Lanopepden mesylate(Lanopepden mesylate) - 药物靶点：def_专利_临床

概要

基本信息

药物类型

小分子化药

别名

Lanopepden、Lanopepden mesylate (USAN)、12M6KFD07E

+ [5]

靶点

def

作用机制

def抑制剂(肽脱甲酰基酶抑制剂)

治疗领域

感染皮肤和肌肉骨骼疾病

在研适应症-

非在研适应症

细菌感染皮肤和皮肤结构感染细菌性皮肤疾病

原研机构

GSK Plc

在研机构-

非在研机构

GSK Plc

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-

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结构

分子式C22H34FN7O4

InChIKeySWHNZGMQMGFQGW-MSOLQXFVSA-N

CAS号1152107-25-9

关联

9

项与 Lanopepden mesylate 相关的临床试验

NCT01803399 / Withdrawn临床1期

A Phase I, Randomized, Partially Blinded, Placebo- and Moxifloxacin-Controlled, 4-Period Crossover Study to Evaluate the Effect of GSK1322322 on Cardiac Conduction as Assessed by 12-lead Electrocardiogram in Healthy Volunteers (PDF112166)

This is a randomized, partially-blinded, placebo and moxifloxacin-controlled, single dose, 4-period, balanced crossover study. The primary objective of this study is to separately assess the effects of a therapeutic and supratherapeutic dose of GSK1322322 on the cardiac conduction (corrected QT interval [QTc]) compared with placebo in eligible healthy male and female subjects. Avelox (moxifloxacin hydrochloride) will be used as an open-label positive control in order to validate the sensitivity of the study in detecting QTc change. Approximately 56 healthy subjects will participate in the study for approximately 9 weeks i.e. 30 day Screening period, 4-week Treatment period, and a 7-10 day Follow-up period. There will be 4 treatment periods separated by at least 1 week. Subjects will be admitted to the clinical unit on Day -1 of each dosing period. Each subject will receive each of the four treatment sequences (GSK1322322 1200 milligram [mg] intravenous [IV] over 60 minutes x 1 dose, GSK1322322 3000 mg IV over 60 minutes x 1 dose, GSK1322322 Placebo IV over 60 minutes x 1 dose, moxifloxacin 400 mg administered orally x 1 dose) on Day 1 of each Treatment period in a randomized fashion. Twelve-lead electrocardiogram (ECG), continuous Holter monitoring, laboratory tests, vital sign measurements, and serial pharmacokinetic samples will be collected for up to 24 hours following each treatment. If no clinically significant abnormalities are noted, subjects will be discharged from the clinical research unit after the completion of all assessments on Day 2 in each period and return approximately one week later for the next dosing period. Each individual subject will follow the same dosing schedule at every period. A Follow-up visit will be conducted 7-10 days after administration of the last dose of study medication in treatment period 4.

开始日期2014-08-01

申办/合作机构

GSK Plc

NCT01953809 / Withdrawn临床1期

A Phase 1, Randomized, Single Blind Study to Evaluate the Pharmacokinetics, Pharmacodynamics, and Safety of an Oral Contraceptive Containing Norethindrone and Ethinyl Estradiol When Co-administered With GSK1322322 in Healthy Adult Women of Childbearing Age Who Are of Non-Childbearing Potential Due to Surgical Sterilization or IUD Placement (PDF112163)

This study is being conducted to confirm that GSK1322322 has no negative impact on hormone levels and contraceptive efficacy when co-administered with a frequently prescribed oral contraceptive thereby to facilitate the use of GSK1322322 in women of child-bearing potential receiving oral contraceptive (OC) pre-infection. This study is designed to investigate steady-state plasma ethinyl estradiol (EE) and norethindrone (NE) pharmacokinetic (PK) following administration of Ortho-Novum (EE/NE) 1 tablet every 24 hours (q24h) fed with and without GSK1322322 1500 milligram (mg) q12h fed. Each subject will participate in the study for approximately 12 weeks: a 30 day screening period, 4-week run-in period, three 7 day treatment periods, and a 3-5 day follow-up period. The study is planned to enroll approximately 24 subjects (18 active/6 placebo).

开始日期2014-08-01

申办/合作机构

GSK Plc

NCT01818011 / Terminated临床1期

A Three-Part Phase I, Open-Label, Single Ascending Dose, and A Single-Blind, Placebo-Controlled, Repeat Dose Study to Assess the Safety, Tolerability, Pharmacokinetics, and Relative Bioavailability of Intravenous and Oral GSK1322322 in Healthy Volunteers and Healthy Male Japanese Subjects

