阿立他滨(Apricitabine) - 药物靶点：RT_专利_临床

概要

基本信息

药物类型

小分子化药

别名

(-)dOTC、ATC

+ [4]

靶点

RT

作用机制

RT抑制剂(逆转录酶抑制剂)

治疗领域

免疫系统疾病感染泌尿生殖系统疾病

在研适应症-

非在研适应症

HIV感染

原研机构

Shire Pharmaceuticals Services Ltd.

在研机构-

非在研机构

Avexa LLC

最高研发阶段终止临床3期

首次获批日期-

最高研发阶段(中国)-

特殊审评-

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结构

分子式C8H11N3O3S

InChIKeyRYMCFYKJDVMSIR-RNFRBKRXSA-N

CAS号160707-69-7

关联

8

项与阿立他滨相关的临床试验

NCT00686270 / Withdrawn临床3期

A Phase 3, Open Label 96-week Extension Study of the Safety of Apricitabine in Treatment-experienced HIV-1 Infected Patients Who Have Completed Protocol AVX-301 or AVX-302 or Who Have Met the Criteria for Open-label Access to ATC Because of Virological Failure/Lack of Response

This study will examine the long term safety of apricitabine in HIV-1 infected patients from studies AVX-301 or AVX-302. Eligible patients are those who have either (a)completed studies AVX-301 or AVX-302; or (b)met the criteria for virological failure/lack of response, and consequently wish to withdraw early from studies AVX-301 or AVX-302.

开始日期2008-05-01

申办/合作机构

Avexa LLC

NCT00612898 / Terminated临床2/3期

A Phase 2b/3, Randomized, Double Blind, Dose Confirming Study of the Safety, Efficacy and Tolerability of Apricitabine Versus Lamivudine in Treatment-experienced HIV-1 Infected Patients With the M184V/I Mutation in Reverse Transcriptase

Apricitabine is a new NRTI which is active against drug-resistant HIV. NRTIs are often included as part of patients' treatment, but many HIV-infected patients develop resistance to commonly used NRTIs such as lamivudine (3TC) and emtricitabine (FTC). This study will examine whether including apricitabine as part of patients' treatment is more effective than including lamivudine,when patients change treatment because of drug resistance.

开始日期2008-02-01

申办/合作机构

Avexa LLC

ACTRN12606000443594 / Completed临床2期

An open label extension study to evaluate the long term safety and efficacy of apricitabine in controlling Human Immunodeficiency Virus (HIV) viral load and disease progression in treatment-experienced HIV-1 infected subjects

开始日期2006-09-01

申办/合作机构-

100 项与阿立他滨相关的临床结果

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100 项与阿立他滨相关的转化医学

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100 项与阿立他滨相关的专利（医药）

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270

项与阿立他滨相关的文献（医药）

2024-08-09·Antioxidants (Basel, Switzerland)

Effects of Acremonium terricola Culture on Lactation Performance, Immune Function, Antioxidant Capacity, and Intestinal Flora of Sows.

Article

作者: Chen, Qiangqiang ; Sun, Qian ; Hua, Weidong ; Xiao, Lixia ; Chen, Zhirong ; Zhang, Jinzhi

This study aimed to determine the effects of different doses of Acremonium terricola culture (ATC) on lactation performance, immune function, antioxidant capacity, and intestinal flora of sows. Forty-five Landrace sows (3-6 parity) were randomly assigned to the following three treatments from 85 days of gestation to 21 days after farrowing: a control diet (CON, basal diet), a low-dose Acremonium terricola culture diet (0.2% ATC, basal diet + 0.2% ATC), and a high-dose Acremonium terricola culture diet (0.4% ATC, basal diet + 0.4% ATC). Compared with the CON group, the supplementation of 0.2% ATC increased the average daily milk yield of sows by 4.98%, increased milk fat, total solids, and freezing point depression on day 1 postpartum (p < 0.05), increased serum concentration of Triiodothyronine, Thyroxin, and Estradiol on day 21 postpartum (p < 0.05). Compared with the CON group, the supplementation of 0.4% ATC increased the average daily milk yield of sows by 9.38% (p < 0.05). Furthermore, the supplementation of 0.2% ATC increased serum concentration of IgG, IgM, and IFN-γ, CD4 on day 1 postpartum (p < 0.05) and increased serum concentration of immunoglobulin A ( IgA), immunoglobulin G (IgG), immunoglobulin M ( IgM), complement 3 (C3), cluster of differentiation 4 (CD4), cluster of differentiation 8 (CD8), interferon-γ (IFN-γ) on day 21 postpartum (p < 0.05), while the supplementation of 0.4% ATC reduced serum concentration of IL-2 on day 21 postpartum (p < 0.05). Moreover, the supplementation of 0.4% ATC significantly increased serum concentration of catalase (CAT) (p < 0.05). Additionally, the supplementation of ATC affected the relative abundance of the intestinal flora at different taxonomic levels in sows and increased the abundance of beneficial bacteria such as in the norank_f__Eubacterium_coprostanoligenes group, Eubacterium_coprostanoligenes group, and Lachnospiraceae_XPB1014 group of sows, while reducing the abundance of harmful bacteria such as Phascolarctobacterium and Clostridium_sensu_stricto_1. These data revealed that the supplementation of ATC during late gestation and lactation can improve lactation performance, immune function, antioxidant capacity, and the gut microbiota. Compared with supplementation of 0.4% ATC, 0.2% ATC enhances the levels of thyroid-related hormones, specific antibodies, and cytokines in serum, promotes the diversity of beneficial gut microbiota, beneficial bacteria in the intestine, reduces the population of harmful bacteria, and thereby bolsters the immunity of sows. Hence, 0.2% ATC is deemed a more optimal concentration.

