Temozolomide

Temozolomide is an oral alkylating agent and antineoplastic drug approved for the treatment of glioblastoma multiforme and anaplastic astrocytoma. As a DNA-methylating prodrug, Temozolomide undergoes rapid chemical conversion in the systemic circulation at physiological pH to the active compound MTIC, which covalently interacts with guanine residues in DNA. Temozolomide induces apoptosis and causes cell cycle arrest at the G2/M checkpoint. Temozolomide is supplied as a crystalline solid and is available as both an API for pharmaceutical manufacturing and as an analytical reference standard. For pharmaceutical quality control and analytical development, Temozolomide serves as an essential reference standard for impurity profiling, method validation, and stability studies.

 

Product Parameters

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Parameter	Specification
Product Name	Temozolomide
CAS Number	85622-93-1
Molecular Formula	C₆H₆N₆O₂
Molecular Weight	194.15 g/mol
Appearance	White to light brown powder
Melting Point	212 °C (dec.)
Boiling Point	526.6±42.0℃
Density	1.97±0.1 g/cm3
Storage Condition	2–8 °C

Antitumor D rug

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      Temozolomide is the first orally effective imidazotetrazine-class antitumor agent and belongs to the second generation of alkylating agents with antitumor activity. It does not require hepatic metabolic activation after oral administration, exhibits excellent permeability across the blood-brain barrier, demonstrates good tolerability without cumulative toxicity with other drugs, and demonstrates synergistic efficacy with radiotherapy. It is indicated for recurrent malignant gliomas following conventional treatment, such as glioblastoma multiforme or degenerative astrocytoma, and serves as a first-line treatment for metastatic melanoma.

 

Temozolomide was synthesized by the UK Cancer Research Group and subsequently transferred to Schering-Plough in the United States for development. Unlike existing antitumor drugs, this agent possesses a novel chemical structure as an imidazolotetrazine derivative. Temozolomide does not act directly; under physiological pH conditions, it rapidly converts via a non-enzymatic pathway into the active compound MTIC [5-(3-methyltriazepin-1)-imidazole-4-amide]. The cytotoxicity of MTIC is primarily attributed to its DNA alkylating (methylation) effect, which predominantly occurs at the O6 and N7 positions of guanine. Basic and clinical studies have demonstrated that temozolomide is effective against several common types of gliomas. It was approved for marketing in both the European Union and the United States in 1999: in the US, it was indicated for second-line treatment of glioblastoma multiforme and degenerative astrocytoma, while in EU countries, it was approved for glioblastoma multiforme with disease progression or recurrence after conventional therapy. The efficacy of temozolomide against glioblastoma multiforme has gained broader recognition in Europe.

 

 Pharmacokinetics

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This drug is completely absorbed orally with a bioavailability of nearly 100%, demonstrating broad-spectrum activity in murine tumor models and crossing the human blood-brain barrier. The cytotoxic effect of temozolomide stems from its potent methylation of DNA bases. Under alkaline conditions, temozolomide rapidly cleaves to form active methyl azide ions. Due to the higher alkalinity of brain tumors compared to surrounding tissues, drug activation occurs predominantly at the tumor site, resulting in strong antitumor efficacy with selective action. This also leads to improved side-effect profiles, reduced bone marrow toxicity, and enhanced patient tolerance.

 

 

Clinical E valuation

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      Temozolomide is effective in the treatment of newly diagnosed glioblastomas multiformes. Results from a small Phase II trial demonstrated that among 33 patients treated with temozolomide (200 mg/m²), 17 achieved complete or partial remission, while another 4 exhibited stable disease progression. The average time from remission to disease progression was 7 months in the 17 remitted patients compared to 2 months in those who did not respond to therapy; their mean survival periods were 12 months and 6 months, respectively. However, the efficacy of temozolomide in newly diagnosed degenerative astrocytomas remains unclear.

 

Temozolomide demonstrates significant efficacy against gliomas, particularly the most common type, glioblastoma multiforme, whether in terms of tumor response rate, patient survival rate, or tolerability. More importantly, it markedly improves patients' quality of life compared to the current standard treatment, procarbazine, representing a promising advancement in the management of this malignancy. The role of temozolomide as first-line therapy for progressive metastatic melanoma has been validated by clinical trials, with applications submitted in Europe and the United States. A recently published Phase III randomized controlled trial revealed that among 305 patients treated with temozolomide (200 mg/m²) combined with dacarbazine (250 mg/m² daily for 5 consecutive days every 21 days), the overall survival time and treatment response rate in the temozolomide group were 7.9 months and 13.5%, respectively, superior to those of the dacarbazine group (5.7 months and 12.1%). Temozolomide also exhibited better tolerability than dacarbazine, with significantly improved quality-of-life assessments measured by functional decline rates (18% vs. 42% after 3 months of treatment). Melanoma is a rare cutaneous tumor accounting for only approximately 4% of all skin cancers but contributing to about 79% of mortality cases; dacarbazine remains the current standard treatment for this condition. Temozolomide has demonstrated remarkable clinical efficacy in refractory gliomas and melanomas, warranting further attention.

 

Contact Us

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Need Temozolomide for your oncology API manufacturing campaign, impurity profiling program, or DNA alkylation research? Cosperpharm is your trusted partner. Contact our team today for pricing, documentation, or technical support—we'll respond promptly to your inquiry.