JI-101(JI-101) - 药物靶点：EphB4 x PDGFRβ x VEGFR2_专利_临床

概要

基本信息

药物类型

小分子化药

别名

靶点

EphB4 x PDGFRβ x VEGFR2

作用方式

拮抗剂、抑制剂

作用机制

EphB4拮抗剂(B型肝配蛋白受体-4拮抗剂)、PDGFRβ抑制剂(血小板衍生生长因子受体β抑制剂)、VEGFR2拮抗剂(血管内皮细胞生长因子受体2拮抗剂)

治疗领域

肿瘤消化系统疾病内分泌与代谢疾病+ [1]

在研适应症-

非在研适应症

晚期恶性实体瘤结肠癌肿瘤+ [3]

原研机构

Gilead Sciences, Inc.

在研机构-

非在研机构

Jubilant Innovation Pte Ltd.

University of Utah

Huntsman Cancer Institute

+ [2]

权益机构-

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-

登录后查看时间轴

关联

2

项与 JI-101 相关的临床试验

NCT01149434

/ Terminated临床1/2期IIT

Drug- Drug Interaction Study of JI-101 & Everolimus in Advanced Solid Tumors, Expansion Pharmacodynamic Study of JI-101 in Advanced Low Grade Endocrine Tumors, Ovarian Cancers or K-RAS Mutant Colon Cancers

The study consists of two parts: Drug Interaction (Pharmacokinetic) Phase and Pharmacodynamic Phase
The primary study objective for the Drug Interaction Study is to determine the pharmacokinetic interactions between RAD001 and JI-101.
The primary study objective for the Pharmacodynamic Study is progression-free survival at 2 moths, evaluated separately in each of the three cohorts.
These will include a determination of tumor response using Response Evaluation Criteria in Solid Tumors (RECIST) Criteria and an assessment of ephrinB4 expression in blood samples.
Secondary objectives are to determine safety and tolerability of JI-101. The investigational products are everolimus (42-O-(2-hydroxyethyl) rapamycin) and JI-101 (1-[1-(2-amino-pyridin-4-ylmethyl)-1H-indol-4-yl]-3-(5-bromo-2 methoxy-phenyl)-urea)
Eligible patients meeting all study entry criteria will be enrolled in the study. For the Drug Interaction study, patients with solid tumors will receive a single dose (10 mg) of Everolimus by mouth on Day 1 and Day 8 and JI-101 capsules (200 mg) by mouth on Day 8 and Day 15. For the Pharmacodynamic Study, all patients will receive JI-101 capsules by mouth (200 mg BID) for 28 day treatment cycles.

开始日期2010-09-01

申办/合作机构

University of Utah

[+1]

NCT00842335

/ Completed临床1/2期

A Multicenter, Phase 1/2, Open-Label, Dose-Escalation Study of JI-101, an Oral Angiogenesis Inhibitor, in Patients With Advanced Solid Tumors

The purpose of this study, the first clinical trial of JI-101, is to determine the maximum tolerated dose of JI-101 when given orally to patients with solid tumors. Safety, tolerability, pharmacokinetics, pharmacodynamics, and the effects of the drug on tumor metabolism will also be studied. JI-101 is an inhibitor of new blood vessel growth that may provide benefit to patients with solid tumors that have failed standard therapeutic regimens.

开始日期2009-02-01

申办/合作机构

Jubilant Innovation Pte Ltd.

100 项与 JI-101 相关的临床结果

登录后查看更多信息

100 项与 JI-101 相关的转化医学

登录后查看更多信息

100 项与 JI-101 相关的专利（医药）

登录后查看更多信息

2

项与 JI-101 相关的文献（医药）

2015-12-01·Investigational New Drugs3区 · 医学

A pilot study of JI-101, an inhibitor of VEGFR-2, PDGFR-β, and EphB4 receptors, in combination with everolimus and as a single agent in an ovarian cancer expansion cohort

3区 · 医学

Article

作者: Boucher, Kenneth ; Agarwal, Neeraj ; Wade, Mark L ; Patel, Jesal ; Luebke, Aaron ; Sharma, Sunil ; Werner, Theresa L

JI-101 is an oral multi-kinase inhibitor that targets vascular endothelial growth factor receptor type 2 (VEGFR-2), platelet derived growth factor receptor β (PDGFR-β), and ephrin type-B receptor 4 (EphB4). None of the currently approved angiogenesis inhibitors have been reported to inhibit EphB4, and therefore, JI-101 has a novel mechanism of action. We conducted a pilot trial to assess the pharmacokinetics (PK), tolerability, and efficacy of JI-101 in combination with everolimus in advanced cancers, and pharmacodynamics (PD), tolerability, and efficacy of JI-101 in ovarian cancer. This was the first clinical study assessing anti-tumor activity of JI-101 in a combinatorial regimen. In the PK cohort, four patients received single agent 10 mg everolimus on day 1, 10 mg everolimus and 200 mg JI-101 combination on day 8, and single agent 200 mg JI-101 on day 15. In the PD cohort, eleven patients received single agent JI-101 at 200 mg twice daily for 28 day treatment cycles. JI-101 was well tolerated as a single agent and in combination with everolimus. No serious adverse events were observed. Common adverse events were hypertension, nausea, and abdominal pain. JI-101 increased exposure of everolimus by approximately 22%, suggestive of drug-drug interaction. The majority of patients had stable disease at their first set of restaging scans (two months), although no patients demonstrated a response to the drug per RECIST criteria. The novel mechanism of action of JI-101 is promising in ovarian cancer treatment and further prospective studies of this agent may be pursued in a less refractory patient population or in combination with cytotoxic chemotherapy.

