Apricitabine
(Synonyms: 阿立他滨,SPD754; AVX754) 目录号 : GC49776
A nucleoside reverse transcriptase inhibitor
Cas No.:160707-69-7
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >95.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Apricitabine is a nucleoside reverse transcriptase inhibitor (NRTI) and derivative of 2’-deoxycytidine .1 It is phosphorylated intracellularly to its active form, apricitabine-5’-triphosphate, which competes with a monophosphate form for binding to HIV-1 reverse transcriptase and incorporation into the nascent viral DNA, inducing chain termination and HIV-1 replication. Apricitabine reduces HIV-1 infectivity in MT-4 and U937 cells (IC50s = 2.8 and 0.4 µM, respectively), as well as in isolated human cord blood mononuclear cells (CBMCs; IC50 = 0.4 µM).2
1.Cox, S., and Southby, J.Apricitabine--a novel nucleoside reverse transcriptase inhibitor for the treatment of HIV infection that is refractory to existing drugsExpert Opin. Investig. Drugs18(2)199-209(2009) 2.Mansour, T.S., Jin, H., Wang, W., et al.Structure-activity relationships among a new class of antiviral heterosubstituted 2′,3′-dideoxynucleoside analoguesNucleos. Nucleot.14(3-5)627-635(1995)
| Cas No. | 160707-69-7 | SDF | Download SDF |
| 别名 | 阿立他滨,SPD754; AVX754 | ||
| Canonical SMILES | O=C1N(C=CC(N)=N1)[C@]2([H])S[C@H](CO)OC2 | ||
| 分子式 | C8H11N3O3S | 分子量 | 229.3 |
| 溶解度 | DMSO: soluble | 储存条件 | -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 4.3611 mL | 21.8055 mL | 43.611 mL |
| 5 mM | 0.8722 mL | 4.3611 mL | 8.7222 mL |
| 10 mM | 0.4361 mL | 2.1805 mL | 4.3611 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Apricitabine: a nucleoside reverse transcriptase inhibitor for HIV infection
Ann Pharmacother 2009 Oct;43(10):1676-83.PMID:19737995DOI:10.1345/aph.1M160.
Objective: To review the pharmacology, pharmacokinetics, efficacy, and safety of Apricitabine, a nucleoside reverse transcriptase inhibitor that is currently under investigation and has fast-track approval status with the Food and Drug Administration. Data sources: A literature search was conducted using PubMed (1966-June 2009) to retrieve relevant material using the search terms Apricitabine, SPD754, and AVX754. References from selected articles were evaluated to identify other pertinent trials. Information was also obtained from the manufacturer. Study selection and data extraction: All English-language in vitro and in vivo studies and abstracts evaluating Apricitabine were reviewed and considered for inclusion. Preference was given to human data. Data synthesis: Apricitabine is a prodrug that is phosphorylated to its active triphosphate form intracellularly, which ultimately results in chain termination and inhibition of reverse transcription. Apricitabine is administered orally, displays linear pharmacokinetics, and is renally excreted with minimal to no hepatic metabolism. It has demonstrated antiretroviral activity against drug-resistant strains both in vitro and in vivo. In clinical studies, in both antiretroviral-naïve and treatment-experienced patients, Apricitabine achieved the primary endpoint of significant reductions in plasma viral load versus comparator. Further Phase 2 and 3 studies are currently enrolling. Safety analysis indicates that Apricitabine is well tolerated and has a low potential for causing mitochondrial damage. The most common adverse events reported include headache and rhinitis. Development of resistance or further gene mutations has not been shown in clinical studies to date. Conclusions: Although the role of Apricitabine in the treatment of HIV-1 infection has yet to be established, its activity against resistant HIV-1 strains and its tolerability profile will likely make it a viable second-line treatment option in patients who have failed regimens containing lamivudine or emtricitabine.
Apricitabine: a novel deoxycytidine analogue nucleoside reverse transcriptase inhibitor for the treatment of nucleoside-resistant HIV infection
Antivir Chem Chemother 2007;18(2):61-70.PMID:17542150DOI:10.1177/095632020701800201.
Existing nucleoside reverse transcriptase inhibitors for HIV disease are limited by problems of resistance and, in some cases, long-term toxicity. Apricitabine (ATC; formerly BCH10618, SPD754 and AVX754) is a deoxycytidine analogue nucleoside reverse transcriptase inhibitor in clinical development. ATC retains substantial in vitro activity against HIV-1 containing many mutations associated with nucleoside reverse transcriptase inhibitor resistance, showing a less than twofold reduction in susceptibility in the presence of either up to five thymidine analogue mutations or the M184V mutation. ATC showed a low potential for cellular or mitochondrial toxicity in vitro. ATC is well absorbed orally, with a bioavailability of 65-80%. Its plasma elimination half-life (approximately 3 h), and the intracellular half-life of its triphosphate (TP) metabolite (6-7 h) support twice-daily dosing. Intracellular ATC-TP levels are markedly reduced in the presence of lamivudine or emtricitabine, indicating that clinical co-administration of ATC together with these agents will not be possible. The drug is renally eliminated, giving a low potential for hepatic drug interactions. In a double-blind, randomized, placebo-controlled Phase II monotherapy trial in antiretroviral-naive patients, ATC doses of 1,200 and 1,600 mg/day reduced plasma viral load levels by 1.65 and 1.58 log10 HIV RNA copies/ml, respectively, after 10 days of treatment (P<0.0001 versus placebo). ATC showed a low propensity to select for resistance mutants in vitro and during clinical monotherapy. ATC was well tolerated in volunteers and in HIV-infected patients. This promising profile suggests that ATC may be useful in treating patients who have failed previous lamivudine- or emtricitabine-containing regimens. Further studies to evaluate the long-term efficacy and tolerability of ATC are underway.
