JNJ-38877618(JNJ-38877618) - 药物靶点：c-Met_在研适应症：肿瘤_专利_临床

概要

基本信息

药物类型

小分子化药

别名

+ [1]

靶点

c-Met

作用机制

c-Met抑制剂(肝细胞生长因子受体抑制剂)

治疗领域

肿瘤

在研适应症

肿瘤

非在研适应症-

原研机构

Johnson & Johnson

在研机构

Johnson & Johnson

DeuterOncology SA初创企业

非在研机构

Janssen-Cilag GmbH

OCTIMET Oncology NV初创企业

最高研发阶段临床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C20H12F2N6

InChIKeyKOAWAWHSMVKCON-UHFFFAOYSA-N

CAS号943540-74-7

关联

2

项与 JNJ-38877618 相关的临床试验

NCT03138083 / Terminated临床1/2期

A Modular, Multi-arm, Multi-part, First Time in Patient Study to Evaluate the Safety and Tolerability of OMO-1, Alone and in Combination With Anti-cancer Treatments, in Patients With Locally Advanced, Unresectable or Metastatic Solid Malignancies

This is a modular, first time in patient, open-label, multicentre study of OMO-1, administered orally, alone and in combination with anti-cancer treatments, in patients with locally advanced, unresectable or metastatic solid malignancies.

开始日期2017-08-08

申办/合作机构

OCTIMET Oncology NV初创企业

NCT01964872 / Completed临床1期

A Double Blind, Placebo-Controlled, Randomized, Single and Multiple Ascending Dose Study to Investigate the Safety, Tolerability, and Pharmacokinetics of JNJ-38877618 in Healthy Male Subjects

The purpose of the study is to assess the safety, tolerability, pharmacokinetics, and pharmacodynamic effects of single oral doses and multiple oral doses of JNJ-38877618 administered for 7 consecutive days in healthy adult male participants.

开始日期2013-11-01

申办/合作机构

Janssen-Cilag GmbH

100 项与 JNJ-38877618 相关的临床结果

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100 项与 JNJ-38877618 相关的转化医学

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100 项与 JNJ-38877618 相关的专利（医药）

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16

项与 JNJ-38877618 相关的文献（医药）

2023-12-11·The Oncologist

A Phase I Trial of the Dual MET Kinase/OCT-2 Inhibitor OMO-1 in Metastatic Solid Malignancies Including MET Exon 14 Mutated Lung Cancer

Article

作者: Jansen, Ellen ; Angevin, Eric ; Lolkema, Martijn P ; Krebs, Matthew G ; Pruis, Melinda A ; Prenen, Hans ; Forster, Martin D ; De Vos, Filip ; Perera, Timothy ; Plummer, Ruth ; Tjwa, Marc ; Van der Aa, Annegret ; Clack, Glen

AbstractIntroductionTargeted therapy in non-small cell lung cancer (NSCLC) patients with mesenchymal epithelial transition (MET) exon 14 skipping mutations (METex14) and MET amplifications has improved patients’ outcomes. The development of more potent MET kinase inhibitors could further benefit these patients. The aim of this trial is to determine the safety and recommended phase 2 dose (RP2D) of OMO-1 (an oral dual MET kinase/OCT-2 inhibitor) and to assess preliminary clinical efficacy in METex14-positive NSCLC and other MET-positive solid tumors.Materials and MethodsThis was a first-in-patient, open-label, multicenter study of OMO-1 in patients with locally advanced or metastatic solid malignancies. A standard 3 + 3 dose escalation design was utilized starting at a dose level of 100 mg BID continuously. Preliminary efficacy was investigated in patients with METex14-positive NSCLC, and MET amplified NSCLC and other solid tumors (MET basket).ResultsIn the dose-escalation part, 24 patients were included in 5 dose levels ranging from 100 mg twice daily (BID) to 400 mg BID. Most common adverse events (≥ 20%) were nausea, fatigue, vomiting, increased blood creatinine, and headache. The RP2D was determined at 250 mg BID. In the expansion cohorts, 15 patients were included (10 in METex14-positive NSCLC cohort and 5 in MET basket cohort) and received either 200 or 250 mg BID. Eight out of the 10 patients with METex14 positive NSCLC had stable disease as the best response.ConclusionOMO-1 was tolerated at the dose of 250 mg BID and shows initial signs of MET inhibition and anti-tumor activity in METex14 mutated NSCLC patients.

