尼莫唑(Nimorazole) - 在研适应症：阿米巴病，贾第虫病，牙龈炎_专利_临床

概要

基本信息

药物类型

小分子化药

别名

Nimoral、Nimorazole (INN)

+ [3]

靶点-

作用机制

DNA合成抑制剂

治疗领域

感染消化系统疾病口颌疾病

在研适应症

阿米巴病贾第虫病牙龈炎+ [1]

非在研适应症

局部晚期头颈部鳞状细胞癌

原研机构-

在研机构-

非在研机构

The Christie Pathology Partnership LLP

最高研发阶段批准上市

首次获批日期-

最高研发阶段(中国)-

特殊审评孤儿药 (欧盟)

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结构

分子式C9H14N4O3

InChIKeyMDJFHRLTPRPZLY-UHFFFAOYSA-N

CAS号6506-37-2

关联

8

项与尼莫唑相关的临床试验

CTRI/2019/02/017477 / Recruiting临床2期IIT

A Phase II trial of Nimorazole with chemoradiation as primary treatment for locally advanced cervical cancer compared to chemoradiation alone

开始日期2019-03-15

申办/合作机构-

NCT02661152 / Unknown status临床3期IIT

DAHANCA 30: A Randomized Non-inferiority Trial of Hypoxia-profile Guided Hypoxic Modification With Nimorazole During Radiotherapy/Chemoradiotherapy of Squamous Cell Carcinoma of the Head and Neck.

Hypoxic modification of radiotherapy with nimorazole has previously been shown to increase radiosensitivity in hypoxic head and neck squamous cell carcinomas (HNSCC).
In Denmark, nimorazole is added the radiotherapy of most HNSCC, as it has not previously been possible to discriminate more hypoxic tumours from less hypoxic tumours.
A hypoxia gene profile has shown to discriminate between responders and non-responders to nimorazole.
In DAHANCA 30, expected hypoxia profile guided non-responders are randomized to +/- nimorazole during radiotherapy.This in order to verify clinical use of the gene profile in selecting the relevant patients for hypoxic modification of radiotherapy with nimorazole.

开始日期2016-09-01

申办/合作机构

Danish Head And Neck Cancer Group

EUCTR2015-004133-27-DK / Unknown status临床3期IIT

A randomized non-inferiority trial of hypoxia-profile guided hypoxic modification with nimorazole during radiotherapy/chemoradiotherapy of squamous cell carcinoma of the head and neck

开始日期2016-04-18

申办/合作机构-

100 项与尼莫唑相关的临床结果

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100 项与尼莫唑相关的转化医学

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100 项与尼莫唑相关的专利（医药）

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137

项与尼莫唑相关的文献（医药）

2024-10-01·Radiotherapy and Oncology

Transcriptomic and epigenetic landscape of nimorazole-enhanced radiochemotherapy in head and neck cancer

Article

作者: Besso, María José ; Baumann, Michael ; Conde-Lopez, Cristina ; Wijaya Hadiwikarta, Wahyu ; Kurth, Ina ; Bitto, Verena ; Schneider, Karolin ; Bonrouhi, Mahnaz ; Euler-Lange, Rosemarie ; Krause, Mechthild ; Linge, Annett ; Koi, Lydia

BACKGROUNDHypoxia remains a challenge for the therapeutic management of head and neck squamous cell carcinoma (HNSCC). The combination of radiotherapy with nimorazole has shown treatment benefit in HNSCC, but the precise underlying molecular mechanisms remain unclear.PURPOSETo assess and to characterize the transcriptomic/epigenetic landscape of HNSCC tumor models showing differential therapeutic response to fractionated radiochemotherapy (RCTx) combined with nimorazole.MATERIALS/METHODSBulk RNA-sequencing and DNA methylation experiments were conducted using untreated and treated HNSCC xenografts after 10 fractions of RCTx with and without nimorazole. These tumor models (FaDu, SAS, Cal33, SAT and UT-SCC-45) previously showed a heterogeneous response to RCTx with nimorazole. The prognostic impact of candidate genes was assessed using clinical and gene expression data from HNSCC patients treated with primary RCTx within the DKTK-ROG.RESULTSNimorazole responder and non-responder tumor models showed no differences in hypoxia gene signatures However, non-responder models showed upregulation of metabolic pathways. From that, a subset of 15 differentially expressed genes stratified HNSCC patients into low and high-risk groups with distinct outcome.CONCLUSIONIn the present study, we found that nimorazole non-responder models were characterized by upregulation of genes involved in Retinol metabolism and xenobiotic metabolic process pathways, which might contribute to identify mechanisms of resistance to nitroimidazole compounds and potentially expand the repertoire of therapeutic options to treat HNSCC.

