Fexinidazole (HOE 239)
(Synonyms: 非昔硝唑; HOE 239) 目录号 : GC32094
An antiparasitic agent
Cas No.:59729-37-2
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Fexinidazole is an antiparasitic agent.1 It is active against 15 strains of T. brucei, including T. b. rhodesiense, T. b. brucei, and T. b. gambiense (IC50s = 0.95-3.31 ?M). Fexinidazole inhibits the growth of L. donovani at the promastigote and axenic amastigote stages (EC50s = 5.6 and 2.8 ?M, respectively).2 Fexinidazole (50 to 30 mg/kg per day) reduces parasitic burden and increases survival in a mouse model of infection with benznidazole-susceptible, -partially resistant, or -resistant T. cruzi.3 Formulations containing fexinidazole have been used in the treatment of African sleeping sickness and Chagas disease.
1.Su, L., Pan, P., Yan, P., et al.Role of vimentin in modulating immune cell apoptosis and infammatory responses in sepsisSci. Rep.9(1)5747(2019) 2.Wyllie, S.G., Patterson, S., Stojanovski, L., et al.The anti-trypanosome drug fexinidazole shows potential for treating visceral leishmaniasisSci. Transl. Med.4(119)119re111(2012) 3.Bahia, M.T., de Andrade, I.M., Martins, T.A.F., et al.Fexinidazole: A potential new drug candidate for Chagas diseasePLoS Negl. Trop. Dis.6(11)e1870(2012)
| Cas No. | 59729-37-2 | SDF | |
| 别名 | 非昔硝唑; HOE 239 | ||
| Canonical SMILES | O=[N+](C1=CN=C(COC2=CC=C(SC)C=C2)N1C)[O-] | ||
| 分子式 | C12H13N3O3S | 分子量 | 279.31 |
| 溶解度 | DMSO : 50 mg/mL (179.01 mM);Water : < 0.1 mg/mL (insoluble) | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 3.5803 mL | 17.9013 mL | 35.8025 mL |
| 5 mM | 0.7161 mL | 3.5803 mL | 7.1605 mL |
| 10 mM | 0.358 mL | 1.7901 mL | 3.5803 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
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| % DMSO % % Tween 80 % saline | ||||||||||
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计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
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Fexinidazole: First Global Approval
Drugs 2019 Feb;79(2):215-220.PMID:30635838DOI:10.1007/s40265-019-1051-6.
Fexinidazole Winthrop (hereafter referred to as Fexinidazole) is a DNA synthesis inhibitor developed by the Drugs for Neglected Diseases initiative (DNDi), in collaboration with Sanofi, for the oral treatment of human African trypanosomiasis (HAT) [commonly known as 'sleeping sickness'] and Chagas' disease. The drug is a 5-nitroimidazole derivative first discovered by Hoechst AG (now part of Sanofi) and was identified by the DNDi in 2005 as having activity against Trypanosoma brucei gambiense and T. b. rhodesiense. Under Article 58 of Regulation (EC) no. 726/2004 (a regulatory mechanism for reviewing new medicines destined for use outside of the EU), Fexinidazole has been granted a positive opinion by the EMA for the treatment of both the first-stage (haemo-lymphatic) and second-stage (meningo-encephalitic) of HAT due to T. b. gambiense (g-HAT) in adults and children aged ≿6 years and weighing ≿20 kg. This approval will facilitate and support marketing authorization application in endemic countries in 2019; following registration, Fexinidazole will be distributed via the WHO to endemic countries for g-HAT. Phase 3 evaluation of Fexinidazole for g-HAT is ongoing in the Democratic Republic of the Congo and Guinea and the drug is also in development for Chagas' disease, with a study currently ongoing in Spain. Clinical development for visceral leishmaniasis is discontinued. This article summarizes the milestones in the development of Fexinidazole leading to this first approval for g-HAT.
The activity of Fexinidazole (HOE 239) against experimental infections with Trypanosoma cruzi, trichomonads and Entamoeba histolytica
Ann Trop Med Parasitol 1983 Feb;77(1):13-26.PMID:6411009DOI:10.1080/00034983.1983.11811668.
