TT-701(TT-701) - 药物靶点：AR_在研适应症：终末期肾脏病_专利_临床

A Randomized, Double-blind, Placebo-controlled Dose-ranging Study of OPK-88004 Once-a-day Dosing for 16 Weeks in Men With Signs and Symptoms of Benign Prostatic Hyperplasia

This study will evaluate the safety and effectiveness of different doses of OPK-88004 compared to placebo on serum PSA compared to placebo in men with benign prostatic hyperplasia (BPH).

开始日期2018-02-21

申办/合作机构

OPKO Health, Inc.

NCT02499497

/ Completed临床2期IIT

A Selective Androgen Receptor Modulator for Symptom Management in Prostate Cancer

This research study is studying the use of a targeted therapy called LY SARM, which is an investigational drug from a new class of molecules called Selective Androgen Receptor Modulators (SARMs) as a possible improvement in quality of life for participants who have undergone radical prostatectomy. Androgens are a group of hormones that play a role in male traits and reproductive activity.
The names of the study interventions involved in this study are:
- LY2452473

开始日期2016-02-29

申办/合作机构

Dana-Farber Cancer Institute, Inc.

NCT01275157

/ Completed临床1期

Disposition of [14C]-LY2452473 Following Oral Administration in Healthy Human Subjects

This is a single dose study of radiolabeled [14C]-LY2452473 in healthy male volunteers to study the absorption, distribution, metabolism, and elimination of LY2452473.
This study is for research purposes only and is not intended to treat any medical condition.

开始日期2011-01-01

申办/合作机构

Eli Lilly & Co.

100 项与 TT-701 相关的临床结果

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100 项与 TT-701 相关的转化医学

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100 项与 TT-701 相关的专利（医药）

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15

项与 TT-701 相关的文献（医药）

2025-02-01·Analytical and Bioanalytical Chemistry

LC-HRMS screening procedure for the detection of 11 different classes of prohibited substances in dried urine spots for doping control purposes

Article

作者: Van Eenoo, Peter ; Pizzolato, Francesca ; Honesová, Lenka ; Gmeiner, Günter ; Tsivou, Maria ; Mazzarino, Monica

Dried urine spots have recently been proposed as an alternative matrix in the anti-doping field. Drying urine may open the opportunity to limit microbial and thermal degradation of the prohibited substances during transportation to the anti-doping laboratories without the need for refrigeration or freezing. In this study, a multi-targeted initial testing procedure was developed for the determination of 237 prohibited drugs/metabolites from 11 different classes in dried urine spots. The comparability between two different microsampling techniques (i.e., Whatman^® FTA DMPK-C cards and Mitra^® tips) was evaluated. The developed method was then used to evaluate the stability of the target compounds in urine for 7 days under different environmental conditions to simulate the transportation of the urine samples from the collection sites to anti-doping laboratories. Sample preparation consists of (i) extraction of the analytes from the collection device using a mixture of acetonitrile/methanol (1/1) for 30 min at 40 °C, (ii) enzymatic hydrolysis, and (iii) sample concentration by solid-phase extraction. Analysis was performed using liquid chromatography coupled to high-resolution mass spectrometry. The entire workflow was validated in terms of specificity (analytes were distinguishable from the matrix interferences), sensitivity (only with the Mitra^® tips the limits of detection comply with the World Anti-Doping Agency's requirements for the majority of the target compounds), carry-over (no signals in the negative urine injected after the positive urine), matrix effect (16-28% for Mitra^® tips and 22-35% for DMPK-C cards), and extraction yield (Mitra^® tips: 51-88%; DMPK-C cards: 40-76%). As proof of concept, authentic urine samples were analyzed: results obtained in dried urine were compared with those of fluid urine, providing good agreement. Stability studies showed that the target compounds were stable for the whole duration of the study (7 days) at -20 and 4 °C in both fluid and dried urine. At 50 °C or at 20-25 °C, several thiazide-based compounds were completely degraded to their degradation product in the first 24 h or after 3-4 days in fluid urine, whereas in dried urine the compounds were detectable for the entire duration of the study.

2024-11-01·Biomedicine & Pharmacotherapy

Polypharmacological profiling across protein target families and cellular pathways using the multiplexed cell-based assay platform safetyProfiler reveals efficacy, potency and side effects of drugs

Article

作者: Popović, Lukša ; Wehr, Michael C. ; Rossner, Moritz J. ; Palladino, Giulia ; Brankatschk, Ben ; Rossner, Moritz J ; Wehr, Michael C