Resistance profile of the new nucleoside reverse transcriptase inhibitor Apricitabine
J Antimicrob Chemother 2010 Feb;65(2):213-7.PMID:20007333DOI:10.1093/jac/dkp422.
Apricitabine is a novel deoxycytidine nucleoside reverse transcriptase inhibitor (NRTI) currently in clinical development for the treatment of HIV infection. Apricitabine shows antiviral activity in vitro against HIV-1 strains and clinical isolates with mutations in the reverse transcriptase that confer resistance to other NRTIs, including M184V, thymidine analogue mutations (TAMs), nucleoside-associated mutations such as L74V and certain mutations at codon 69. Apricitabine has shown activity in treatment-experienced HIV-1-infected patients with NRTI resistance (with M184V and up to five TAMs) as well as in treatment-naive patients. Resistance to Apricitabine is slow to develop in vitro and there has been little evidence of development of resistance to Apricitabine in clinical use thus far, including patients receiving Apricitabine for up to 48 weeks. The resistance profile of Apricitabine suggests there is a low potential for cross-resistance with the currently available NRTIs and, thus, Apricitabine may provide a treatment option for treatment-experienced HIV-1-infected patients with resistance to other NRTIs. In particular, the activity of Apricitabine in the presence of the M184V mutation, which confers high-level resistance to lamivudine and emtricitabine, lends it to being used as a replacement for deoxycytidine analogues in patients who have failed treatment with lamivudine or emtricitabine.
Apricitabine--a novel nucleoside reverse transcriptase inhibitor for the treatment of HIV infection that is refractory to existing drugs
Expert Opin Investig Drugs 2009 Feb;18(2):199-209.PMID:19236266DOI:10.1517/13543780802641337.
Background: Apricitabine (ATC) is a nucleoside reverse transcriptase inhibitor (NRTI) being developed for the treatment of HIV. ATC has promising antiviral activity, including against HIV-1 containing reverse transcriptase mutations that confer resistance to other NRTIs. Objectives: This paper describes the development of ATC, including its in vitro activity, pharmacokinetics and clinical efficacy and safety. Methods: The current literature on ATC was reviewed. Results/conclusions: ATC is a novel deoxycytidine NRTI with good antiviral activity, both in vitro and in treatment-naïve and treatment-experienced HIV-1-infected patients, including those with resistance to other NRTIs. This activity is accompanied by a favourable safety profile and a low propensity to select for resistance. ATC may have a place in the treatment of patients who have failed previous treatment regimens due to the development of NRTI resistance as a replacement for existing drugs.
In vitro interactions between Apricitabine and other deoxycytidine analogues
Antimicrob Agents Chemother 2007 Aug;51(8):2948-53.PMID:17517847DOI:10.1128/AAC.01204-06.
Apricitabine is a novel deoxycytidine analogue reverse transcriptase inhibitor that is under development for the treatment of human immunodeficiency virus type 1 (HIV-1) infection. Apricitabine is phosphorylated to its active triphosphate by deoxycytidine kinase, which is also responsible for the intracellular phosphorylation of lamivudine (3TC) and emtricitabine (FTC); hence, in vitro studies were performed to investigate possible interactions between Apricitabine and these agents. Human peripheral blood mononuclear cells (PBMC) were incubated for 24 h with various concentrations of (3)H-labeled or unlabeled Apricitabine, 3TC, or FTC. Intracellular concentrations of parent compounds and their phosphorylated derivatives were measured by high-performance liquid chromatography. In other experiments, viral reverse transcriptase activity was measured in PBMC infected with HIV-1 bearing M184V in the presence of various concentrations of Apricitabine and 3TC. [(3)H]Apricitabine and [(3)H]3TC were metabolized intracellularly to form mono-, di-, and triphosphates. 3TC and FTC (1 to 10 microM) produced concentration-dependent decreases in Apricitabine phosphorylation; in contrast, Apricitabine at concentrations of up to 30 muM had no effect on the phosphorylation of 3TC or FTC. The combination of Apricitabine and 3TC reduced the antiviral activity of Apricitabine against HIV-1: Apricitabine concentrations producing 50% inhibition of viral reverse transcriptase were increased two- to fivefold in the presence of 3TC. These findings suggest that nucleoside reverse transcriptase inhibitors with similar modes of action may show biochemical interactions that affect their antiviral efficacy. It is therefore essential that potential interactions between combinations of new and existing agents be thoroughly investigated before such combinations are introduced into clinical practice.