Anaerobic bacteria; protozoa (Trichomonas vaginalis, Giardia intestinalis); hypoxia-inducible factors. Nimorazole is a nitroimidazole anti-infective that acts against anaerobic microorganisms. Its mechanism of action involves reductive activation of the nitro group within susceptible organisms, leading to DNA damage and cell death. As a radiosensitizer, nimorazole targets hypoxic tumor cells, enhancing the effectiveness of radiotherapy by sensitizing hypoxic cells to ionizing radiation.

Nimorazole,a nitroimidazole anti-infective, is a hypoxic radiosensitizer potentially useful in the treatment of patients with head and neck squamous cell carcinoma (HNSCC). Nimorazole significantly improves the effect of radiotherapeutic management of supraglottic and pharynx tumors and can be given without major side-effects. Nimorazole is the only such chemical reagent that has shown a significant effect in a randomized controlled trial in head and neck cancer.

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In vitro, nimorazole is active against Trichomonas vaginalis with an EC₅₀ of 2.55 fmol/cell and against Giardia intestinalis with an IC₅₀ of 0.393 μM. The compound demonstrates antimicrobial activity against anaerobic bacteria. As a radiosensitizer, nimorazole enhances the sensitivity of hypoxic tumor cells to radiation in vitro. These activities support its use as an anti-infective and as a radiosensitizing agent in cancer therapy.

In vivo (clinical) activity: 61 patients with stage III/IV head and neck squamous cell carcinoma treated with CHART (56.75 Gy in 36 fractions over 12 days) plus nimorazole. Two‑year loco‑regional control was 55% overall (stage III 62%, stage IV 50%). Local control for T3 primary lesions was 77% and for T4 39%. Regional lymph node control at 2 years in node‑positive patients was 59%. Compared to historical CHART alone, results were higher (e.g., MRC trial CHART alone gave 40% for T3 and 31% for T4). [1]
Nimorazole has been used in clinical trials studying the treatment of head and neck squamous cell carcinoma, where it is evaluated as a hypoxic radiosensitizer. The compound enhances the effectiveness of radiotherapy in patients with hypoxic tumors. In vivo, nimorazole sensitizes hypoxic tumor cells to radiation, improving treatment outcomes. Clinical trials have investigated its role in hypoxic modification during radiotherapy.

The antimicrobial activity of nimorazole is typically assessed using standard susceptibility testing methods. For Trichomonas vaginalis, a Coulter counter antimicrobial assay is used to determine EC₅₀ values. For Giardia intestinalis, IC₅₀ values are determined using growth inhibition assays. For radiosensitizing activity, hypoxic cell cultures (e.g., tumor cell lines) are treated with nimorazole and exposed to radiation. Cell survival is assessed by colony formation or clonogenic assays to determine the sensitizer enhancement ratio.

Cells susceptible to nimorazole (e.g., anaerobic bacteria, protozoa, or tumor cell lines for radiosensitization studies) are cultured under appropriate conditions. For antimicrobial testing, microorganisms are incubated with varying concentrations of nimorazole, and growth inhibition is measured by optical density, colony counting, or other appropriate methods. For radiosensitization studies, tumor cells are cultured under hypoxic conditions, treated with nimorazole, and exposed to radiation. Cell survival is assessed by clonogenic assays.

Nimorazole has been evaluated in clinical trials for head and neck squamous cell carcinoma. In these trials, patients receive nimorazole as a radiosensitizer in combination with radiotherapy. The compound is typically administered orally at specific doses and schedules during the course of radiation treatment. Clinical endpoints include tumor response, local control, and survival. The compound's role in hypoxic modification has been studied in various clinical settings.

Pharmacokinetics: In a previous phase I dose‑escalation study (reference 1), the regimen of 1.2 g/m² (morning), 0.9 g/m² (midday), and 0.6 g/m² (evening) was shown to give plasma nimorazole concentrations consistently at or above 30 μg/mL at the time of irradiation. In five randomly selected patients from this study, mean plasma concentration was 47.9 μg/mL (range 34.9‑61.9 μg/mL) measured immediately before irradiation. [1]
Nimorazole has a molecular weight of 226.23 g/mol and a molecular formula of C₉H₁₄N₄O₃. It is soluble in DMSO at ≥70 mg/mL. The compound is well-absorbed after oral administration and achieves sufficient concentrations in tumor tissue for radiosensitization. Pharmacokinetic studies have been conducted to support its use in clinical trials. Nimorazole is metabolized primarily in the liver and excreted in urine.