2012-01-01·Arzneimittelforschung

Pharmacokinetics, Tissue Distribution and Identification of Putative Metabolites of JI-101 – A Novel Triple Kinase Inhibitor in Rats

Article

作者: Giri, S. ; Mohd, Z. ; Srinivas, N. ; Gilibili, R. ; Gurav, S. ; Mullangi, R. ; Jeniffer, S. ; Govindarajan, R.

JI-101, chemically 1-[1-(2-amino-pyridin-4-ylmethyl)-1H-indol-4-yl]-3-(5-bromo-2-methoxy-phenyl)-urea hydrochloride, is a novel orally active kinase inhibitor, which has shown potent in vitro and in vivo anticancer activity against a variety of cancer cell lines and xenografts. It is currently entering Phase II clinical development for the treatment of solid tumors. The aim of the study is to assess the metabolic stability of JI-101 in various pre-clinical and human liver microsomes, to identify the major CYPs (cytochrome β450) involved in the metabolism of JI-101 and identification of putative metabolites. We have also studied the pharmacokinetics, tissue distribution and excretion of JI-101 in Sprague Dawley rats. JI-101 was found to be stable in various liver microsomes tested. JI-101 is highly permeable and not a substrate for P-gp (permeability glycoprotein). JI-101 excreted through bile along with its mono- and di-hydroxy metabolites. Following oral administration, JI-101 was rapidly absorbed, reaching Cmax within 2 h. The t½ of JI-101 with intravenous and oral route was found to be 1.75 ± 0.79 and 2.66 ± 0.13 h, respectively. The Cl and Vd by intravenous route for JI-101 were found to be 13.0 ± 2.62 mL/min/kg and 2.11 ± 1.42 L/kg, respectively. The tissue distribution of JI-101 was extensive with rapid and preferred uptake into lung tissue. Overall, the oral bioavailability of JI-101 is 55% and the primary route of elimination for JI-101 is feces.

100 项与 JI-101 相关的药物交易

登录后查看更多信息

外链

KEGG	Wiki	ATC	Drug Bank
-	-	-	DB12744

研发状态

10 条进展最快的记录,

登录

后查看更多信息

适应症	最高研发状态	国家/地区	公司	日期
泌尿系统肿瘤	临床2期	美国	University of Utah	2011-05-20
泌尿系统肿瘤	临床2期	印度	Vanthys Pharmaceutical Development (P) Ltd.	2011-05-20
泌尿系统肿瘤	临床2期	美国	Huntsman Cancer Institute	2011-05-20
结肠癌	临床2期	美国	Jubilant Innovation Pte Ltd.	2010-09-01
卵巢癌	临床2期	美国	Jubilant Innovation Pte Ltd.	2010-09-01
RAS 突变结直肠癌	临床2期	美国	Jubilant Innovation Pte Ltd.	2010-09-01
晚期恶性实体瘤	临床2期	美国	Jubilant Innovation Pte Ltd.	2009-02-01
肿瘤	临床2期	-	Gilead Sciences, Inc.	-

登录后查看更多信息

临床结果

适应症

分期

评价

查看全部结果

研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT01149434 (CTgov)	临床1/2期	卵巢癌 \| RAS 突变结直肠癌 \| 结肠癌 \| 晚期恶性实体瘤	19	JI-101+Everolimus (Pharmacokinetic Arm)	簾遞遞餘鹹窪簾衊繭繭(憲膚鹹觸鏇夢遞鏇夢憲) = 廠積艱鏇襯衊觸窪憲簾顧選範顧壓網鬱壓襯壓 (廠餘糧築鬱鹹鹹淵願構, 遞觸壓壓衊網簾襯積網 ~ 憲窪製鹹齋蓋鹹簾觸衊) 更多	-	2014-09-25
NCT01149434 (CTgov)	临床1/2期	卵巢癌 \| RAS 突变结直肠癌 \| 结肠癌 \| 晚期恶性实体瘤	19	JI-101 (Pharmacodynamic Arm)	獵觸鏇繭選網觸鑰願蓋(夢觸夢築憲廠憲齋網顧) = 獵鹹鏇願鏇網鑰壓襯糧鹽窪鬱獵廠鬱蓋選遞鑰 (壓壓醖窪膚網艱餘壓鑰, 築淵襯廠壓範網製簾築 ~ 觸繭鑰淵構蓋鏇膚鬱夢) 更多	-	2014-09-25
NCT00842335 (CTgov)	临床1/2期	晚期恶性实体瘤	18	JI-101	選鏇壓觸網獵憲壓壓觸(糧鏇蓋積廠艱積簾鑰襯) = 鹽齋鏇積衊蓋構鏇築鏇繭觸顧淵鬱鑰膚獵窪觸 (鑰壓廠艱齋簾選糧鏇築, 網夢衊襯範憲壓襯淵製 ~ 鑰獵網膚遞衊鑰壓獵齋) 更多	-	2013-06-24