In prostate cancer cell lines, abacavir (15 and 150 μM, 0-120 h) monosulfate suppresses cell proliferation, modifies the expression of LINE-1 mRNA, influences the progression of the cell cycle, and promotes senescence[1]. Abacavir monosulfate (15 and 150 μM, 18 h) dramatically decreases cell migration and prevents cell invasion[1]. Fat apoptosis is induced by abacavir monsulfate[4].

Abacavir (0.7–7.5 μg/mL, 100 μL, intrascrotal injection; 100 and 200 mg/kg, po; 4 h) increased the formation of thrombus in a dose-dependent manner[2]. In high-risk mice carrying medulloblastoma, abacavir (50 mg/kg/d; ip; 14 days) monosulfate combined with 0.1 mg/kg/d Decitabine improves survival[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: demonstrated a dose-dependent growth inhibition on 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 very high accumulation of cells in S phase in PC3 and LNCaP cells, and G2/M phase increment 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 h
Experimental Results: Dramatically decreased cell migration. Cell Invasion Assay[1]
Cell Types: PC3 and LNCaP
Tested Concentrations: 15 and 150 μM
Incubation Duration: 18 h
Experimental Results: Dramatically inhibited cell invision.

Animal/Disease Models: Male mice (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 for 4 h
Experimental Results: Dose-dependently promoted thrombus formation.

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

Absorption, Distribution and Excretion
Following oral administration of 600 mg of radiolabeled abacavir, 82.2% of the dose was excreted in the urine and 16% in the feces. Of the radioactive material recovered in the urine, 30% was from the 5-carboxylic acid metabolite, 36% from the 5-glucuronide metabolite, and 1.2% from the unchanged abacavir; unidentified minor metabolites accounted for 15% of the radioactive material recovered in the urine. It is unclear whether abacavir is distributed into human milk; however, it is distributed into breast milk in rats. Abacavir crosses the rat placenta. Abacavir has high oral bioavailability, regardless of food intake. The cerebrospinal fluid to plasma AUC ratio is approximately 0.3. For more complete data on the absorption, distribution, and excretion of abacavir sulfate (7 metabolites), please visit the HSDB record page.

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Metabolism/Metabolites
Abacavir is partially metabolized by alcohol dehydrogenase (to produce 5'-carboxylic acid) and glucuronidation (to produce 5'-glucuronide).
The metabolic pathway of abacavir is not fully understood, but the drug is metabolized in the liver. Abacavir is metabolized by alcohol dehydrogenase to produce 5'-carboxylic acid, and by glucuronidase to produce 5'-glucuronide; these metabolites do not appear to have any antiviral activity. Cytochrome P450 isoenzymes are involved in abacavir metabolism to a limited extent.
Intracellularly, abacavir is phosphorylated by adenosine phosphotransferase to abacavir monophosphate; abacavir monophosphate is then converted to carbovir monophosphate by cytoplasmic enzymes, and then to carbovir triphosphate by cellular kinases. The intracellular (host cell) conversion of abacavir to carbovir triphosphate is necessary for the drug to exert its antiviral activity. In vitro experiments showed that the intracellular half-life of carbovir triphosphate (SRP: a metabolite of abacavir sulfate) in CD4+ CEM cells was 3.3 hours.
Biological half-life
In vitro experiments showed that the intracellular half-life of carbovir triphosphate (SRP: a metabolite of abacavir sulfate) in CD4+ CEM cells was 3.3 hours.
The plasma elimination half-life after a single oral dose of abacavir (administered as abacavir sulfate) was approximately 1.5 hours. In HIV-infected children aged 3 months to 13 years, the steady-state plasma elimination half-life after receiving 8 mg/kg abacavir every 12 hours (administered as an oral solution containing abacavir sulfate) was on average 1.3 hours, essentially the same as the half-life after a single dose. In patients with renal failure (glomerular filtration rate less than 10 mL/min) undergoing peritoneal dialysis, the plasma elimination half-life of the drug after a single oral dose of 300 mg abacavir was 1.33 hours.