Selectivity profiling is key for assessing the pharmacological properties of multi-target drugs. We have developed a cell-based and barcoded assay encompassing ten druggable targets, including G protein-coupled receptors (GPCRs), receptor tyrosine kinases (RTKs), nuclear receptors, a protease as well as their key downstream pathways and profiled 17 drugs in living cells for efficacy, potency, and side effects. Notably, this multiplex assay, termed safetyProfiler assay, enabled the simultaneous assessment of multiple target and pathway activities, shedding light on the polypharmacological profile of compounds. For example, the neuroleptics clozapine, paliperidone, and risperidone potently inhibited primary targets DRD2 and HTR2A as well as cAMP and calcium pathways. However, while paliperidone and risperidone also potently inhibited the secondary target ADRA1A and mitogen-activated protein kinase (MAPK) downstream pathways, clozapine only exhibited mild antagonistic effects on ADRA1A and lacked MAPK inhibition downstream of DRD2 and HTR2A. Furthermore, we present data on the selectivity for bazedoxifene, an estrogen receptor antagonist currently undergoing clinical phase 2 trials for breast cancer, on MAPK signaling. Additionally, precise potency data for LY2452473, an androgen receptor antagonist, that completed a phase 2 clinical trial for prostate cancer, are presented. The non-selective kinase inhibitor staurosporine was observed to potently inactivate the two RTKs EGFR and ERBB4 as well as MAPK signaling, while eliciting stress-related cAMP responses. Our findings underscore the value of comprehensive profiling in elucidating the pharmacological properties of established and novel therapeutics, thereby facilitating the development of novel multi-target drugs with enhanced efficacy and selectivity.

2023-05-15·Rapid Communications in Mass Spectrometry

Metabolic study of selective androgen receptor modulator LY2452473 in thoroughbred horses for doping control

Article

作者: Karatt, Tajudheen K. ; Subhahar, Michael Benedict ; Caveney, Marina Rodriguez ; Philip, Moses ; Laya, Saraswathy ; Sathiq, M. Anwar ; M.P, Muhammed Ajeebsanu ; Graiban, Fatma Mohammed ; Karakka Kal, Abdul Khader

RationaleSince 2010, there has been an increasing number of adverse analytical findings related to selective androgen receptor modulators (SARMs) in competitive sports. It emphasizes the importance of comprehensive doping control analytical procedures that are capable of detecting SARM misuse.MethodsIn this study, it is described how LY2452473, a SARM, was metabolized in thoroughbred horses after a single‐dose oral administration and in vitro with equine liver microsome preparations. An investigation of the metabolism of LY2452473 in horses' urine, plasma, and hair matrices was carried out during the study. The plausible structures of the detected metabolites were postulated using high‐performance liquid chromatography‐high resolution mass spectrometry.ResultsUnder the experimental conditions 15 metabolites (12 phase I and three conjugates of phase I) were detected (M1–M15). The major phase I metabolites identified were formed by hydroxylation. Side‐chain dissociated and methylated metabolites were also detected. In phase II, the glucuronic acid and sulfonic acid conjugates of hydroxy LY2452473 were detected as the major metabolites. In vitro analysis has confirmed the presence of all metabolites found in vivo except for the methylated analogs M11 and M12. A peak concentration of LY2452473 (0.5 pg/mg) in proximal hair segments was achieved 4 weeks after administration, according to hair analysis.ConclusionsData obtained will aid in identifying LY2452473 and related substances faster. Furthermore, the results will assist in checking for the illegal use of these substances in competitive sports.

100 项与 TT-701 相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
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研发状态

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适应症	最高研发状态	国家/地区	公司	日期
终末期肾脏病	临床1期	美国	Prolor Biotech Ltd.	2022-08-22
勃起功能障碍	临床1期	美国	Eli Lilly & Co.	2010-10-01
前列腺增生症	临床前	美国	OPKO Health, Inc.	2018-02-21

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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


NCT02499497 (CTgov)	临床2期	前列腺癌	114	Placebo (Placebo)	壓範鏇齋餘獵艱醖餘夢(膚積糧選廠鬱構簾網夢) = 廠鑰鏇鏇膚繭襯觸衊膚壓鬱願獵蓋鑰餘艱廠獵 (簾艱獵積夢選繭構淵壓, 範範齋膚餘鏇願築膚繭 ~ 夢簾蓋餘淵顧鹽廠鹽壓) 更多	-	2021-09-28
				LY2452473 (LY2452473 Dose 1)	壓範鏇齋餘獵艱醖餘夢(膚積糧選廠鬱構簾網夢) = 鏇觸製鑰築獵壓醖遞餘壓鬱願獵蓋鑰餘艱廠獵 (簾艱獵積夢選繭構淵壓, 醖鹽糧齋鏇範鹽積壓膚 ~ 鬱遞獵構築餘願襯製蓋) 更多
NCT01160289 (CTgov)	临床2期	勃起功能障碍	410	LY2452473+Tadalafil (1 mg LY2452473 and 5 mg Tadalafil)	鬱願鹹憲築襯衊鬱餘獵(顧壓窪製簾鑰積膚鬱憲) = 顧鬱鏇選壓鑰繭餘繭觸築廠網觸願製顧鏇構壓 (遞遞鬱夢糧積範獵繭網, 獵餘廠膚獵膚醖壓艱鹹 ~ 構窪築襯憲衊網襯夢築) 更多	-	2019-04-09
				LY2452473+Tadalafil (5 mg LY2452473 and 5 mg Tadalafil)	鬱願鹹憲築襯衊鬱餘獵(顧壓窪製簾鑰積膚鬱憲) = 網醖廠鏇鹹構願艱蓋鑰築廠網觸願製顧鏇構壓 (遞遞鬱夢糧積範獵繭網, 廠鑰願衊遞製鏇製繭獵 ~ 鏇繭夢範艱積壓構網衊) 更多