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

靶点

MR

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.

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

8

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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3

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

AbstractMineralocorticoid 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.

2017-06-01·The Journal of Clinical Pharmacology3区 · 医学

Journal of Clinical Pharmacology

3区 · 医学

Article

作者: Wang, Evan B. ; Dickinson, Gemma L. ; Chaudhary, Archana ; Waterhouse, Timothy H.

LY2623091 is a selective, orally active, nonsteroidal, competitive mineralocorticoid receptor antagonist that blocks the actions of aldosterone and other mineralocorticoid receptor ligands at the receptor level. The aim of this work was to explore and establish a population pharmacokinetic model, quantify the degree of interindividual variability, and identify significant disease-, patient-, and study-specific covariates that alter the disposition of LY2623091. The data included concentrations from 294 healthy subjects and patients with hypertension and/or chronic kidney disease (CKD), sampled in 5 phase 1 and 2 studies. The pharmacokinetics of LY2623091 was well described by a 2-compartment model with first-order absorption and elimination. Formulation (on oral bioavailability) as well as weight and age (both on apparent central volume of distribution) were found to be significant covariates. The relative bioavailability of the capsule formulation was 68.4% compared to that of the solution. Hypertension and CKD status were not significant covariates. The pharmacokinetic model suggests that given the same dose, patients with hypertension and/or CKD would receive a similar exposure compared to subjects without these disease conditions.

2015-09-01·Current Opinion in Nephrology and Hypertension3区 · 医学

Nonsteroidal antagonists of the mineralocorticoid receptor

3区 · 医学

Review

作者: Eitner, Frank ; Nowack, Christina ; Kolkhof, Peter

PURPOSE OF REVIEWThe broad clinical use of steroidal mineralocorticoid receptor antagonists (MRAs) is limited by the potential risk of inducing hyperkalemia when given on top of renin-angiotensin system blockade. Drug discovery campaigns have been launched aiming for the identification of nonsteroidal MRAs with an improved safety profile. This review analyses the evidence for the potential of improved safety profiles of nonsteroidal MRAs and the current landscape of clinical trials with nonsteroidal MRAs.RECENT FINDINGSAt least three novel nonsteroidal MRAs have reportedly demonstrated an improved therapeutic index (i.e. less risk for hyperkalemia) in comparison to steroidal antagonists in preclinical models. Five pharmaceutical companies have nonsteroidal MRAs in clinical development with a clear focus on the treatment of chronic kidney diseases. No clinical data have been published so far for MT-3995 (Mitsubishi), SC-3150 (Daiichi-Sankyo), LY2623091 (Eli Lilly) and PF-03882845 (Pfizer). In contrast, data from two clinical phase II trials are available for finerenone (Bayer) which demonstrated safety and efficacy in patients with heart failure and additional chronic kidney diseases, and significantly reduced albuminuria in patients with diabetic nephropathy. Neither hyperkalemia nor reductions in kidney function were limiting factors to its use.SUMMARYNovel, nonsteroidal MRAs are currently tested in clinical trials. Based on preclinical and first clinical data, these nonsteroidal MRAs might overcome the limitations of today's steroidal antagonists.

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	波多黎各	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	南非	Eli Lilly & Co.	2011-09-01
慢性肾病	临床2期	保加利亚	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	遞獵製窪齋選簾鹽積願(鏇構鑰夢構憲醖膚壓壓) = 簾廠廠壓餘鏇製糧獵鬱憲鑰蓋鑰簾構醖積艱鬱 (顧壓遞獵齋簾壓鹹襯夢, 積顧獵構積觸積鹹憲願 ~ 壓獵壓繭製窪艱淵鹹簾) 更多	-	2020-06-26
NCT02194465 (CTgov)	临床2期	原发性高血压	304	Placebo (Placebo)	繭蓋簾廠鹽觸積襯廠衊(製製觸淵繭衊遞鑰遞襯) = 齋鬱顧襯窪壓壓艱餘衊獵選廠糧齋餘窪繭衊構 (醖選顧觸壓構構廠願願, 壓繭鹽鏇築製鏇構鑰選 ~ 夢願膚願築製製遞艱齋) 更多	-	2020-06-26
				Placebo+LY2623091 (13 mg LY2623091)	繭蓋簾廠鹽觸積襯廠衊(製製觸淵繭衊遞鑰遞襯) = 獵遞獵夢憲夢鏇願製選獵選廠糧齋餘窪繭衊構 (醖選顧觸壓構構廠願願, 選齋衊遞積衊壓構鬱齋 ~ 糧糧淵壓鏇艱簾顧顧衊) 更多
NCT02300259 (CTgov)	临床1期	-	48	LY2623091 (LY2623091 (Group 1))	遞觸觸顧齋糧繭鑰憲選(齋窪艱壓遞醖醖憲鹹願) = 夢鏇鑰憲鏇築繭積鹽膚膚鹽觸鹹蓋築簾淵繭壓 (積膚顧壓顧壓遞膚鬱憲, 淵製積廠襯淵願鹽醖築 ~ 壓鹹憲構衊襯範積製淵) 更多	-	2020-06-26
				Itraconazole+LY2623091 (Itraconazole + LY2623091 (Group 1))	遞觸觸顧齋糧繭鑰憲選(齋窪艱壓遞醖醖憲鹹願) = 獵選積膚鑰獵餘醖鬱範膚鹽觸鹹蓋築簾淵繭壓 (積膚顧壓顧壓遞膚鬱憲, 齋壓簾顧製膚觸襯衊積 ~ 鹹構鹹壓簾鏇鏇鹹遞壓) 更多