Repositioning Candidate Details
| Candidate ID: | R0430 |
| Source ID: | DB01157 |
| Source Type: | approved; investigational |
| Compound Type: | small molecule |
| Compound Name: | Trimetrexate |
| Synonyms: | Trimetrexate |
| Molecular Formula: | C19H23N5O3 |
| SMILES: | COC1=CC(NCC2=C(C)C3=C(C=C2)N=C(N)N=C3N)=CC(OC)=C1OC |
| Structure: |
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| DrugBank Description: | A nonclassical folic acid inhibitor through its inhibition of the enzyme dihydrofolate reductase. It is being tested for efficacy as an antineoplastic agent and as an antiparasitic agent against pneumocystis pneumonia in AIDS patients. Myelosuppression is its dose-limiting toxic effect. |
| CAS Number: | 52128-35-5 |
| Molecular Weight: | 369.4176 |
| DrugBank Indication: | For use, with concurrent leucovorin administration (leucovorin protection), as an alternative therapy for the treatment of moderate-to-severe <i>Pneumocystis carinii</i> pneumonia (PCP) in immunocompromised patients, including patients with the acquired immunodeficiency syndrome (AIDS). Also used to treat several types of cancer including colon cancer. |
| DrugBank Pharmacology: | Trimetrexate, a non-classical folate antagonist, is a synthetic inhibitor of the enzyme dihydrofolate reductase (DHFR). During DNA synthesis and cellular reproduction, folic acid is reduced to tetrahydrofolic acid by the enzyme folic acid reductase. By interfering with the reduction of folic acid, trimetrexate interferes with tissue cell reproduction. Generally, the most sensitive cells to the antimetabolite effect of trimetrexate are those cells which are most actively proliferating such as malignant cells, dermal epithelium, buccal and intestinal mucosa, bone marrow, fetal cells, and cells of the urinary bladder. Because the proliferation of cells in malignant tissues is greater than in most normal tissues, trimetrexate may impair the growth of the malignant tissues without causing irreversible damage to normal tissues. Due to very serious and potentially life-threatening side-effects of this drug, leucovorin must be co-administered for at least 72 hours after the last dose. |
| DrugBank MoA: | In vitro studies have shown that trimetrexate is a competitive inhibitor of dihydrofolate reductase (DHFR) from bacterial, protozoan, and mammalian sources. DHFR catalyzes the reduction of intracellular dihydrofolate to the active coenzyme tetrahydrofolate. Inhibition of DHFR results in the depletion of this coenzyme, leading directly to interference with thymidylate biosynthesis, as well as inhibition of folate-dependent formyltransferases, and indirectly to inhibition of p.r.n. biosynthesis. The end result is disruption of DNA, RNA, and protein synthesis, with consequent cell death. |
| Targets: | Dihydrofolate reductase inhibitor |
| Inclusion Criteria: | Indication associated |
| Strategy ID | Strategy | Synonyms | Related Targets | Related Drugs |
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| Target ID | Target Name | GENE | Action | Class | UniProtKB ID | Entry Name |
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| Diseases ID | DO ID | Disease Name | Definition | Class | |
|---|---|---|---|---|---|
| I01 | 552 | Pneumonia | A lung disease that involves lung parenchyma or alveolar inflammation and abnormal alveolar filling with fluid (consolidation and exudation). It results from a variety of causes including infection with bacteria, viruses, fungi or parasites, and chemical or physical injury to the lungs. It is accompanied by fever, chills, cough, and difficulty in breathing. http://en.wikipedia.org/wiki/Pneumonia | disease of anatomical entity/respiratory system disease/ lower respiratory tract disease/lung disease | Details |