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
After oral administration, it is rapidly and extensively distributed (tablet bioavailability is 83%). Following twice-daily administration of 300 mg tablets, 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. Following administration of a 600 mg dose of SUP14C-abacavir, the elimination of abacavir was quantitatively analyzed by a mass balance study: 99% of the radioactive material was recovered, 1.2% was excreted in the urine as abacavir, 30% as a 5′-carboxylic acid metabolite, 36% as a 5′-glucuronide metabolite, and 15% as unidentified minor metabolites in the urine. Fecal excretion accounted for 16% of the total dose. Abacavir is excreted unchanged via the kidneys, with limited excretion pathways in the human body.
0.86 ± 0.15 L/kg [intravenous administration]
0.80 ± 0.24 L/hr/kg [single intravenous dose of 150 mg for asymptomatic HIV-1 infected adults]
Metabolism/Metabolites
Primarily metabolized in the liver by alcohol dehydrogenases and glucuronyl transferases to 5'-carboxylic acid metabolites and 5'-glucuronide metabolites. These metabolites do not possess antiviral activity. Abacavir is hardly metabolized by cytochrome P450 enzymes.
Biological half-life
1.54 ± 0.63 hours

Hepatotoxicity
Up to 6% of patients taking abacavir may experience serum transaminase levels exceeding 5 times the upper limit of normal. These elevations are usually mild and transient, requiring no dose adjustment. Clinically significant hepatotoxicity is rare, but isolated cases have been reported (usually without jaundice). Liver injury typically occurs against the backdrop of abacavir hypersensitivity syndrome and may be masked by allergic symptoms such as fever, rash, and fatigue. It usually appears within 1 to 3 months after starting abacavir. Serum enzyme profiles can be hepatocellular or cholestatic. Patients usually recover rapidly within 4 weeks after discontinuation of the drug. Probability score: C (likely the cause of clinically significant liver injury). Pregnancy and Lactation Effects ◉ Overview of Use During Lactation Abacavir is present in small amounts in breast milk. Information on the safety of using this drug during lactation is very limited. Achieving and maintaining viral suppression through antiretroviral therapy can reduce the risk of breast milk transmission to below 1%, but not zero. For HIV-infected individuals receiving antiretroviral therapy with persistently undetectable viral load, breastfeeding should be supported if chosen. If viral load is not suppressed, pasteurized donated breast milk or formula is recommended.
◉ Effects on Breastfed Infants
An HIV-positive mother took a once-daily combination tablet (Triumeq) containing 50 mg dolutegravir, 600 mg abacavir sulfate, and 300 mg lamivudine. Her infant was exclusively breastfed for approximately 30 weeks, followed by partial breastfeeding for approximately 20 weeks. No significant side effects were observed.
◉ Effects on Lactation and Breast Milk
Gynecomastia has been reported in men receiving highly active antiretroviral therapy. Gynecomastia is initially unilateral, but approximately half of cases develop into bilateral gynecomastia. No changes in serum prolactin levels were observed, and it usually resolves spontaneously within one year even with continued medication. Some case reports and in vitro studies suggest that protease inhibitors may cause hyperprolactinemia and galactorrhea in some male patients, but this conclusion remains controversial. The implications of these findings for lactating women are unclear. Prolactin levels in established lactating mothers may not affect their ability to breastfeed. Protein binding is moderate (approximately 50%). Abacavir's binding to plasma proteins is concentration-independent.

[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, chemically named (1S)-cyclopent-2-en-1-ylmethanol, where the pro-R hydrogen at the 4-position is replaced by a 2-amino-6-(cyclopropylamino)-9H-purine-9-yl group. It is a nucleoside reverse transcriptase inhibitor (NRTI) with anti-HIV activity and is often used in combination with other antiretroviral drugs for the treatment of HIV infection (especially in its sulfate form). It is an HIV-1 reverse transcriptase inhibitor, an antiviral drug, and also a drug allergen. Abacavir (trade name: Ziagen) is a prescription drug approved by the U.S. Food and Drug Administration (FDA) for the treatment of HIV infection in adults, children, and infants. Abacavir is often used in combination with other anti-HIV drugs. Abacavir (ABC) is a potent nucleoside analog reverse transcriptase inhibitor (NRTI) used to treat HIV infection and AIDS. Chemically, it is a synthetic carbocyclic nucleoside, an enantiomer with an absolute 1S,4R configuration on the cyclopentene ring. In vivo, abacavir sulfate dissociates into the free base abacavir. Abacavir is a human immunodeficiency virus nucleoside analog reverse transcriptase inhibitor. Its mechanism of action is as a nucleoside reverse transcriptase inhibitor and a cytochrome P450 1A1 inhibitor. Abacavir sulfate is a nucleoside analog and reverse transcriptase inhibitor used in combination with other drugs to treat human immunodeficiency virus (HIV) infection and acquired immunodeficiency syndrome (AIDS). Abacavir is a rare cause of clinically significant drug-induced liver injury. Abacavir is a nucleoside reverse transcriptase inhibitor, an analog of guanosine. This drug can reduce HIV viral load, delay or prevent damage to the immune system, and reduce the risk of developing AIDS.

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Drug Indications
Abacavir is used in combination with other antiretroviral drugs to treat HIV-1 infection.
It is used in combination with dolutegravir and lamivudine to treat HIV-1 infection in adults and children weighing ≥10 kg.
FDA Label
Ziagen is indicated for use as an antiretroviral combination therapy in adults, adolescents, and children for the treatment of human immunodeficiency virus (HIV) infection. The efficacy of Ziagen is primarily based on studies in treatment-naïve adult patients receiving combination therapy using a twice-daily dosing regimen. All HIV-infected individuals, regardless of race, should be screened for HLA-B5701 allele carriage before initiating abacavir treatment. Abacavir is contraindicated in patients known to carry the HLA-B5701 allele.

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Mechanism of Action
Abacavir is a carbocyclic synthetic nucleoside analog and an antiviral drug. Intracellularly, abacavir is converted by cellular enzymes to its active metabolite, carbovir triphosphate, an analog of deoxyguanosine-5'-triphosphate (dGTP). Carbovir triphosphate inhibits HIV-1 reverse transcriptase (RT) activity by competing with the natural substrate dGTP and by incorporating it into viral DNA. Viral DNA growth terminates because the incorporated nucleotide lacks a 3'-OH group, which is essential for the formation of a 5' to 3' phosphodiester bond, crucial 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.)