LY-2623091(LY-2623091) - 药物靶点：MR_专利_临床

概要

基本信息

药物类型

小分子化药

别名

LY 2623091

靶点

MR

作用方式

拮抗剂

作用机制

MR拮抗剂(盐皮质激素受体拮抗剂)

治疗领域

心血管疾病泌尿生殖系统疾病

在研适应症-

非在研适应症

慢性肾病原发性高血压

原研机构

Eli Lilly & Co.

在研机构-

非在研机构

Eli Lilly & Co.

权益机构-

最高研发阶段无进展临床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/序列

分子式C30H30FN5O3

InChIKeyYPCLDHGBEKZGEB-RUDKWAFVSA-N

CAS号1162264-07-4

关联

7

项与 LY-2623091 相关的临床试验

NCT02300259

/ Completed临床1期

A Study to Determine the Effect of CYP3A Inhibition on the Pharmacokinetics of LY2623091 and the Effect of LY2623091 on the Pharmacokinetics of CYP3A Substrates in Healthy Subjects

The first purpose of this study is to evaluate the effect of itraconazole (and possibly diltiazem) on the amount of LY2623091 in the blood stream and how long the body takes to get rid of it.
The second purpose of the study is to evaluate the effect of LY2623091 on the amount of simvastatin (and possibly tadalafil) in the blood stream and how long the body takes to get rid of it.
The safety and tolerability of LY2623091 when given with itraconazole, simvastatin and diltiazem or tadalafil will be evaluated.
There will be three groups of participants in this study. Results from Groups 1 and 2 will be analyzed during the study to determine whether to enroll participants in Group 3 or 4. The study is expected to last up to 40 days from the first dose to follow-up (inclusive). Screening may occur up to 28 days prior to enrollment.

开始日期2014-11-01

申办/合作机构

Eli Lilly & Co.

NCT02242981

/ Completed临床1期

Disposition of [14C]-LY2623091 Following Oral Administration in Healthy Subjects

This type of study is called a radiolabeled study. For this study, LY2623091 (study drug) has been specially prepared to contain radiolabeled carbon [^14C]. [^14C] is a naturally occurring radioactive form of the element, carbon. This study will increase understanding about how the drug appears in the blood, urine, and stool after it is administered to healthy participants. Information about any side effects that may occur will also be collected. This study will last up to 22 days for each participant, not including screening. Screening is required within 28 days prior to enrollment

开始日期2014-09-01

申办/合作机构

Eli Lilly & Co.

NCT02194465

/ Completed临床2期

A Randomized, Placebo-Controlled, Double-Blinded, Parallel, Phase 2a Study to Evaluate the Safety and Efficacy of LY2623091 in Patients With Primary Hypertension

The main purpose of this study is to evaluate the safety and effectiveness of the study drug known as LY2623091 in participants with high blood pressure.

开始日期2014-08-01

申办/合作机构

Eli Lilly & Co.

100 项与 LY-2623091 相关的临床结果

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100 项与 LY-2623091 相关的转化医学

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100 项与 LY-2623091 相关的专利（医药）

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6

项与 LY-2623091 相关的文献（医药）

2021-05-01·Drug development research3区 · 医学

Role of mineralocorticoid receptor antagonists in kidney diseases

3区 · 医学

Review

作者: Jain, Mukul ; Joharapurkar, Amit ; Patel, Vishal

Abstract:

Mineralocorticoid receptor (MR) antagonists, for example, spironolactone and eplerenone, are in clinical use to treat hypertension. Increasing evidence suggests that mineralocorticoid receptor activation causes the pathogenesis and progression of chronic kidney disease. Aldosterone‐induced MR activation increases inflammation, fibrosis, and oxidative stress in the kidney. MR antagonists (MRAs) have demonstrated therapeutic actions in chronic kidney disease (CKD), diabetic nephropathy (DN), renal fibrosis, and drug‐induced renal injury in preclinical and clinical studies. We have summarized and discussed these studies in this review. The nonsteroidal MRA, esaxerenone, recently received approval for the treatment of hypertension. It has also shown a positive therapeutic effect in phase 3 clinical trials in patients with DN. Other nonsteroidal MRA such as apararenone, finerenone, AZD9977, and LY2623091 are in different clinical trials in patients with hypertension suffering from renal or hepatic fibrotic diseases. Hyperkalemia associated with MRA therapy has frequently led to the discontinuation of the treatment. The new generation nonsteroidal MRAs like esaxerenone are less likely to cause hyperkalemia at therapeutic doses. It appears that the nonsteroidal MRAs can provide optimum therapeutic benefit for patients suffering from kidney diseases.