A new 5-nitroimidazole compound, 1-methyl-2-(4-methylthiophenoxymethyl)-5-nitroimidazole: fexinidazole, HOE 239, was found to be highly active against experimental infections with Trypanosoma cruzi, Tritrichomonas foetus, Trichomonas vaginalis and Entamoeba histolytica. It was slightly superior to benznidazole and nifurtimox in suppressing parasitaemia in mice infected with T. cruzi. It also eradicated the parasites from infected mice after a prolonged treatment period. The order of activity of some standard 5-nitroimidazoles obtained on the basis of several mouse or hamster infections with trichomonads and E. histolytica, respectively, was: fexinidazole greater than tinidazole and ornidazole greater than metronidazole greater than nitrimidazine (nimorazole), except that ornidazole had an amoebicidal effect close to that of fexinidazole. The principal metabolites, the sulphoxide and the sulphone were as active as the parent compound against T. cruzi, trichomonads and E. histolytica infections in mice and hamsters, respectively. The general tolerability of fexinidazole in rodents, rabbits and dogs is good and there is a wide range between the effective and maximum tolerated dose. Some side effects, such as anaemia and reduction of body weight occurred in rats and dogs at high dose levels following prolonged administration (90-day test). Structure-activity relationships of various 5-nitroimidazoles substituted in the 2-position, pharmacokinetic properties and metabolism of the experimental compound, as well as its foetal and perinatal tolerance, are discussed.
Fexinidazole for Human African Trypanosomiasis, the Fruit of a Successful Public-Private Partnership
Diseases 2022 Oct 17;10(4):90.PMID:36278589DOI:10.3390/diseases10040090.
After 100 years of chemotherapy with impractical and toxic drugs, an oral cure for human African trypanosomiasis (HAT) is available: Fexinidazole. In this case, we review the history of drug discovery for HAT with special emphasis on the discovery, pre-clinical development, and operational challenges of the clinical trials of Fexinidazole. The screening of the Drugs for Neglected Diseases initiative (DNDi) HAT-library by the Swiss TPH had singled out Fexinidazole, originally developed by Hoechst (now Sanofi), as the most promising of a series of over 800 nitroimidazoles and related molecules. In cell culture, Fexinidazole has an IC50 of around 1 µM against Trypanosoma brucei and is more than 100-fold less toxic to mammalian cells. In the mouse model, Fexinidazole cures both the first, haemolymphatic, and the second, meningoencephalitic stage of the infection, the latter at 100 mg/kg twice daily for 5 days. In patients, the clinical trials managed by DNDi and supported by Swiss TPH mainly conducted in the Democratic Republic of the Congo demonstrated that oral Fexinidazole is safe and effective for use against first- and early second-stage sleeping sickness. Based on the positive opinion issued by the European Medicines Agency in 2018, the WHO has released new interim guidelines for the treatment of HAT including Fexinidazole as the new therapy for first-stage and non-severe second-stage sleeping sickness caused by Trypanosoma brucei gambiense (gHAT). This greatly facilitates the diagnosis and treatment algorithm for gHAT, increasing the attainable coverage and paving the way towards the envisaged goal of zero transmission by 2030.
The use of the 2 substituted 5-nitroimidazole, Fexinidazole (HOE 239) in the treatment of chronic T. brucei infections in mice
Z Parasitenkd 1983;69(5):577-81.PMID:6636983DOI:10.1007/BF00926669.
Relapse of chronic T. brucei infections was completely prevented by treating with either diminazene aceturate (Berenil) at 40 mg/kg or suramin (Germanin) at 20 mg/kg followed by four doses of the 2-substituted 5-nitroimidazole (Fexinidazole) (Hoe 239). None of these drugs administered singly elicited 100% permanent cures although a high percentage of the mice were cured with four doses of Fexinidazole at 250 mg/kg. A single dose of 20 mg/kg suramin followed by four daily doses of 30 mg/kg Fexinidazole will effectively eliminate all the trypanosomes from the brains of chronically infected mice.
Fexinidazole for the treatment of human African trypanosomiasis
Drugs Today (Barc) 2019 Nov;55(11):705-712.PMID:31840685DOI:10.1358/dot.2019.55.11.3068795.
On November 15, 2018, Fexinidazole Winthrop received a positive opinion from the European Medicines Agency (EMA) (under Article 58) for treatment of first-stage (hemolymphatic) and second-stage (meningoencephalitic) human African trypanosomiasis caused by Trypanosoma gambiense (gHAT) in adults and children 6 years and older and weighing 20 or more kg. This is the first oral regimen for gHAT that is effective in treating both disease stages. Although Fexinidazole has potential to simplify current therapies, it does not entirely eliminate the need for disease staging by lumbar puncture because patients with severe stage 2 disease (CSF WBC [cerebrospinal fluid white blood cells] greater than 100 cells/µL) should only be treated with Fexinidazole if no other suitable treatment is available. Nausea and vomiting are a common side effect and the drug must be administered during or after the patient's main meal under direct observation by trained health personnel. Due to late relapses, the EMA recommends follow-up to 24 months after treatment.