2024-08-01·Cancer Research

The DNA Methyltransferase Inhibitor 5-Aza-4′-thio-2′-Deoxycytidine Induces C>G Transversions and Acute Lymphoid Leukemia Development

Article

作者: Aplan, Peter D. ; Bertoli, Ryan M. ; Meltzer, Paul S. ; Klimaszewski, Haley ; Walter, Matthew J. ; Zhu, Yuelin J. ; Marasco, Madison R.B. ; Wokasch, Anthony ; Khanna, Ajay ; Gammell, Susannah ; Doroshow, James H. ; Cao, Dengchao ; Difilippantonio, Michael J. ; Chung, Yang Jo ; Walker, Robert L.

AbstractDNA methyltransferase inhibitors (DNMTi), most commonly cytidine analogs, are compounds that decrease 5′-cytosine methylation. DNMTi are used clinically based on the hypothesis that cytosine demethylation will lead to re-expression of tumor suppressor genes. 5-Aza-4′-thio-2′-deoxycytidine (Aza-TdCyd or ATC) is a recently described thiol-substituted DNMTi that has been shown to have anti-tumor activity in solid tumor models. In this study, we investigated the therapeutic potential of ATC in a murine transplantation model of myelodysplastic syndrome. ATC treatment led to the transformation of transplanted wild-type bone marrow nucleated cells into lymphoid leukemia, and healthy mice treated with ATC also developed lymphoid leukemia. Whole-exome sequencing revealed 1,000 acquired mutations, almost all of which were C>G transversions in a specific 5′-NCG-3′ context. These mutations involved dozens of genes involved in human lymphoid leukemia, such as Notch1, Pten, Pax5, Trp53, and Nf1. Human cells treated in vitro with ATC showed 1,000 acquired C>G transversions in a similar context. Deletion of Dck, the rate-limiting enzyme for the cytidine salvage pathway, eliminated C>G transversions. Taken together, these findings demonstrate a highly penetrant mutagenic and leukemogenic phenotype associated with ATC.Significance: Treatment with a DNA methyltransferase inhibitor generates a distinct mutation signature and triggers leukemic transformation, which has important implications for the research and clinical applications of these inhibitors.

2024-07-01·Reviews in Medical Virology

Efficacy and safety of adoptive T‐cell therapy in treating cytomegalovirus infections post‐haematopoietic stem cell transplantation: A systematic review and meta‐analysis

Review

作者: Ahmadvand, Mohammad ; Taherian, Mohammad Reza ; Daneshvar, Alireza ; Toufani, Shahin ; Barkhordar, Maryam ; Aliabadi, Leyla Sharifi ; Yaghmaie, Marjan ; Vaezi, Mohammad ; Bahri, Tanaz ; Azarbar, Pouya

