Derenofylline(Derenofylline) - 药物靶点：A1R_专利_临床

概要

基本信息

药物类型

小分子化药

别名

靶点

A1R

作用机制

A1R拮抗剂(腺苷A1受体拮抗剂)

治疗领域

肿瘤心血管疾病泌尿生殖系统疾病

在研适应症-

非在研适应症

急性失代偿性心力衰竭心脏衰竭肾细胞癌

原研机构

Abbott Laboratories

在研机构-

非在研机构

Solvay Pharmaceuticals, Inc.

Solvay SA

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

结构

分子式C18H20N4O

InChIKeyRBZNJGHIKXAKQE-HDJSIYSDSA-N

CAS号251945-92-3

关联

3

项与 Derenofylline 相关的临床试验

NCT00744341 / Terminated临床2期

A Double-Blind, Placebo-Controlled, Randomized, Multi-Center, Dose-Finding Study of SLV320, a Selective A1 Adenosine Receptor Antagonist, to Evaluate the Effect on Renal Function and Safety in Subjects Hospitalized With Acute Decompensated Heart Failure and Renal Dysfunction (Reno-Defend 1)

The purpose of this study is to determine the efficacy and safety of IV SLV320 in acute heart failure patients with renal dysfunction.

开始日期2009-02-01

申办/合作机构

Solvay Pharmaceuticals, Inc.

NCT00568009 / TerminatedN/A

Randomized, Double-Blind, Placebo-Controlled, Multi-Center, Sequential Cohort Study to Evaluate the Effect of SLV320 in Addition to Chronic Furosemide Treatment on Renal Function in Subjects With Congestive Heart Failure and Impaired Renal Function

This is a randomized, double-blind, placebo-controlled, multi-center, sequential cohort study in subjects with congestive heart failure (CHF) and impaired renal function who are on stable furosemide treatment (³ 40 mg daily). A total of 50 subjects will be randomized to each increasing dose level of SLV320 or placebo in a sequential fashion.

开始日期2007-10-01

申办/合作机构

Solvay Pharmaceuticals, Inc.

[+1]

NCT00160134 / Completed临床2期

A Randomized, Placebo-Controlled, Double-Blind, Multi-Center, Parallel Group, Single Dose Study to Evaluate Cardiac Hemodynamics and Safety During Right Heart Catheterization of Three IV Doses of SLV320 in Subjects With Congestive Heart Failure Requiring Diuretic Treatment

The study is a randomized, placebo controlled, multi-center, single dose study to evaluate cardiac hemodynamics and safety of iv SLV320 in 110 subjects with congestive heart failure requiring diuretic treatment. Each subject will receive one dose of SLV320 or placebo or furosemide. The study consists of three visits (or study days when in-subjects are included). Ambulatory subjects will be in hospital for two nights and one day.

开始日期2005-01-01

申办/合作机构

Solvay Pharmaceuticals, Inc.

100 项与 Derenofylline 相关的临床结果

登录后查看更多信息

100 项与 Derenofylline 相关的转化医学

登录后查看更多信息

100 项与 Derenofylline 相关的专利（医药）

登录后查看更多信息

6

项与 Derenofylline 相关的文献（医药）

2021-08-01·Pharmacology Research & Perspectives4区 · 医学

Effects of sevoflurane and adenosine receptor antagonist on the sugammadex‐induced recovery from rocuronium‐induced neuromuscular blockade in rodent phrenic nerve–hemidiaphragm tissue specimens

4区 · 医学

ArticleOA

作者: Kim, Yong Beom ; In, Junyong ; Park, Chungon ; Choi, Hey‐Ran ; Yang, Hong‐Seuk ; Choi, Jae‐Moon

AbstractSevoflurane affects on the A1 receptor in the central nervous system and potentiates the action of neuromuscular blocking agents. In the present study, we investigated whether sevoflurane (SEVO) has the ability to potentiate the neuromuscular blocking effect of rocuronium and if the specific antagonist of adenosine receptor (SLV320) can reverse this effect. In this study, phrenic nerve–hemidiaphragm tissue specimens were obtained from 40 Sprague–Dawley (SD) rats. The specimens were immersed in an organ bath filled with Krebs buffer and stimulated by a train‐of‐four (TOF) pattern using indirect supramaximal stimulation at 20 s intervals. The specimens were randomly allocated to control, 2‐chloroadenosine (CADO), SEVO, or SLV320 + SEVO groups. In the CADO and SLV320 + SEVO groups, CADO and SLV320 were added to the organ bath from the start to a concentration of 10 μM and 10 nM, respectively. We then proceeded with rocuronium‐induced blockade of >95% depression of the first twitch tension of TOF (T1) and TOF ratio (TOFR). In the SEVO and SLV320 + SEVO groups, SEVO was added to the Krebs buffer solution to concentration of 400–500 μM for 10 min. Sugammadex‐induced T1 and TOFR recovery was monitored for 30 min until >95% of T1 and >0.9 of TOFR were confirmed, and the recovery pattern was compared by plotting these data. T1 recovery in the SEVO and CADO groups was significantly delayed compared with the control and SLV320 + SEVO groups (p < .05). In conclusion, sevoflurane affects on the A1 receptor at the neuromuscular junction and delays sugammadex‐induced recovery from neuromuscular blockade.

