UC-781(UC-781) - 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

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

Chemtura Corp.

在研机构-

非在研机构

Contraception Research and DevelopmentAdamisConrad AG

+ [1]

最高研发阶段终止临床2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C17H18ClNO2S

InChIKeyYZHIXLCGPOTQNB-UHFFFAOYSA-N

CAS号178870-32-1

关联

4

项与 UC-781 相关的临床试验

NCT00446979 / Completed临床1期IIT

Phase I Study of the Safety and Acceptability of UC-781 Topical Vaginal Microbicide in Women and Acceptability in Their Male Partners,Chiang Rai, Thailand

This study will help determine whether UC-781 gel is safe when applied to the vagina twice daily for 14 days, and will assess whether women and men find the gel acceptable to use.

开始日期2007-06-01

申办/合作机构

Centers for Disease Control & Prevention

[+1]

NCT00408538 / Completed临床1期IIT

A Phase 1 Randomized, Blinded, Placebo-Controlled Safety and Acceptability Study of the UC-781 Vaginal Microbicide Gel Formulation Applied Rectally in HIV-1 Seronegative Adults

This study is the first to try this product in the rectum of humans. This study is only to find out if the gel is safe for use in the rectum, not to see if the gel works. Information gathered from this study will help investigators decide whether this gel is safe enough to move onto the next phase of studies.
Information gathered from this study will also help investigators determine what participants did and did not like about the product and what types of products people might want to use in the future. Currently condoms and abstinence are the only methods proven to prevent the spread of HIV sexually.

开始日期2006-12-01

申办/合作机构

University of California, Los Angeles

[+2]

NCT00441909 / Completed临床1期IIT

Phase I Study of the Safety and Persistence of 0.1% UC-781 Vaginal Gel in HIV-1 Seronegative Women

Vaginal microbicides are compounds that may protect women from HIV and other sexually transmitted infections (STIs). This study will determine the safety of the microbicide UC-781 by comparing the effects of keeping the microbicide in the vagina for different lengths of time.

开始日期2006-04-01

申办/合作机构

National Institute of Allergy & Infectious Diseases

[+1]

100 项与 UC-781 相关的临床结果

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100 项与 UC-781 相关的转化医学

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100 项与 UC-781 相关的专利（医药）

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99

项与 UC-781 相关的文献（医药）

2016-04-24·AIDS2区 · 医学

Maraviroc and reverse transcriptase inhibitors combinations as potential preexposure prophylaxis candidates

2区 · 医学

Article

作者: Alcami, Jose ; Shattock, Robin J. ; Armanasco, Naomi ; Garcia-Perez, Javier ; Ziprin, Paul ; Nuttall, Jeremy ; Olejniczak, Natalia ; Herrera, Carolina

OBJECTIVEReceptive anal intercourse in both men and women is associated with the highest probability for sexual acquisition of HIV infection. As part of a program to develop an effective prevention strategy, we performed an ex-vivo preclinical evaluation to determine the efficacy of multiple double combinations of maraviroc (MVC) and reverse transcriptase inhibitors (RTIs).DESIGNThe entry inhibitor, MVC, a nucleotide RTI, tenofovir and two non-nucleoside RTIs, UC781 and TMC120 (dapivirine, DPV), were used in double, combinations against a panel of CCR5-using clade B and clade C HIV-1 isolates and against MVC-escape variants. A gel-formulated version of MVC-DPV combination was also tested.METHODSIndicator cells, cocultures of immature dendritic cells with CD4T cells, and colorectal tissue explants were used to assess antiviral activity of drug combinations.RESULTSAll dual MVC-RTI combinations tested inhibited MVC-sensitive and resistant isolates in cellular and colorectal explants models. All the combinations were positive with no reduction in the activity of MVC. In tissue explants, the combinations against all viral isolates tested produced an increase in the activity of MVC. An initial gel-formulation of MVC-DPV combination showed greater and prolonged antiviral activity of MVC in mucosal tissue explants.CONCLUSIONThis study demonstrates that combinations based on antiretroviral drugs inhibiting HIV transmission at viral entry and reverse transcription have potential as prevention strategies against colorectal transmission of HIV-1 including MVC-resistant isolates. Preclinical evaluation with colorectal tissue explants indicates that a gel-formulation of MVC-DPV is an effective candidate colorectal microbicide.