Effects During Pregnancy and Lactation
◉ Overview of Lactation Use
Abacavir is present in small amounts in breast milk. Information on the safety of abacavir 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 a persistently low viral load, breastfeeding should be encouraged if chosen. If viral load is not suppressed, pasteurized donor 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 initially occurs unilaterally, but about half of the cases progress to bilateral gynecomastia. No changes in serum prolactin levels have been observed, and it usually resolves spontaneously within a year even with continued treatment. 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.

[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 (brand 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 must be used in combination with other HIV medications.
See also: Abacavir sulfate (note moved here).

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Drug Indications
Ziagen is indicated for the treatment of human immunodeficiency virus (HIV) infection in adults, adolescents, and children as part of an antiretroviral combination therapy. The efficacy of Ziagen is primarily based on studies in treatment-naïve adult patients using a twice-daily combination therapy regimen. All individuals living with HIV, regardless of race, should be screened for HLA-B5701 allele carrier status before initiating abacavir treatment. Abacavir is contraindicated in patients known to carry the HLA-B5701 allele.

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Mechanism of Action
Similar to dideoxynucleoside reverse transcriptase inhibitors (e.g., didanosin, lamivudine, stavudine, zalcitabine, zidovudine), the antiviral activity of abacavir appears to depend on the intracellular conversion of the drug to a 5-triphosphate metabolite; therefore, carbovir triphosphate (cyclic guanosine triphosphate) rather than unmetabolized abacavir appears to be the pharmacologically active form of the drug. The phosphorylation rates and enzymatic pathways involved in response to various nucleoside antiviral drugs vary significantly in human cells.
The enzymatic conversion of abacavir to carbovir triphosphate appears to be complex, involving certain steps and enzymes that differ from those of dideoxynucleoside reverse transcriptase inhibitors. Abacavir is phosphorylated by adenosine phosphotransferase to abacavir monophosphate, which is then converted to carbovir monophosphate by cytosolic enzymes. Subsequently, carbovir monophosphate is phosphorylated by cellular kinases to carbovir triphosphate. Abacavir is not a substrate of enzymes known to phosphorylate other nucleoside analogues (such as thymidine kinase, deoxycytidine kinase, adenosine kinase, and mitochondrial deoxyguanosine kinase). Because abacavir phosphorylation depends on cellular enzymes rather than viral enzymes, the drug can be converted to its active triphosphate derivative in both virus-infected and uninfected cells. Carbovir triphosphate is a structural analogue of deoxyguanosine-5-triphosphate (dGTP), a common substrate for viral RNA-directed DNA polymerases. Although the drug's antiretroviral activity may involve other mechanisms, carbovir triphosphate appears to compete with deoxyguanosine-5-triphosphate for viral RNA-directed DNA polymerase and is incorporated into viral DNA. Once incorporated into the viral DNA strand, carbovir triphosphate, rather than deoxyguanosine-5-triphosphate, prevents further 5',3' phosphodiester bond formation due to the lack of a 3-hydroxyl group, leading to premature termination of DNA synthesis. The complete mechanism of abacavir's antiviral activity is not fully elucidated. After being converted into a pharmacologically active metabolite, abacavir apparently inhibits the replication of retroviruses (including HIV-1 and HIV-2) by interfering with viral RNA-directed DNA polymerase (reverse transcriptase). Therefore, this drug exerts its antiretroviral effect as a reverse transcriptase inhibitor.

C14H20N6O5S

384.410800933838

384.121

216699-07-9

Abacavir;136470-78-5;Abacavir sulfate;188062-50-2;Abacavir hydrochloride;136777-48-5

9843042

White to off-white solid

5

10

4

26

496

2

S(O)(O)(=O)=O.N(C1CC1)C1N=C(N)N=C2N([C@H]3C=C[C@@H](CO)C3)C=NC=12

MBFKCGGQTYQTLR-SCYNACPDSA-N

InChI=1S/C14H18N6O.H2O4S/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;1-5(2,3)4/h1,4,7-10,21H,2-3,5-6H2,(H3,15,17,18,19);(H2,1,2,3,4)/t8-,10+;/m1./s1

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

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)

May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.

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Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)
*Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution.
Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)
Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil)
Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals).

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Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)]
*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.
Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline)
Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline)
Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline
Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil)
Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)

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Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium)
Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose
Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals).

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Oral Formulation 3: Dissolved in PEG400
Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose
Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose
Oral Formulation 6: Mixing with food powders

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Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.

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