If a viral load is not suppressed, banked pasteurized donor milk or formula is recommended.
◉ Effects in Breastfed Infants
An HIV-positive mother took a combination tablet containing dolutegravir 50 mg, abacavir sulfate 600 mg and lamivudine 300 mg (Triumeq) once daily. Her infant was exclusively breastfed for about 30 weeks and partially breastfed for about 20 weeks more. No obvious side effects were noted.
◉ Effects on Lactation and Breastmilk
Gynecomastia has been reported among men receiving highly active antiretroviral therapy. Gynecomastia is unilateral initially, but progresses to bilateral in about half of cases. No alterations in serum prolactin were noted and spontaneous resolution usually occurred within one year, even with continuation of the regimen. Some case reports and in vitro studies have suggested that protease inhibitors might cause hyperprolactinemia and galactorrhea in some male patients, although this has been disputed. The relevance of these findings to nursing mothers is not known. The prolactin level in a mother with established lactation may not affect her ability to breastfeed.

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Protein Binding
Moderate (approximately 50%). Binding of abacavir to plasma protein was independent of concentration.

[1]. The reverse transcription inhibitor abacavir shows anticancer activity in prostate cancer cell lines. PLoS One. 2010 Dec 3;5(12):e14221.

[2]. Abacavir Induces Arterial Thrombosis in a Murine Model. J Infect Dis. 2018 Jun 20;218(2):228-233.

[3]. Enhanced Survival of High-Risk Medulloblastoma-Bearing Mice after Multimodal Treatment with Radiotherapy, Decitabine, and Abacavir. Int J Mol Sci. 2022 Mar 30;23(7):3815.

[4]. Improvements in lipoatrophy, mitochondrial DNA levels and fat apoptosis after replacing stavudine with abacavir or zidovudine. AIDS. 2005 Jan 3;19(1):15-23.

Abacavir is a 2,6-diaminopurine that is (1S)-cyclopent-2-en-1-ylmethanol in which the pro-R hydrogen at the 4-position is substituted by a 2-amino-6-(cyclopropylamino)-9H-purin-9-yl group. A nucleoside analogue reverse transcriptase inhibitor (NRTI) with antiretroviral activity against HIV, it is used (particularly as the sulfate) with other antiretrovirals in combination therapy of HIV infection. It has a role as a HIV-1 reverse transcriptase inhibitor, an antiviral drug and a drug allergen.
Abacavir (brand name: Ziagen) is a prescription medicine approved by the U.S. Food and Drug Administration (FDA) for the treatment of HIV infection in adults, children, and infants. Abacavir is always used in combination with other HIV medicines. 
Abacavir (ABC) is a powerful nucleoside analog reverse transcriptase inhibitor (NRTI) used to treat HIV and AIDS. Chemically, it is a synthetic carbocyclic nucleoside and is the enantiomer with 1S, 4R absolute configuration on the cyclopentene ring. In vivo, abacavir sulfate dissociates to its free base, abacavir.
Abacavir is a Human Immunodeficiency Virus Nucleoside Analog Reverse Transcriptase Inhibitor. The mechanism of action of abacavir is as a Nucleoside Reverse Transcriptase Inhibitor, and Cytochrome P450 1A1 Inhibitor.
Abacavir sulfate is a nucleoside analogue and reverse transcriptase inhibitor which is used in combination with other agents in the therapy of the human immunodeficiency virus (HIV) infection and the acquired immunodeficiency syndrome (AIDS). Abacavir is a rare cause of clinically apparent drug induced liver injury.
Abacavir is a nucleoside reverse transcriptase inhibitor analog of guanosine. This agent decreases HIV viral loads, retards or prevents the damage to the immune system, and reduces the risk of developing AIDS.

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Drug Indication
Abacavir is indicated in combination with other anti-retroviral agents for the treatment of HIV-1 infection. It is available in a combination product alongside [dolutegravir] and [lamivudine] for the treatment of adult and pediatric patients with HIV-1 who weigh ≥10 kg.
FDA Label
Ziagen is indicated in antiretroviral combination therapy for the treatment of Human Immunodeficiency Virus (HIV) infection in adults, adolescents and children. The demonstration of the benefit of Ziagen is mainly based on results of studies performed with a twice daily regimen, in treatment-naïve adult patients on combination therapy. Before initiating treatment with abacavir, screening for carriage of the HLA-B*5701 allele should be performed in any HIV-infected patient, irrespective of racial origin. Abacavir should not be used in patients known to carry the HLA-B*5701 allele.

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Mechanism of Action
Abacavir is a carbocyclic synthetic nucleoside analogue and an antiviral agent. Intracellularly, abacavir is converted by cellular enzymes to the active metabolite carbovir triphosphate, an analogue of deoxyguanosine-5'-triphosphate (dGTP). Carbovir triphosphate inhibits the activity of HIV-1 reverse transcriptase (RT) both by competing with the natural substrate dGTP and by its incorporation into viral DNA. Viral DNA growth is terminated because the incorporated nucleotide lacks a 3'-OH group, which is needed to form the 5′ to 3′ phosphodiester linkage essential for DNA chain elongation.

C14H18N6O

286.34

286.154

136470-78-5

Abacavir sulfate;188062-50-2;Abacavir monosulfate;216699-07-9;Abacavir hydrochloride;136777-48-5;Abacavir-d4;1260619-56-4;rel-Abacavir-d4;1217731-56-0

441300

White to off-white solid powder

1.7±0.1 g/cm3

636.0±65.0 °C at 760 mmHg

161 °C(dec.)

338.4±34.3 °C

0.0±2.0 mmHg at 25°C

1.864

0.72

3

6

4

21

414

2

C1CC1NC2=C3C(=NC(=N2)N)N(C=N3)[C@@H]4C[C@@H](C=C4)CO

MCGSCOLBFJQGHM-SCZZXKLOSA-N

InChI=1S/C14H18N6O/c15-14-18-12(17-9-2-3-9)11-13(19-14)20(7-16-11)10-4-1-8(5-10)6-21/h1,4,7-10,21H,2-3,5-6H2,(H3,15,17,18,19)/t8-,10+/m1/s1

[(1S,4R)-4-[2-amino-6-(cyclopropylamino)purin-9-yl]cyclopent-2-en-1-yl]methanol

EpzicomABC, Ziagen

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO : ~100 mg/mL (~349.25 mM)
H2O : ~2 mg/mL (~6.98 mM)

Solubility in Formulation 1: ≥ 2.5 mg/mL (8.73 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 2.5 mg/mL (8.73 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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Solubility in Formulation 3: ≥ 2.5 mg/mL (8.73 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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Solubility in Formulation 4: 3.33 mg/mL (11.63 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with heating and sonication.

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 (Please use freshly prepared in vivo formulations for optimal results.)