预约演示
更新于：2025-01-11
Clofazimine
氯法齐明
更新于：2025-01-11
概要
基本信息
最高研发阶段批准上市 |
首次获批日期 美国 (1986-12-15), |
最高研发阶段(中国)批准上市 |
特殊审评快速通道 (美国)、孤儿药 (美国)、合格传染病产品 (美国)、孤儿药 (欧盟) |
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结构/序列
分子式C27H22Cl2N4 |
InChIKeyWDQPAMHFFCXSNU-UHFFFAOYSA-N |
CAS号2030-63-9 |
关联
58
项与 氯法齐明 相关的临床试验NCT06649721
Innovating Shorter, All- Oral, Precised Treatment Regimen for Rifampicin Resistant Tuberculosis：BDLL Chinese Cohort
NCT06418711
ICoN-1: A Randomized, Double-Blind, Placebo-Controlled Phase 3 Study of the Efficacy and Safety of Clofazimine Inhalation Suspension When Added to Guideline-Based Therapy in Participants With Nontuberculous Mycobacterial Infection
NCT06081361
A Multicenter, Randomized, Open-Label Study To Evaluate The Efficacy And Safety Of A Contezolid, Delamanid and Bedaquiline-Containing Short Regimen For The Treatment Of Rifampicin-Resistant Pulmonary Tuberculosis
100 项与 氯法齐明 相关的临床结果
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100 项与 氯法齐明 相关的转化医学
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100 项与 氯法齐明 相关的专利（医药）
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1,865
项与 氯法齐明 相关的文献（医药）2025-02-01EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS
Human milk improves the oral bioavailability of the poorly water-soluble drug clofazimine
Article
作者: Pham, Anna C ; Huang, Shouyuan ; Ponsonby-Thomas, Ellie ; Offersen, Simone Margaard ; Klein, Laura D ; Thymann, Thomas ; Salim, Malinda ; Boyd, Ben J
Clofazimine is an emerging drug for the treatment of cryptosporidiosis in infants. As a poorly water-soluble drug, the formulation of clofazimine in age-appropriate vehicles is challenging and often results in the use of off-label formulations. Milk-based vehicles such as human milk and bovine milk have been investigated as age-appropriate formulations and shown to increase the solubilisation of poorly water-soluble drugs via enhanced solubility in lipid digestion products in vitro. We hypothesised that administration of clofazimine within a milk-based vehicle would enhance bioavailability for infant patients. Towards this objective, suspensions of clofazimine in human and bovine milk were orally administered separately to piglets and rats and the subsequent plasma concentrations were compared to those after administration of an aqueous drug suspension. Initial investigations with a rodent model showed a significant increase (258%) in the oral bioavailability of clofazimine when administered with human milk. Similarly, the oral bioavailability of clofazimine was significantly higher when administered in both human (154%) and bovine milk (175%) using a neonatal piglet model, suggesting comparable enhancement in oral bioavailability could be achieved with human or bovine milk. These findings demonstrate the potential of human milk in particular to provide an effective administration vehicle for clofazimine administration to infants without the need for additional excipients.
2025-01-03JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY
SQ31f is a potent non-tuberculous mycobacteria antibiotic by specifically targeting the mycobacterial F-ATP synthase
Article
作者: Roquet-Banères, Françoise ; Grüber, Gerhard ; Kremer, Laurent ; Harikishore, Amaravadhi ; Daher, Wassim ; Sae-Lao, Patcharaporn ; Ragunathan, Priya ; Bates, Roderick W
Abstract:
Background:
Non-tuberculous mycobacteria (NTM) infection presents a growing global health problem and requires new antibiotics targeting enzymes that are essential for the pathogens under various metabolic conditions, with high target specificity, good solubility and with attractive combinatory potency.
Methods:
SQ31f was synthesized by a simplified synthesis protocol, and its effect on growth inhibition of fast- and slow-growing NTM and clinical isolates, whole-cell ATP depletion, ex vivo macrophages and its potency in combination with other antibiotics were evaluated. Molecular docking studies were employed to assess SQ31f’s binding mode.
Results:
We present- squaramide SQ31f as a novel anti-NTM inhibitor targeting the NTM F1FO-ATP synthase, essential for ATP formation, regulation of ATP homeostasis and proton motive force under multiple growth conditions. The potency of SQ31f in growth inhibition of fast- and slow-growing NTM and clinical isolates correlates with whole-cell ATP depletion, which is not caused by altered oxygen consumption. SQ31f’s high aqueous solubility enables binding to the waterfilled cytosolic proton half channel in the subunits a–c interface of the FO domain. As presented for the fast-growing Mycobacterium abscessus, the compound is active against intracellular-residing M. abscessus. Importantly, SQ31f shows an additive effect of the anti-M. abscessus drugs clofazimine, rifabutin or amikacin, and an attractive potentiation of linezolid, clarithromycin, or the oral pair tebipenem and avibactam.
Conclusions:
SQ31f represents an attractive inhibitor to tackle the issues associated with NTM drug tolerance and toxicity. Its combinatory potency with anti-M. abscessus drugs holds potential for overcoming resistance, while also reducing intensive compound synthesis and associated costs.