Toxicity: Nearly all patients experienced some nausea. Grade 3 nausea occurred in 13 patients (22%) and grade 3 vomiting in 3 (5%). Vomiting was well controlled with cyclizine or metoclopramide. Two patients developed mild transient peripheral sensory neuropathy. One patient (aged 73, heavy drinker) developed encephalopathy during treatment – transient loss of consciousness, shaking episodes, confusion, slurred speech, unsteadiness; MRI showed atrophy, CSF normal, EEG slow normal; he died 10 days after stopping treatment. Autopsy revealed brain changes (chromatolysis, microvacuolation of white matter, reactive astrocytosis) consistent with nimorazole CNS toxicity interfering with mitochondrial function leading to cellular energy deprivation. No cirrhosis or alcohol‑related brain disease was found. This was considered an idiosyncratic reaction. Compliance was 95%. [1]
Detailed toxicology data for nimorazole are available from clinical studies. As a nitroimidazole compound, common adverse effects may include gastrointestinal disturbances, neurological effects, and hypersensitivity reactions. The compound has been evaluated for safety in clinical trials for head and neck cancer. Standard preclinical toxicology studies would have been conducted to support clinical development.

Radiother Oncol.2003 Jan;66(1):65-70.

Nimorazole belongs to the imidazole class of compounds and is a C-nitro compound. Nimorazole has been used in therapeutic trials for various diseases, including hypoxia, radiotherapy, hypoxia modification, genomic profiling, gene characterization, and head and neck squamous cell carcinoma. Nimorazole is a water-soluble 5-nitroimidazole compound with antibacterial and potential radiosensitizing activities. As an oxygen mimic, Nimorazole can induce the generation of free radicals and make hypoxic cells more sensitive to the cytotoxic effects of ionizing radiation. This inhibits DNA repair, thereby exacerbating DNA strand damage and ultimately leading to tumor cell death. Nimorazole's activity is lower than that of 2-nitroimidazole compounds misotronidazole and ethamidazole, but it is also less toxic. Nimorazole is an antitrichomonal drug, effective both topically and orally; its urinary metabolites also have trichomonadic activity.

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Nimorazole is a 5‑nitroimidazole compound, distinct from 2‑nitroimidazoles (misonidazole, etanidazole). It is very soluble, rapidly absorbed orally, diffuses readily into poorly vascularized tumours, and is not lipophilic, thus lacks cumulative neurotoxicity, allowing it to be given with each fraction. Its action is independent of fraction size and has a less steep dose‑response relationship compared to other sensitizers. In this study, nimorazole was given orally or enterally (tablets crushed via feeding tube) 90 min before radiotherapy. Doses were rounded to nearest 250 mg. The drug was supplied as 500 mg scored tablets. The regimen achieved plasma levels above 30 μg/mL consistently. No increase in late radiation effects was observed except possibly a slight increase in acute skin reaction (dry desquamation 47%, moist desquamation 15%). Mucositis severity and duration were similar to previous CHART studies. The combination showed promising local control rates compared to historical CHART alone. [1]
Nimorazole is a 5-nitroimidazole compound with antimicrobial and radiosensitizing activities. It is active against anaerobic bacteria and protozoa. Nimorazole has been used in clinical trials as a hypoxic radiosensitizer for head and neck squamous cell carcinoma. The compound enhances the effectiveness of radiotherapy by sensitizing hypoxic tumor cells to radiation. Nimorazole has a molecular formula of C₉H₁₄N₄O₃ and a molecular weight of 226.23 g/mol.

C9H14N4O3

226.23

226.106

C, 47.78; H, 6.24; N, 24.77; O, 21.22

6506-37-2

94107-55-8 (HCl);6506-37-2;

23009

Light yellow solid powder

1.4±0.1 g/cm3

443.0±35.0 °C at 760 mmHg

221.7±25.9 °C

0.0±1.1 mmHg at 25°C

1.637

-0.08

0

5

3

16

239

0

O1C([H])([H])C([H])([H])N(C([H])([H])C1([H])[H])C([H])([H])C([H])([H])N1C([H])=NC([H])=C1[N+](=O)[O-]

MDJFHRLTPRPZLY-UHFFFAOYSA-N

InChI=1S/C9H14N4O3/c14-13(15)9-7-10-8-12(9)2-1-11-3-5-16-6-4-11/h7-8H,1-6H2

4-[2-(5-nitroimidazol-1-yl)ethyl]morpholine

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO : 33.33 ~45 mg/mL ( 147.33 ~198.91 mM)

Solubility in Formulation 1: ≥ 2.08 mg/mL (9.19 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 2.08 mg/mL (9.19 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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Solubility in Formulation 3: ≥ 2.08 mg/mL (9.19 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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Solubility in Formulation 4: 10% DMSO+40% PEG300+5% Tween-80+45% Saline: ≥ 2.08 mg/mL (9.19 mM)

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 (Please use freshly prepared in vivo formulations for optimal results.)