BI-135585(BI-135585) - 药物靶点：11β-HSD1_在研适应症：2型糖尿病_专利_临床

概要

基本信息

药物类型

小分子化药

别名

Compound 11j (Vitae Pharmaceuticals)

+ [2]

靶点

11β-HSD1

作用机制

11β-HSD1抑制剂(11β-羟基类固醇脱氢酶-1抑制剂)

治疗领域

内分泌与代谢疾病

在研适应症

2型糖尿病

非在研适应症-

原研机构

Vitae Pharmaceuticals LLC

在研机构

Vitae Pharmaceuticals LLC

非在研机构

Boehringer Ingelheim GmbH

最高研发阶段临床1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C28H34N2O5

InChIKeyRYMUARXBHUNLAU-DZGIFAGBSA-N

CAS号1374032-89-9

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关联

5

项与 BI-135585 相关的临床试验

NCT01652742 / Completed临床1期

Pharmacokinetics and Pharmacodynamics of BI 135585 XX Administered as Oral Dose in Healthy Male Volunteers (Open-label, Single-dose Trial)

To investigate the pharmacokinetics and pharmacodynamics of BI 135585 XX following single dose administration.

开始日期2012-07-01

申办/合作机构

Boehringer Ingelheim GmbH

NCT01282970 / Completed临床1期

Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Multiple Rising Oral Doses (5 to 100 mg q.d. for 14 Days) of BI 135585 XX in Patients With Type 2 Diabetes Mellitus (Randomized, Double-blind Placebo-controlled Within Dose Groups)

The objective of this study is to investigate safety, tolerability, pharmacokinetics and pharmacodynamics of BI 135585 XX following multiple dose administration over 14 days

开始日期2011-02-01

申办/合作机构

Boehringer Ingelheim GmbH

NCT01291732 / Completed临床1期

Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Single Rising Oral Doses (12.5 mg, 50 mg, 200 mg) of BI 135585 XX (Tablet) in Chinese and Japanese Healthy Male Volunteers (Randomised, Double-blind,Placebo-controlled Within Dose Groups)

The Aim of the study is to evaluate safety, tolerability, pharmacokinetics and pharmacodynamics in Asian healthy males administered a single dose of BI 135585.

开始日期2011-02-01

申办/合作机构

Boehringer Ingelheim GmbH

100 项与 BI-135585 相关的临床结果

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100 项与 BI-135585 相关的转化医学

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100 项与 BI-135585 相关的专利（医药）

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3

项与 BI-135585 相关的文献（医药）

2017-07-01·Bioorganic & Medicinal Chemistry3区 · 医学

Discovery of BI 135585, an in vivo efficacious oxazinanone-based 11β hydroxysteroid dehydrogenase type 1 inhibitor

3区 · 医学

Article

作者: Himmelsbach, Frank ; Leftheris, Katerina ; Xu, Zhenrong ; Meng, Shi ; Kruk, Barbara A ; Zhao, Wei ; Johnson, Judith A ; Lala, Deepak ; Hamilton, Bradford ; Ye, Yuan-Jie ; Zhao, Yi ; Guo, Rong ; Schuler-Metz, Annette ; Singh, Suresh B ; Zhuang, Linghang ; McGeehan, Gerard M ; Claremon, David A ; Schauerte, Heike ; Krosky, Paula M ; Gregg, Richard ; Howard, Lamont ; Cacatian, Salvacion ; McKeever, Brian M ; Lindblom, Peter ; Tice, Colin M ; Bukhtiyarov, Yuri ; Panemangalore, Reshma ; Guo, Joan

A potent, in vivo efficacious 11β hydroxysteroid dehydrogenase type 1 (11β HSD1) inhibitor (11j) has been identified. Compound 11j inhibited 11β HSD1 activity in human adipocytes with an IC₅₀ of 4.3nM and in primary human adipose tissue with an IC₈₀ of 53nM. Oral administration of 11j to cynomolgus monkey inhibited 11β HSD1 activity in adipose tissue. Compound 11j exhibited >1000× selectivity over other hydroxysteroid dehydrogenases, displays desirable pharmacodynamic properties and entered human clinical trials in 2011.