2020-01-01·European journal of medicinal chemistry1区 · 医学

Structural attributes influencing unbound tissue distribution

1区 · 医学

Article

作者: Filipski, Kevin J ; Di, Li ; Litchfield, John ; Atkinson, Karen ; Lin, Jian ; Keefer, Christopher ; Kalgutkar, Amit S ; Orozco, Christine C ; Chang, George ; Tess, David ; Mongillo, Robert K ; Riccardi, Keith ; Ryu, Sangwoo ; Scott, Dennis

Unbound tissue-to-plasma partition coefficients (K_puu) were determined for 56 structurally diverse compounds in rats following intravenous infusion. Five tissues were included in the study: white adipose, brain, heart, liver, and skeletal muscle. The rank ordering of the median tissue K_puu values was: liver (4.5) > heart (1.8) > adipose (1.2) > skeletal muscle (0.6) > brain (0.05), with liver being most enriched and brain most impaired. The median K_puu values of acids and zwitterions were lower than those of bases and neutrals in all tissues but liver. Selective tissue distribution was observed, dependent upon chemotype, which demonstrated the feasibility of targeting or restricting drug exposure in certain tissues through rational design. Physicochemical attributes for K_puu were identified using recursive partitioning, which further classified compounds with enriched or impaired tissue distribution. The attributes identified provided valuable insight on design principles for asymmetric tissue distribution to improve efficacy or reduce toxicity.

2017-11-01·International journal of pharmacokinetics

Physiologically Based Pharmacokinetic Modeling to Understand the Observed Drug–Drug Interaction of LY2623091 with CYP3A Inhibitors Itraconazole and Diltiazem

作者: Posada, Maria M ; Dickinson, Gemma L ; Hall, Stephen D ; Chaudhary, Archana ; Phillips, Diane L

Aims: Drug–drug interaction studies were used to estimate CYP3A4-dependent clearance of LY2623091. Methods: in a cross-over design, healthy adults received a single 6-mg dose of LY2623091 at baseline. Itraconazole (200 mg twice on day 1 then daily × 19 days; n = 16) and diltiazem (240 mg Extended Release daily × 13 days; n = 16) were given. On days 6 and 4, respectively, LY2623091 was dosed 1 h after itraconazole/diltiazem. Pharmacokinetic samples were obtained and static and dynamic models were used to assess interaction. Results: Area under the concentration–time curve for LY2623091 increased 2.2-fold with itraconazole and 1.4-fold with diltiazem. Maximum plasma concentration did not change. The physiologically based pharmacokinetic model overpredicted itraconazole and hydroxy–itraconazole concentrations. Extraction by CYP3A4 was ∼0.5; gut wall extraction was negligible. Conclusion: Interaction risk requires early clinical assessment to quantify the candidate drug. (Clinical trial registration number: NCT02300259). Data deposition: deposition pending.

100 项与 LY-2623091 相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
-	-	-	DB15367

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
原发性高血压	临床2期	美国	Eli Lilly & Co.	2014-08-01
原发性高血压	临床2期	加拿大	Eli Lilly & Co.	2014-08-01
慢性肾病	临床2期	保加利亚	Eli Lilly & Co.	2011-09-01
慢性肾病	临床2期	南非	Eli Lilly & Co.	2011-09-01

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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


NCT02242981 (CTgov)	临床1期	-	6	LY2623091	醖襯製艱齋艱鬱鹽餘積(鏇窪獵鏇鑰遞鹽憲膚齋) = 鏇襯淵衊淵選糧遞艱簾顧襯壓鹹獵繭糧觸衊製 (選構鹹構鏇鹹蓋鹽網顧, 4.27) 更多	-	2020-06-26
NCT02194465 (CTgov)	临床2期	原发性高血压	304	Placebo (Placebo)	夢膚鏇鹽選簾鑰壓網網(範餘網衊窪襯糧繭襯膚) = 構鬱鹹襯鏇積襯遞鏇構蓋製積襯選鬱夢廠築範 (衊鏇壓壓鹽憲夢網獵簾, 11.6) 更多	-	2020-06-26
				Placebo+LY2623091 (13 mg LY2623091)	夢膚鏇鹽選簾鑰壓網網(範餘網衊窪襯糧繭襯膚) = 獵獵選網鹹鹹遞構顧網蓋製積襯選鬱夢廠築範 (衊鏇壓壓鹽憲夢網獵簾, 12.3) 更多
NCT02300259 (CTgov)	临床1期	-	48	LY2623091 (LY2623091 (Group 1))	獵齋觸積遞夢窪選鑰醖(製築鬱簾築簾觸網鹹遞) = 衊遞網夢鬱醖獵鹹範範齋鹹餘膚壓積衊遞衊範 (艱衊遞製醖夢獵顧簾願, 21) 更多	-	2020-06-26
				itraconazole+LY2623091 (Itraconazole + LY2623091 (Group 1))	獵齋觸積遞夢窪選鑰醖(製築鬱簾築簾觸網鹹遞) = 鹽願夢鬱範網醖範鏇糧齋鹹餘膚壓積衊遞衊範 (艱衊遞製醖夢獵顧簾願, 27) 更多