2018-12-01·Purinergic Signalling3区 · 医学

Adenosine enhances cisplatin sensitivity in human ovarian cancer cells

3区 · 医学

Article

作者: Kassack, Matthias U ; Brockmann, Nicole ; Sureechatchaiyan, Parichat ; Hamacher, Alexandra ; Stork, Bjoern

Ovarian cancer is the deadliest gynecologic cancer due to lack of early effective diagnosis and development of resistance to platinum-based chemotherapy. Several studies reported that adenosine concentrations are higher in tumor microenvironment than in non-tumor tissue. This finding inspired us to study the role of adenosine in ovarian cancer cells and to investigate if adenosine pathways offer new treatment options urgently needed to prevent or overcome chemoresistance. The ovarian cancer cell lines HEY, A2780, and its cisplatin-resistant subline A2780CisR were used in this study. Expression and functional activity of adenosine receptors were investigated by RT-PCR, Western blotting, and cAMP assay. A1 and A2B adenosine receptors were expressed and functionally active in all three cell lines. Adenosine showed moderate cytotoxicity (MTT-IC₅₀ values were between 700 and 900 μM) and induced apoptosis in a concentration-dependent manner by increasing levels of sub-G1 and cleaved PARP. Apoptosis was diminished by QVD-OPh, confirming caspase-dependent induction of apoptosis. Forty-eight hours pre-incubation of adenosine prior to cisplatin significantly enhanced cisplatin-induced cytotoxicity in a synergistic manner and increased apoptosis. SLV320 or PSB603, selective A1 and A2B antagonists, was not able to inhibit adenosine-induced increase in cisplatin cytotoxicity or apoptosis whereas dipyridamole, a nucleoside transporter inhibitor, completely abrogated both effects. Mechanistically, adenosine increased pAMPK and reduced pS6K which was prevented by dipyridamole. In conclusion, application of adenosine prior to cisplatin could be a new therapeutic option to increase the potency of cisplatin in a synergistic manner and thus overcome platinum resistance in ovarian cancer.

2011-06-01·American Heart Journal2区 · 医学

Rationale, design, and results from RENO-DEFEND 1: A randomized, dose-finding study of the selective A1 adenosine antagonist SLV320 in patients hospitalized with acute heart failure

2区 · 医学

Article

作者: Dmitri Kazei ; Aldo P. Maggioni ; Mandeep Mehra ; Gerasimos Filippatos ; Prasad Turlapaty ; Peter S. Pang ; Mihai Gheorghiade ; Jayne Middlebrooks

BACKGROUNDBaseline renal impairment as well as worsening renal function during hospitalization is associated with worse short- and long-term outcomes in patients hospitalized for acute heart failure (AHF). We hypothesized that selective A1 adenosine receptor blockade would induce natriuresis while preserving renal function in AHF patients with renal dysfunction.METHODSA phase II, randomized, double-blind, placebo-controlled, parallel group, multicenter study to evaluate the efficacy and safety of 2.5, 7.5, 15, and 30 mg/d SLV320 (1 hour intravenous infusions of 1.25, 3.75, 7.5, and 15 mg SLV320, every 12 hours for 3 days [a total of 6 doses] in addition to standard therapy) in subjects hospitalized with AHF and renal impairment who meet all inclusion/exclusion criteria. The study planned to enroll 450 subjects, with 90 subjects allocated equally to each treatment arm.RESULTSThe study was terminated early. The decision, which was unrelated to the study conduct or results, with a total of 46 subjects randomized. Of those randomized, 6:8:8:8 and 6 patients, respectively, completed the study in each of the dosing subgroups, with placebo as the fifth group. For the 1.25-mg study group, the mean age was 73 years; mean (SD) systolic blood pressure (SBP), 128.5 (16.2); heart rate, 80.8 (25.0); brain natriuretic peptide, 969.7 (571.28); creatinine (μmol/L), 149.7 (41.0); cystatin C, 1.468 (0.2777); estimated glomerular filtration rate, 33.8 (7.913); and blood urea nitrogen, 12.1 (2.9), with roughly similar values in each treatment arm. No seizures were reported during the study. Eight patients died during the study, none of whom were associated with the study drug per an independent, blinded, data safety monitoring board.CONCLUSIONBecause of the limited number of subjects and variability observed in the results, no definite conclusions can be made regarding the efficacy and safety of SLV320.

100 项与 Derenofylline 相关的药物交易

登录后查看更多信息

外链

KEGG	Wiki	ATC	Drug Bank
-	-	-	DB12446

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
肾细胞癌	临床2期	丹麦	Solvay Pharmaceuticals, Inc.	2009-02-01
肾细胞癌	临床2期	意大利	Solvay Pharmaceuticals, Inc.	2009-02-01
肾细胞癌	临床2期	波兰	Solvay Pharmaceuticals, Inc.	2009-02-01
肾细胞癌	临床2期	俄罗斯	Solvay Pharmaceuticals, Inc.	2009-02-01
肾细胞癌	临床2期	加拿大	Solvay Pharmaceuticals, Inc.	2009-02-01
肾细胞癌	临床2期	美国	Solvay Pharmaceuticals, Inc.	2009-02-01
肾细胞癌	临床2期	法国	Solvay Pharmaceuticals, Inc.	2009-02-01
肾细胞癌	临床2期	罗马尼亚	Solvay Pharmaceuticals, Inc.	2009-02-01
肾细胞癌	临床2期	德国	Solvay Pharmaceuticals, Inc.	2009-02-01
心脏衰竭	临床2期	美国	Solvay SA	-