依克立达(Elacridar) - 药物靶点：ABCG2 x P-gp_在研适应症：肿瘤_专利_临床

概要

基本信息

药物类型

小分子化药

别名

Elacridar hydrochloride (USAN)

+ [6]

靶点

ABCG2 x P-gp

作用方式

抑制剂

作用机制

ABCG2抑制剂(ATP结合盒转运子亚家族G成员2抑制剂)、P-gp抑制剂(P-糖蛋白-1抑制剂)

治疗领域

肿瘤

在研适应症

肿瘤

非在研适应症-

原研机构

GSK Plc

在研机构

Chiba University

非在研机构

GSK Plc

权益机构-

最高研发阶段临床前

首次获批日期-

最高研发阶段(中国)-

特殊审评-

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结构/序列

分子式C34H33N3O5

InChIKeyOSFCMRGOZNQUSW-UHFFFAOYSA-N

CAS号143664-11-3

关联

2

项与依克立达相关的临床试验

NL-OMON38922

/ CompletedN/AIIT

Pharmacokinetic study of a new formulation of elacridar - Pharmacokinetic study of a new formulation of elacridar

开始日期2013-10-25

申办/合作机构-

EUCTR2010-020759-30-AT

/ Not yet recruitingN/AIIT

A pilot study to assess [11C]elacridar and [11C]tariquidar as two positron emission tomography radiotracers for visualization of P-glycoprotein in humans. - [11C]inhibitors

开始日期2010-11-03

申办/合作机构

Medizinische Universität Graz

100 项与依克立达相关的临床结果

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100 项与依克立达相关的转化医学

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100 项与依克立达相关的专利（医药）

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697

项与依克立达相关的文献（医药）

2025-05-01·Placenta

Analysis of drug transporter expression in syncytiotrophoblast derived from human placental stem cells: Expression and function of efflux transporters

Article

作者: Nishimura, Ayako ; Ueda, Ayami ; Furugen, Ayako ; Umazume, Takeshi ; Kobayashi, Masaki ; Narumi, Katsuya ; Sawada, Riko

OBJECTIVEThe placenta is a vital organ for exchanging nutrients, endogenous substances, and xenobiotics between mother and fetus. The syncytiotrophoblast (ST) is crucial in maintaining the placental barrier. Human trophoblast stem cells (hTSCs) have been recently established; however, their utility in studying placental transport functions has not been fully elucidated. This study investigated the expression and function of transporters in hTSC-derived ST cells.METHODSTS^CT cells, as hTSCs, were differentiated into ST-like cells (ST-TS^CT), and the gene expression of 84 transporters in ST-TS^CT cells was evaluated using a PCR array. BeWo cells, a widely used trophoblast model, were used for comparison. BeWo cells were differentiated into ST-like cells using forskolin [BeWo (FK)]. The protein levels of efflux transporters were examined by western blotting, and functional assays were performed using typical fluorescent substrates.RESULTSTransporter gene expression levels were higher in ST-TS^CT than in BeWo (FK) cells, with 27 genes showing more than a 3-fold increase. Ten of these genes were exclusively expressed in ST-TS^CT. Western blotting revealed the presence of efflux transporters, including P-glycoprotein (P-gp/ABCB1), breast cancer resistance protein (BCRP/ABCG2), and multidrug resistance-associated protein 2 (MRP2/ABCC2). Furthermore, the accumulation of typical substrates (Rhodamine123 for P-gp, Hoechst33342 and BODIPY™ FL Prazosin for BCRP, and 5(6)-carboxy-2',7'-dichlorofluorescein diacetate for MRP) significantly increased when transporter inhibitors (elacridar, Ko143, and MK571) were applied.CONCLUSIONThis study showed higher transporter expression in ST-TS^CT than that in a traditional trophoblast model. Furthermore, the functional expression of efflux transporters was observed. ST-TS^CT is valuable for investigating placental transport functions.

2025-05-01·Drug Metabolism and Disposition

In vitro assessment of ATP-binding cassette transporters and their functional genetic polymorphisms on fluoroquinolone accumulation in human embryonic kidney 293 recombinant cell lines

Article

作者: Elens, Laure ; Mahieu, Gwenaëlle ; Van Bambeke, Françoise ; Haufroid, Vincent