2024-07-01·International Journal of Radiation Oncology*Biology*Physics

Randomized Phase 3 Trial of the Hypoxia Modifier Nimorazole Added to Radiation Therapy With Benefit Assessed in Hypoxic Head and Neck Cancers Determined Using a Gene Signature (NIMRAD)

Article

作者: West, Catharine M ; Irlam, Joely ; Yang, Huiqi ; More, Elisabet ; Schipani, Stefano ; Bolton, Steve ; Mistry, Hitesh ; Melillo, Nicola ; Slevin, Nick J ; Sen, Mehmet ; Evans, Mererid ; Price, James M ; Nutting, Christopher ; Lee, Lip ; Baines, Helen ; Thomson, David J ; Garcez, Kate ; Betts, Guy

PURPOSETumor hypoxia is an adverse prognostic factor in head and neck squamous cell carcinoma (HNSCC). We assessed whether patients with hypoxic HNSCC benefited from the addition of nimorazole to definitive intensity modulated radiation therapy (IMRT).METHODS AND MATERIALSNIMRAD was a phase 3, multicenter, placebo-controlled, double-anonymized trial of patients with HNSCC unsuitable for concurrent platinum chemotherapy or cetuximab with definitive IMRT (NCT01950689). Patients were randomized 1:1 to receive IMRT (65 Gy in 30 fractions over 6 weeks) plus nimorazole (1.2 g/m² daily, before IMRT) or placebo. The primary endpoint was freedom from locoregional progression (FFLRP) in patients with hypoxic tumors, defined as greater than or equal to the median tumor hypoxia score of the first 50 patients analyzed (≥0.079), using a validated 26-gene signature. The planned sample size was 340 patients, allowing for signature generation in 85% and an assumed hazard ratio (HR) of 0.50 for nimorazole effectiveness in the hypoxic group and requiring 66 locoregional failures to have 80% power in a 2-tail log-rank test at the 5% significance level.RESULTSThree hundred thirty-eight patients were randomized by 19 centers in the United Kingdom from May 2014 to May 2019, with a median follow-up of 3.1 years (95% CI, 2.9-3.4). Hypoxia scores were available for 286 (85%). The median patient age was 73 years (range, 44-88; IQR, 70-76). There were 36 (25.9%) locoregional failures in the hypoxic group, in which nimorazole + IMRT did not improve FFLRP (adjusted HR, 0.72; 95% CI, 0.36-1.44; P = .35) or overall survival (adjusted HR, 0.96; 95% CI, 0.53-1.72; P = .88) compared with placebo + IMRT. Similarly, nimorazole + IMRT did not improve FFLRP or overall survival in the whole population. In total (N = 338), 73% of patients allocated nimorazole adhered to the drug for ≥50% of IMRT fractions. Nimorazole + IMRT caused more acute nausea compared with placebo + IMRT (Common Terminology Criteria for Adverse Events version 4.0 G1+2: 56.6% vs 42.4%, G3: 10.1% vs 5.3%, respectively; P < .05).CONCLUSIONSAddition of the hypoxia modifier nimorazole to IMRT for locally advanced HNSCC in older and less fit patients did not improve locoregional control or survival.

2024-07-01·Heliyon

Evaluating deposited radiation energy amount and collision quantities of small-molecule radiosensitizers through Monte Carlo simulations

Article

作者: Mesbahi, A ; Hamad, Mawieh ; Almansoori, Asma ; ALMisned, Ghada ; Tekin, H O ; Kilic, Ceyda Sibel

This study investigates the photon interaction mechanism of various small molecule radiosensitizers, including Hydrogen Peroxide, Nimorazole, 5-Fluorouracil, NVX-108, and others, using the MCNP 6.3 Monte Carlo simulation code. The simulations focused on quantifying the linear attenuation coefficients, mean free path, and accumulation factors of these radiosensitizers, as well as their interactions in a simulated spherical water phantom irradiated with a 100 keV mono-energetic X-ray source. Our findings reveal significant variations in deposited energy, collision events, and mean free path among the radiosensitizers, indicating different efficacy levels in enhancing radiation therapy. Notably, NVX-108 demonstrated the highest energy deposition, suggesting its potential as a highly effective radiosensitizer. The study also examined the individual attenuation properties of these radiosensitizers against energetic photons, with NVX-108 showing the highest attenuation coefficient and a shorter mean free path, further supporting its superior potential in effective radiosensitization. It can be concluded that NVX-108 has higher interaction tendency with the energetic photons comparing other small-molecules under investigation.

100 项与尼莫唑相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D07352	尼莫唑	P01AB06	DB12172

研发状态

批准上市

10 条最早获批的记录,

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适应症	国家/地区	公司	日期
阿米巴病	-	-	-
贾第虫病	-	-	-
牙龈炎	-	-	-
滴虫感染	-	-	-

未上市

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
局部晚期头颈部鳞状细胞癌	临床2期	英国	The Christie Pathology Partnership LLP	2014-09-11

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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


NCT01950689 (NIMRAD, ASCO2023) 人工标引	临床3期	头颈部肿瘤	139	Nimorazole+RT (hypoxic group)	簾憲選製鹹遞襯齋齋糧(衊鹽蓋鑰繭壓壓鹽選蓋): adjusted HR = 0.72 (95% CI, 0.36 ~ 1.44), P-Value = 0.35 更多	不佳	2023-05-31
				Placebo+RT (hypoxic group)