2016-05-01·Diabetes, Obesity and Metabolism2区 · 医学

Safety, pharmacokinetics and pharmacodynamics of BI 135585, a selective 11β‐hydroxysteroid dehydrogenase‐1 (HSD1) inhibitor in humans: liver and adipose tissue 11β‐HSD1 inhibition after acute and multiple administrations over 2 weeks

2区 · 医学

Article

作者: Woerle, H.‐J. ; Jungnik, A. ; Freude, S. ; Rauch, T. ; Hamilton, B. ; Schölch, C. ; Huang, F. ; Graefe‐Mody, U. ; Heise, T.

AimsTo assess the safety and pharmacokinetic and pharmacodynamic characteristics of BI 135585, a selective 11β‐hydroxysteroid dehydrogenase‐1 (11β‐HSD1) inhibitor, after single‐ and repeated‐dose administration.MethodsThe single‐dose study included open‐label administration of 200 mg BI 135585 in healthy volunteers, while in the multiple‐dose study, we carried out randomized, double‐blind administration of 5–200 mg BI 135585 or placebo once daily over 14 days in patients with type 2 diabetes (T2DM). Assessments included 11β‐HSD1 inhibition in the liver (urinary tetrahydrocortisol (THF)/tetrahydrocotisone (THE) ratio) and in subcutaneous adipose tissue (AT) ex vivo and determination of hypothalamus‐pituitary‐adrenal (HPA) axis hormone levels.ResultsNo major safety issues occurred with BI 135585 administration. The HPA axis was mildly activated with slightly increased, but still normal adrenocorticotropic hormone levels, increased total urinary corticoid excretion but unchanged plasma cortisol levels. After multiple doses of 5–200 mg BI 135585, exposure (area under the curve) increased dose‐proportionally and half‐life was 55–65 h. The urinary THF/THE ratio decreased, indicating liver 11β‐HSD1 inhibition. Median 11β‐HSD1 enzyme inhibition in the AT reached 90% after a single dose of BI 135585, but was low (31% or lower) after 14 days of continuous treatment.ConclusionsBI 135585 was safe and well tolerated over 14 days and can be dosed once daily. Future studies are required to clarify the therapeutic potential of BI 135585 in view of its effects on 11β‐HSD1 inhibition in AT after single and multiple doses. Enzyme inhibition in the AT was not adequately predicted by the urinary THF/THE ratio.

2015-01-01·European Journal of Pharmacology3区 · 医学

Pharmacological characterization of the selective 11β-hydroxysteroid dehydrogenase 1 inhibitor, BI 135585, a clinical candidate for the treatment of type 2 diabetes

3区 · 医学

Article

作者: Claremon, David A ; Zhuang, Linghang ; Guo, Joan ; Lala, Deepak S ; Zhao, Yi ; Schuler-Metz, Annette ; Krosky, Paula ; Hamilton, Bradford S ; McGeehan, Gerard M ; Meng, Shi ; Nar, Herbert ; Guo, Rong ; Himmelsbach, Frank

To combat the increased morbidity and mortality associated with the developing diabetes epidemic new therapeutic interventions are desirable. Inhibition of intracellular cortisol generation from cortisone by blocking 11β-hydroxysteroid dehydrogenase 1 (11β-HSD1) has been shown to ameliorate the risk factors associated with the metabolic syndrome. A challenge in developing 11β-HSD1 inhibitors has been the species selectivity of small molecules, as many compounds are primate specific. Here we describe our strategy to identify potent selective 11β-HSD1 inhibitors while ensuring target engagement in key metabolic tissues, liver and fat. This strategy enabled the identification of the clinical candidate, BI 135585.

100 项与 BI-135585 相关的药物交易

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