Fluoroquinolone tissue distribution and cellular accumulation are hindered by efflux transporters, including ATP-binding cassette subfamily B member 1 (ABCB1), ATP-binding cassette subfamily G member 2 (ABCG2), and ATP-binding cassette subfamily C member 4 (ABCC4). Genetic polymorphisms (single-nucleotide polymorphisms) can impact transporter activity, leading to interindividual variability in the systemic and cellular pharmacokinetics of their substrates. This study assesses the impact of these transporters on moxifloxacin and ciprofloxacin (CIP) cellular accumulation in vitro, and the effect of common single-nucleotide polymorphisms in ABCB1 [c.1199G>A (rs2229109); common haplotype c.1236C>T (rs1128503), c.2677G>T/A (rs2032582), and c.3435C>T (rs1045642)] and ABCG2 [c.421C>A (rs2231142)]. Recombinant human embryonic kidney (HEK) cell lines overexpressing wild-type or variant transporters were generated via stable plasmid transfection. The impact of transporter overexpression on fluoroquinolone cell disposition was assessed through accumulation experiments in the presence of specific inhibitors to establish the link between transporter expression and differential accumulation. Results indicated that ABCB1 overexpression reduced moxifloxacin cellular concentration by 30% but inconsistently with that of CIP and that zosuquidar or elacridar reversed these effects. ABCG2 had no impact. ABCC4 markedly reduced CIP accumulation by 25%, even at the basal level, an effect reversed by MK517. Contrarily to the wild-type and the c.1199A carriers, ABCB1 CGT and TTT variants did not reduce antibiotic accumulation. In conclusion, moxifloxacin and CIP are substrates of the wild-type and 1199G>A ABCB1, while CGT and TTT haplotypes had a marginal impact on fluoroquinolone transport by ABCB1. CIP is a preferential ABCC4 substrate. Because of the large body distribution of these transporters, our findings may help rationalize their role and the impact of their polymorphisms in fluoroquinolone disposition in tissues and cells. SIGNIFICANCE STATEMENT: This study demonstrates that moxifloxacin and ciprofloxacin are substrates of ABCB1, with ciprofloxacin also transported by ABCC4. Specific ABCB1 polymorphisms (CGT and TTT haplotypes) reduce the ABCB1 transport capacity toward fluoroquinolones. These findings highlight the importance of considering ABCB1 and ABCC4 inducers or inhibitors, which may affect fluoroquinolone disposition in tissues and cells, as well as ABCB1 polymorphisms that could explain interindividual variability in pharmacokinetic profiles.

2025-04-14·ChemMedChem

ABT, Elacridar and Bile‐Duct Cannulated Rats: Tools to Understand Pharmacokinetics

Review

作者: Ouvry, Gilles

AbstractOptimizing pharmacokinetics is an integral part of drug design, albeit a lesser understood one from the medicinal chemist's perspective. Over the years, molecular tools and experimental strategies have been developed to better understand the fate of compounds. Among these, the use of aminobenzotriazole (ABT), elacridar and bile‐duct cannulated rats have been instrumental in gaining valuable PK insights, with a direct impact on drug design.

100 项与依克立达相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D03968	-	-	DB04881

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
肿瘤	临床前	加拿大	-	-
肿瘤	临床前	-	GSK Plc	-
肿瘤	临床前	欧洲	-	-
肿瘤	临床前	美国	-	-

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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


P10.21.A (EANO2023)	N/A	脑癌	-	Elacridar	壓範鹽餘蓋餘膚餘醖夢(壓簾選積顧窪餘襯廠壓) = 壓壓選壓製齋築窪鹽憲醖積鹹觸選顧艱繭選醖 (艱齋憲鹹獵艱顧鏇壓齋 )	-	2023-09-08
EANM2016	N/A	P-glycoprotein	3	Elacridar	鹽齋憲窪淵艱餘衊鬱壓(繭鑰遞築壓積艱簾築繭) = 鑰憲糧夢網鑰範顧構襯艱願觸構襯鹹構範獵齋 (獵憲鬱憲遞顧糧獵餘製 )	积极	2016-09-21
EANM2016	N/A	P-glycoprotein	3	High-dose Erlotinib	鹽齋憲窪淵艱餘衊鬱壓(繭鑰遞築壓積艱簾築繭) = 艱鏇簾鹽艱繭繭廠選構艱願觸構襯鹹構範獵齋 (獵憲鬱憲遞顧糧獵餘製 )	积极	2016-09-21
SNMMI2016	N/A	-	-	High dose erlotinib	壓糧夢遞選遞遞觸願鹽(齋膚憲襯鬱範廠網艱鬱) = 築蓋鬱醖餘廠鹹鏇選鏇窪製顧艱憲餘衊選醖衊 (願鬱膚選餘齋壓鬱蓋夢, 0.03)	-	2016-05-24
SNMMI2016	N/A	-	-	Elacridar	壓糧夢遞選遞遞觸願鹽(齋膚憲襯鬱範廠網艱鬱) = 簾遞夢製網製鬱鏇製膚窪製顧艱憲餘衊選醖衊 (願鬱膚選餘齋壓鬱蓋夢, 0.35)	-	2016-05-24
ASCO2004	临床1期	晚期癌症	23	Topotecan 2 mg + Elacridar 100 mg	繭鑰膚觸夢繭壓餘繭構(範廠夢蓋醖積廠鑰鹽繭) = DLTs consisting of CTC Grade 4 leukocytopenia, neutropenia and thrombocytopenia were observed at 2.5 mg/d of topotecan. 願構廠淵網襯鹹淵獵淵 (製鏇廠窪網蓋範糧艱襯 ) 更多	-	2004-07-15