Drug intelligence / Profile preview

methotrexate + mitoxantrone + thiotepa

Development stage
Unknown
Lead developer
Pfizer
Modality
Nucleic Acid-Directed Small Molecules → Small Molecules, Covalent Small Molecules → Small Molecules, Classical Binding Small Molecules → Small Molecules
Administration
Intravenous
01

Overview

This drug is a combination chemotherapy regimen consisting of methotrexate, mitoxantrone, and thiotepa. Each component is a small molecule antineoplastic agent with distinct mechanisms of action: - Methotrexate is an antimetabolite that inhibits dihydrofolate reductase, blocking DNA synthesis and cell replication. - Mitoxantrone is an anthracenedione that intercalates into DNA and inhibits topoisomerase II, leading to DNA strand breaks. - Thiotepa is an alkylating agent that crosslinks DNA strands, preventing cell division. The combination has been studied as the TMM regimen for metastatic breast cancer. In clinical trials, it was administered intravenously every three weeks. The main toxicity observed was myelosuppression. Partial responses were reported in some patients with metastatic breast cancer[1]. This combination may also be considered for other cancers where these agents are individually indicated.

Other names
TMM
02

Targets

DHFR (Dihydrofolate reductase)TOP2A (DNA topoisomerase II)DNA

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