AbstractCytomegalovirus (CMV) infection poses significant risks in allogeneic haematopoietic stem cell transplant (allo‐HSCT) recipients. Despite advances in antiviral therapies, issues such as drug resistance, side effects, and inadequate immune reconstitution remain. This systematic review and meta‐analysis aim to evaluate the efficacy and safety of adoptive cell therapy (ATC) in managing CMV infections in allo‐HSCT recipients. Adhering to preferred reporting items for systematic reviews and meta‐analyses guidelines, we conducted a comprehensive database search through July 2023. A systematic review and meta‐analysis were conducted on studies involving HSCT patients with CMV infections treated with ATC. The primary outcome was the response rate to ATC, and secondary outcomes included adverse events associated with ATC. The Freeman–Tukey transformation was applied for analysis. In the meta‐analysis of 40 studies involving 953 participants, ATC achieved an overall integrated response rate of 90.16%, with a complete response of 82.59% and a partial response of 22.95%. ATC source, HLA matching, steroid intake, and age group markedly influenced response rates. Donor‐derived T‐cell treatments exhibited a higher response rate (93.66%) compared to third‐party sources (88.94%). HLA‐matched patients demonstrated a response rate of 92.90%, while mismatched patients had a lower rate. Children showed a response rate of 83.40%, while adults had a notably higher rate of 98.46%. Adverse events were minimal, with graft‐versus‐host disease occurring in 24.32% of patients. ATC shows promising response rates in treating CMV infections post‐HSCT, with an acceptable safety profile. However, to establish its efficacy conclusively and compare it with other antiviral treatments, randomised controlled trials are essential. Further research should prioritise such trials over observational and one‐arm studies to provide robust evidence for clinical decision‐making.

1

项与阿立他滨相关的新闻（医药）

2009-06-04

·BioSpace

Positive Outcome Reached at 16 Weeks for Avexa Limited's ATC Phase III Trial

MELBOURNE, Australia--(BUSINESS WIRE)--Avexa Limited (ASX:AVX) announced that the Data Safety Monitoring Board (DSMB) met today to review the 16 week data from Avexa’s apricitabine (ATC) Phase III clinical trial. The DSMB reviewed the data and recommended continuation of the study with the 800mg dose. Patients taking the 1200mg dose will be transitioned to the optimum 800mg dose to continue their therapy.

100 项与阿立他滨相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
-	阿立他滨	J05AB	DB12855

研发状态

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
HIV感染	临床3期	意大利	Avexa LLC	2008-02-01
HIV感染	临床3期	澳大利亚	Avexa LLC	2008-02-01
HIV感染	临床3期	以色列	Avexa LLC	2008-02-01
HIV感染	临床3期	德国	Avexa LLC	2008-02-01
HIV感染	临床3期	美国	Avexa LLC	2008-02-01
HIV感染	临床3期	加拿大	Avexa LLC	2008-02-01
HIV感染	临床3期	英国	Avexa LLC	2008-02-01

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临床结果

适应症

分期

评价

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


IAS2008	N/A	HIV感染	51	Apricitabine 600mg	(鹹選鬱膚壓廠遞艱淵窪) = 築窪蓋壓膚簾襯餘遞艱蓋網廠膚簾簾鏇選範範 (選鹹選鑰憲鏇夢壓窪選 ) 更多	-	2008-01-01
				Apricitabine 800mg	(鹹選鬱膚壓廠遞艱淵窪) = 網鑰廠願觸簾願網鹽襯蓋網廠膚簾簾鏇選範範 (選鹹選鑰憲鏇夢壓窪選 ) 更多
IAS2006	N/A	HIV感染	-	apricitabine (HIV- subjects)	觸窪鬱構憲蓋製願構憲(膚壓襯夢鏇遞繭鏇構範) = 獵獵廠憲獵積製蓋廠窪窪鑰願壓網襯構餘衊夢 (網築糧憲齋糧繭鹽鹽範 ) 更多	-	2006-01-01
				apricitabine (HIV+ subjects)	觸窪鬱構憲蓋製願構憲(膚壓襯夢鏇遞繭鏇構範) = 窪糧鏇廠膚鏇淵構糧衊窪鑰願壓網襯構餘衊夢 (網築糧憲齋糧繭鹽鹽範 ) 更多
IAS2003	N/A	HIV感染	63	SPD754 400mg	醖網獵艱餘壓鹽鹹淵獵(簾獵觸鹹夢憲齋夢築觸) = 夢範鑰顧顧糧鹹製糧鹽製壓壓願淵窪夢鏇襯製 (築廠襯鹽鬱製艱夢繭構 )	积极	2003-01-01
				SPD754 800mg	醖網獵艱餘壓鹽鹹淵獵(簾獵觸鹹夢憲齋夢築觸) = 簾醖膚願壓鏇廠餘膚憲製壓壓願淵窪夢鏇襯製 (築廠襯鹽鬱製艱夢繭構 )
BCH-10618 (IAS2001)	N/A	-	-	BCH-10618	繭範獵觸選鑰選糧廠窪(鏇襯顧壓醖獵構築獵廠) = 獵壓醖廠淵鹽鏇鑰鏇齋遞積壓壓遞鑰襯蓋窪鹹 (築窪廠夢糧遞鏇繭製襯 ) 更多	-	2001-01-01