2015-09-01·Contraception2区 · 医学

Assessing the potential of the Woman’s Condom for vaginal drug delivery

2区 · 医学

Article

作者: Dezzutti, Charlene S ; Kramzer, Lindsay F ; Friend, David ; Schubert, Jesse ; Rohan, Lisa C ; Moncla, Bernard J ; Cohen, Jessica

BACKGROUNDThe Woman's Condom is a new female condom that uses a dissolvable polyvinyl alcohol capsule to simplify vaginal insertion. This preclinical study assessed the feasibility to incorporate an antiviral drug, UC781, into the Woman's Condom capsule, offering a unique drug delivery platform.STUDY DESIGNUC781 capsules were fabricated using methods from the development of the Woman's Condom capsules as well as those used in vaginal film development. Capsules were characterized to evaluate physical/chemical attributes, Lactobacillus compatibility, in vitro safety and bioactivity, and condom compatibility.RESULTSTwo UC781 capsule platforms were assessed. Capsule masses (mg; mean±SD) for platforms 1 and 2 were 116.50±18.22 and 93.80±8.49, respectively. Thicknesses were 0.0034±0.0004 in and 0.0033±0.0004 in. Disintegration times were 11±3 s and 5±1 s. Puncture strengths were 21.72±3.30 N and 4.02±0.83 N. Water content measured 6.98±1.17% and 7.04±1.92%. UC781 content was 0.59±0.05 mg and 0.77±0.11 mg. Both platforms retained in vitro bioactivity and were nontoxic to TZM-bl cells and Lactobacillus. Short-term storage of UC781 capsules with the Woman's Condom pouch did not decrease condom mechanical integrity.CONCLUSIONSUC781 was loaded into a polymeric capsule similar to that of the Woman's Condom product. This study highlights the potential use of the Woman's Condom as a platform for vaginal delivery of drugs relevant to sexual/reproductive health, including those for short- or long-acting HIV prevention.IMPLICATIONSWe determined the proof-of-concept feasibility of incorporation of an HIV-preventative microbicide into the Woman's Condom capsule. This study highlights various in vitro physical and chemical evaluations as well as bioactivity and safety assessments necessary for vaginal product development related to female sexual and reproductive health.

2015-02-01·Drug Delivery and Translational Research3区 · 医学

Lack of in vitro–in vivo correlation for a UC781-releasing vaginal ring in macaques

3区 · 医学

Article

作者: Ron A. Otten ; R. Karl Malcolm ; Christopher McConville ; Priya Srinivasan ; Clare F. McCoy ; Angela Holder ; James M. Smith ; David R. Friend ; Gustavo F. Doncel ; Salvatore Butera ; James Mitchell

This study describes the preclinical development of a matrix-type silicone elastomer vaginal ring device designed to provide controlled release of UC781, a non-nucleoside reverse transcriptase inhibitor. Testing of both human- and macaque-sized rings in a sink condition in vitro release model demonstrated continuous UC781 release in quantities considered sufficient to maintain vaginal fluid concentrations at levels 82-860-fold higher than the in vitro IC50 (2.0 to 10.4 nM) and therefore potentially protect against mucosal transmission of HIV. The 100-mg UC781 rings were well tolerated in pig-tailed macaques, did not induce local inflammation as determined by cytokine analysis and maintained median concentrations in vaginal fluids of UC781 in the range of 0.27 to 5.18 mM during the course of the 28-day study. Analysis of residual UC781 content in rings after completion of both the in vitro release and macaque pharmacokinetic studies revealed that 57 and 5 mg of UC781 was released, respectively. The pharmacokinetic analysis of a 100-mg UC781 vaginal ring in pig-tailed macaques showed poor in vivo-in vitro correlation, attributed to the very poor solubility of UC781 in vaginal fluid and resulting in a dissolution-controlled drug release mechanism rather than the expected diffusion-controlled mechanism.

100 项与 UC-781 相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
-	-	-	DB05871

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2期	-	Adamis	-
HIV感染	临床2期	-	Adamis	-
HIV感染	临床2期	-	Chemtura Corp.	-
HIV感染	临床2期	-	Chemtura Corp.	-

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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


IAS2006	N/A	HIV感染	-	UC781	襯鬱廠觸鏇積範鹽糧製(衊糧糧醖願遞選壓繭夢) = 鹽網襯鏇遞積蓋簾鏇網襯製築憲淵廠鬱鹽鹽襯 (鹽衊構餘範憲選醖壓窪 )	-	2006-01-01
IAS2001	N/A	HIV感染	-	UC781	淵窪鏇醖夢膚鹹膚顧壓(襯齋鑰遞簾淵淵衊壓襯) = 窪壓鹽鹹積鬱獵齋餘構艱窪衊壓製窪構構膚鏇 (蓋繭獵鹹觸願構餘衊襯 )	-	2001-01-01