2025-01-03JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY
In vitro monitoring of drug resistance emergence during stepwise induction of bedaquiline and clofazimine, alone and in combination: a phenotypic and genotypic analysis
Article
作者: Jiang, Guanglu ; Zhao, Liping ; Huang, Hairong ; Zheng, Jifang ; Shang, Yuanyuan ; Chen, Suting ; Chu, Naihui ; Huo, Fengmin ; Xue, Yi
Abstract:
Objectives:
The co-resistance between bedaquiline and clofazimine raises significant concerns, as they are commonly co-administered as core drugs in drug-resistant TB regimens. The present study aimed to monitor drug resistance-associated gene mutations and the phenotypic change in Mycobacterium tuberculosis (Mtb) under a stepwise drug resistance induction in vitro using bedaquiline, clofazimine or combined drugs.
Methods:
Drug-resistant Mtb strains were gradually induced in vitro on a drug-containing solid medium with a 2-fold increasing concentration of bedaquiline, clofazimine and their combination. The MIC of the induced drug-resistant Mtb strains was determined. The drug resistance-associated genes, including Rv0678, Rv1979c, atpE and pepQ, were sequenced and analysed.
Results:
Unlike exposure to bedaquiline alone or the combination of these two drugs, clofazimine alone resulted in drug resistance gene mutations occurring later, specifically in the fourth round of induction as opposed to the second round of induction. Besides, nucleotide deletion or insertion in Rv0678 was the main mutation type for induction under the two-drug combination, while single-nucleotide polymorphisms (SNPs) in Rv0678 were the major mutation types when induced by bedaquiline or clofazimine alone. Rv0678 mutation happened at a relatively lower bedaquiline concentration exposure alone, while atpE mutation occurred at a higher bedaquiline concentration. Regardless of the drug exposure manner, a strong correlation between bedaquiline MICs and clofazimine MICs was observed in all drug resistance strains.
Conclusions:
Combined exposure to bedaquiline and clofazimine developed Rv0678 mutation as early as exposure to bedaquiline alone. However, rather than SNPs, deletion and insertion were the dominant mutation types in dual-drug exposure strain.
100 项与 氯法齐明 相关的药物交易
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研发状态
批准上市
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| 适应症 | 国家/地区 | 公司 | 日期 |
|---|---|---|---|
| 麻风 | 美国 | 1986-12-15 |
未上市
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| 适应症 | 最高研发状态 | 国家/地区 | 公司 | 日期 |
|---|---|---|---|---|
| 非结核分枝杆菌感染 | 临床3期 | 美国 | 2024-09-11 | |
| 肺部疾病 | 临床申请批准 | 日本 | - |
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临床结果
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适应症
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临床2/3期 | 552 | rifampicin (Standard care) | 襯鏇膚淵簾衊襯製網憲(積壓窪淵鑰獵選簾築顧) = 鹹簾鬱構膚艱窪網憲廠 壓齋鏇艱鑰襯遞鹹鏇窪 (範繭窪艱齋獵願蓋製憲 ) 更多 | 积极 | 2024-02-01 | ||
(BPaLM) | 襯鏇膚淵簾衊襯製網憲(積壓窪淵鑰獵選簾築顧) = 築鹹壓鹹醖淵範製獵範 壓齋鏇艱鑰襯遞鹹鏇窪 (範繭窪艱齋獵願蓋製憲 ) 更多 | ||||||
临床4期 | 93 | Short-course regimen | 願襯築鹽築鏇願壓顧衊(窪積蓋憲鹹鑰積繭製築) = 16/17 醖簾顧繭製鏇願鑰醖構 (觸遞觸膚壓齋蓋網襯襯 ) | - | 2023-03-06 | ||
Standard regimen | |||||||
N/A | - | 齋簾膚夢鏇鹹窪繭繭壓(範獵衊獵襯積淵醖簾構) = 鑰鹹鏇襯襯觸鏇膚鬱蓋 觸積網蓋築艱築膚願鹽 (衊艱糧鬱齋餘觸衊鏇願 ) 更多 | - | 2022-05-15 | |||
临床2期 | - | 願願構繭範夢網夢糧夢(艱窪艱夢繭繭餘襯簾鹹) = The most frequent solicited adverse effects were diarrhea, abdominal pain, and malaise. 衊構憲鏇醖夢夢顧顧夢 (襯簾襯繭鹹齋夢艱襯網 ) 更多 | 不佳 | 2021-07-15 | |||
Placebo | |||||||
N/A | 105 | Cfz therapy group | 醖鹹構遞醖積構艱簾膚(觸積鹹鏇夢鑰鹹窪鏇構) = 47.2% 膚範夢鬱繭鑰網衊網積 (獵蓋築鑰鬱製餘鹽構網 ) 更多 | 积极 | 2015-09-01 | ||
N/A | 32 | 獵範膚顧廠鑰蓋壓構夢(築艱艱獵窪鏇獵鹹艱構) = Skin discoloration occurred in all patients and nine patients stopped clofazimine treatment due to adverse effects: skin discolorization(n=3), liver toxicity(n=3), and gastrointestinal disturbance(n=3) 憲衊鹽顧醖餘鹽繭餘繭 (願廠鏇窪夢構鹹醖糧構 ) | 不佳 | 2013-09-01 | |||
N/A | 92 | Clofazimine therapy | 製網淵糧遞築淵築築糧(構鑰醖選鏇鹽夢獵廠願) = ichthyosis occurred in 40 patients of clofazimine therapy group 繭膚鬱艱選艱網築衊製 (廠襯願夢範遞艱範壓鹽 ) 更多 | 积极 | 2013-09-01 | ||
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