The primary objectives of this study are to assess the safety, tolerability and pharmacokinetics of GSK1322322 following intravenous (IV) and oral administration. GSK1322322 shows broad spectrum antibacterial activity against pathogens involved in respiratory tract infections as well as methicillin-resistant S. Aureus (MRSA).
This study consists of three parts (Part A, Part B and Part C). The results from Part A of this study will enable use of large-scale, commercial tablets produced for administration to patients in pivotal clinical trials of GSK1322322. The results from Parts B and C will support enrolment of Japanese subjects in future clinical studies. Additionally, the results will support the dose selection for further clinical development of GSK1322322 in hospitalized patients with severe bacterial infections in Japan and other Asian populations.
In Part A, subjects will undergo screening, 4 treatment periods receiving single dose of each of: 1500 mg Initial, fit-for-purpose tablet (product code AP), 1500 mg Over granulated tablet (product code AR), and the 1500 mg and 2000 mg of intended commercial tablets (product code AU).
In Part B of the study subjects will undergo screening, and be randomized to receive 3 doses of GSK1322322 oral cohort (100 mg, 1500 mg and 2000 mg) or IV cohort (600 mg, 900 mg and 1200 mg) each in 3 treatment periods.
Part C will be a single-blind, placebo-controlled, repeat dose study of GSK1322322 in healthy Japanese male subjects. GSK1322322 will be administered (fasted) via IV for 4 days BID, followed by administration of GSK1322322 orally (fed) for 6 days BID. A follow-up evaluation will be conducted 7-10 days following last dose of for each subjects in each Part of the study.
Approximately 12 subjects will be enrolled in each part of the study such that approximately 8, 6, and 9 subjects complete dosing and critical assessments in part A,B, and C respectively.

开始日期2013-08-07

申办/合作机构

GSK Plc

100 项与 Lanopepden mesylate 相关的临床结果

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100 项与 Lanopepden mesylate 相关的转化医学

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100 项与 Lanopepden mesylate 相关的专利（医药）

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20

项与 Lanopepden mesylate 相关的文献（医药）

2018-03-01·Molecular informatics4区 · 医学

Virtual Screening Approach of Bacterial Peptide Deformylase Inhibitors Results in New Antibiotics

4区 · 医学

Article

作者: Okay, Sezer ; Chikhi, Abdelouahab ; Boucherit, Hanane ; Bensegueni, Abderrahmane ; Merzoug, Amina

Abstract:

The increasing resistance of bacteria to antibacterial therapy poses an enormous health problem, it renders the development of new antibacterial agents with novel mechanism of action an urgent need. Peptide deformylase, a metalloenzyme which catalytically removes N‐formyl group from N‐terminal methionine of newly synthesized polypeptides, is an important target in antibacterial drug discovery. In this study, we report the structure‐based virtual screening of ZINC database in order to discover potential hits as bacterial peptide deformylase enzyme inhibitors with more affinity as compared to GSK1322322, previously known inhibitor. After virtual screening, fifteen compounds of the top hits predicted were purchased and evaluated in vitro for their antibacterial activities against one Gram positive (Staphylococcus aureus) and three Gram negative (Escherichia coli, Pseudomonas aeruginosa and Klebsiella. pneumoniae) bacteria in different concentrations by disc diffusion method. Out of these, three compounds, ZINC00039650, ZINC03872971 and ZINC00126407, exhibited significant zone of inhibition. The results obtained were confirmed using the dilution method. Thus, these proposed compounds may aid the development of more efficient antibacterial agents.

2017-11-01·ANTIMICROBIAL AGENTS AND CHEMOTHERAPY

Reducing Antibacterial Development Risk for GSK1322322 by Exploring Potential Human Dose Regimens in Nonclinical Efficacy Studies Using Immunocompetent Rats.

Article

作者: DeMarsh, Peter ; Rittenhouse, Stephen ; Elefante, Philippa ; Singley, Christine M ; Hoover, Jennifer L ; Zalacain, Magdalena

Directly testing proposed clinical dosing regimens in nonclinical studies can reduce the risk during the development of novel antibacterial agents. Optimal dosing regimens can be identified in animal models by testing recreated human pharmacokinetic profiles. An example of this approach using continuous intravenous infusions of GSK1322322 in immunocompetent rats to evaluate recreated human exposures from phase I trials in pneumonia models with Streptococcus pneumoniae and Haemophilus influenzae and an abscess model with Staphylococcus aureus is presented. GSK1322322 was administered via continuous intravenous infusion to recreate 1,000- or 1,500-mg oral doses every 12 h in humans. Significant reductions (P ≤ 0.05 for all comparisons) in bacterial numbers compared with those for the baseline controls were observed for S. pneumoniae and H. influenzae (mean log₁₀ reductions, 1.6 to ≥2.7 and 1.8 to 3.3 CFU/lungs, respectively) with the recreated 1,000-mg oral dose. This profile was also efficacious against S. aureus (mean log₁₀ reduction, 1.9 to 2.4 CFU/abscess). There was a nonsignificant trend for improved efficacy against S. aureus with the 1,500-mg oral dose (mean log₁₀ reduction, 2.4 to 3.1 CFU/abscess). These results demonstrate that the human oral 1,000- or 1,500-mg exposure profiles of GSK1322322 recreated in rats were effective against representative community-associated pathogens and supported selection of the 1,500-mg oral dose given every 12 h for a phase II clinical skin infection study. Furthermore, this work exemplifies how the testing of recreated human pharmacokinetic profiles can be incorporated into the development process and serve as an aid for selecting optimal dosing regimens prior to conducting large-scale clinical studies.