2019-01-01·Cell Chemical Biology1区 · 生物学

The Anti-amyloid Compound DO1 Decreases Plaque Pathology and Neuroinflammation-Related Expression Changes in 5xFAD Transgenic Mice

1区 · 生物学

Article

作者: Meier, Jochen C ; Vannoni, Elisabetta ; Wiglenda, Thomas ; Diez, Lisa ; Babila, Julius T ; Martens, Henrik ; Loos, Maarten ; Beule, Dieter ; Andrade-Navarro, Miguel A ; Erck, Christian ; Groenke, Nicole ; Haenig, Christian ; Schnoegl, Sigrid ; Wolfer, David P ; Wanker, Erich E ; Neuendorf, Nancy ; Huska, Matthew R ; Nietfeld, Wilfried ; Boeddrich, Annett ; Friedrich, Beate ; Buntru, Alexander ; Blanc, Eric ; Jacob, Manuela

Self-propagating amyloid-β (Aβ) aggregates or seeds possibly drive pathogenesis of Alzheimer's disease (AD). Small molecules targeting such structures might act therapeutically in vivo. Here, a fluorescence polarization assay was established that enables the detection of compound effects on both seeded and spontaneous Aβ42 aggregation. In a focused screen of anti-amyloid compounds, we identified Disperse Orange 1 (DO1) ([4-((4-nitrophenyl)diazenyl)-N-phenylaniline]), a small molecule that potently delays both seeded and non-seeded Aβ42 polymerization at substoichiometric concentrations. Mechanistic studies revealed that DO1 disrupts preformed fibrillar assemblies of synthetic Aβ42 peptides and decreases the seeding activity of Aβ aggregates from brain extracts of AD transgenic mice. DO1 also reduced the size and abundance of diffuse Aβ plaques and decreased neuroinflammation-related gene expression changes in brains of 5xFAD transgenic mice. Finally, improved nesting behavior was observed upon treatment with the compound. Together, our evidence supports targeting of self-propagating Aβ structures with small molecules as a valid therapeutic strategy.

2012-09-01·Contact Dermatitis2区 · 医学

Patch testing with the textile dyes Disperse Orange 1 and Disperse Yellow 3 and some of their potential metabolites, and simultaneous reactions to para‐amino compounds

2区 · 医学

Article

作者: Magnus Bruze ; Laura Malinauskiene ; Kristina Ryberg ; Erik Zimerson ; Marlene Isaksson

Background. It is known that, in vitro, human skin bacteria are able to split disperse azo dyes into the corresponding aromatic amines, some of which are sensitizers in the local lymph node assay. We hypothesize that the molecules of disperse dyes migrate onto the skin while garments are worn, and are metabolized and degraded by commensal skin bacteria. These molecules penetrate the skin and induce sensitization.Objectives. To evaluate the elicitation capacities of the possible azo‐degradation products of the selected azo disperse dyes in patients allergic to them and to compare it with the elicitation capacities of other para‐compunds.Methods. Ten patients allergic to Disperse Yellow 3 (DY3) and/or Disperse Orange 1 (DO1) were patch tested with a dilution series of the purified dyes 4‐nitroaniline and p‐aminodiphenylamine in concentrations equimolar to those of purified DO1 in the dilution series, as well as 4‐aminoacetanilide and 2‐amino‐p‐cresol in concentrations equimolar to those of purified DY3 in the dilution series.Results. Three patterns of patch test reactions could be seen. The 6 patients who were positive to DO1 and DY3 also reacted to p‐aminodiphenylamine and 2‐amino‐p‐cresol. Two patients were positive to DO1 only, and both reacted to p‐aminodiphenylamine, but to neither 4‐aminoacetanilide or 2‐amino‐p‐cresol. Two patients did not react to DO1 or DY3 on this occasion.Conclusion. We show that it is possible that the major sensitizers in contact allergy to DO1 and DY3 are their metabolites, p‐aminodiphenylamine and 2‐amino‐p‐cresol, respectively, which might be formed by the azoreductase pathway of skin bacteria.

100 项与 JNJ-38877618 相关的药物交易

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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
肿瘤	临床2期	-	Johnson & Johnson	-

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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


NCT03138083 (ASCO2019) 人工标引	临床1/2期	晚期癌症 MET Mutation \| MET Amplification	34	JNJ-38877618 (Module 1)	(製繭衊壓糧構製網醖鹹) = 36 SAEs：17 in 11 subjects were considered related to OMO-1, and included nausea (3/17), vomiting (4/17), chills, diarrhoea, influenza-like illness (2/17), increased blood bilirubin, blood creatinine (3/17) and neutrophil count, and sepsis 鏇願獵窪觸蓋積鏇壓鹹 (壓鹽憲淵夢遞齋鏇餘憲 ) 更多	积极	2019-06-01