2016-01-01·Antimicrobial agents and chemotherapy2区 · 医学

Pharmacokinetics/Pharmacodynamics of Peptide Deformylase Inhibitor GSK1322322 against Streptococcus pneumoniae, Haemophilus influenzae, and Staphylococcus aureus in Rodent Models of Infection

2区 · 医学

Article

作者: Novick, Steven J. ; Straub, Robert J. ; DeMarsh, Peter ; Aubart, Kelly ; Hoover, Jennifer ; Rittenhouse, Stephen ; Zalacain, Magdalena ; Lewandowski, Thomas

ABSTRACT:

GSK1322322 is a novel inhibitor of peptide deformylase (PDF) with goodin vitroactivity against bacteria associated with community-acquired pneumonia and skin infections. We have characterized thein vivopharmacodynamics (PD) of GSK1322322 in immunocompetent animal models of infection withStreptococcus pneumoniaeandHaemophilus influenzae(mouse lung model) and withStaphylococcus aureus(rat abscess model) and determined the pharmacokinetic (PK)/PD index that best correlates with efficacy and its magnitude. Oral PK studies with both models showed slightly higher-than-dose-proportional exposure, with 3-fold increases in area under the concentration-time curve (AUC) with doubling doses. GSK1322322 exhibited dose-dependentin vivoefficacy against multiple isolates ofS. pneumoniae,H. influenzae, andS. aureus. Dose fractionation studies with twoS. pneumoniaeandS. aureusisolates showed that therapeutic outcome correlated best with the free AUC/MIC (fAUC/MIC) index inS. pneumoniae(R2, 0.83), whereasfAUC/MIC and free maximum drug concentration (fCmax)/MIC were the best efficacy predictors forS. aureus(R2, 0.9 and 0.91, respectively). Median dailyfAUC/MIC values required for stasis and for a 1-log10reduction in bacterial burden were 8.1 and 14.4 for 11S. pneumoniaeisolates (R2, 0.62) and 7.2 and 13.0 for fiveH. influenzaeisolates (R2, 0.93). The data showed that for eightS. aureusisolates,fAUC correlated better with efficacy thanfAUC/MIC (R2, 0.91 and 0.76, respectively), as efficacious AUCs were similar for all isolates, independent of their GSK1322322 MIC (range, 0.5 to 4 μg/ml). MedianfAUCs of 2.1 and 6.3 μg · h/ml were associated with stasis and 1-log10reductions, respectively, forS. aureus.

100 项与 Lanopepden mesylate 相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D10713	-	-	DB11912

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
皮肤和皮肤结构感染	临床2期	美国	GSK Plc	2010-08-17
细菌性皮肤疾病	临床2期	美国	GSK Plc	2010-08-17
细菌感染	临床1期	澳大利亚	GSK Plc	2009-05-11

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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


NCT01209078 (CTgov)	临床2期	细菌性皮肤疾病 \| 皮肤和皮肤结构感染	84	GSK1322322 (GSK1322322 1500 mg BID)	夢鏇膚願膚衊願選構襯(製憲廠廠願蓋鏇築觸獵) = 淵憲選鹹鬱製醖餘構顧鏇鹽選選夢醖襯築夢鹹 (壓齋鑰構夢糧窪選餘窪, 範築簾醖觸鑰選選衊簾 ~ 構窪獵範選憲壓獵淵選) 更多	-	2017-12-04
				Linezolid (Linezolid 600 mg BID)	夢鏇膚願膚衊願選構襯(製憲廠廠願蓋鏇築觸獵) = 衊製壓淵餘衊網鏇顧廠鏇鹽選選夢醖襯築夢鹹 (壓齋鑰構夢糧窪選餘窪, 範網選餘襯網網範鏇膚 ~ 醖膚夢鑰觸願遞窪醖艱) 更多
NCT01209078 (Pubmed \| Antimicrob Agents Chemother)	临床2期	皮肤和皮肤结构感染	84	GSK1322322 1,500 mg b.i.d.	糧遞夢衊憲壓簾簾廠鏇(夢構蓋壓獵襯齋夢網齋) = mild-to-moderate drug-related adverse events, most commonly, diarrhea 鑰蓋蓋鏇鹽醖衊簾觸範 (鬱蓋衊壓簾艱憲窪範糧 ) 更多	-	2014-11-01
				Linezolid 600 mg b.i.d.
NCT01610388 (Pubmed \| Antimicrob Agents Chemother)	临床1期	细菌感染	61	GSK1322322	齋製鑰艱顧襯顧積鬱糧(範鬱鏇築鹹觸齋蓋餘鏇) = 憲餘製鏇積夢憲艱襯襯憲鬱衊壓構鏇窪鹹鹹壓 (襯遞網鏇鬱遞鹹窪積築 ) 更多	-	2014-01-01