Drug intelligence / Profile preview

decitabine + methotrexate + l-asparaginase + dexamethasone + aclacinomycin

Development stage
Unknown
Lead developer
Tongji Hospital, Huazhong University of Science and Technology
Modality
Small Molecules, Recombinant Proteins and Enzymes
Administration
Intravenous
01

Overview

D-MAAL is a combination chemotherapy regimen consisting of the hypomethylating agent decitabine and the MAAL backbone (methotrexate, aclacinomycin, L-asparaginase, and dexamethasone). Developed by researchers at the Department of Hematology, Tongji Hospital of Huazhong University of Science and Technology, this regimen is primarily investigated for the treatment of relapsed or refractory T-cell lymphoblastic lymphoma (T-LBL). The therapeutic rationale involves using decitabine as an epigenetic primer to sensitize malignant T-cells to the cytotoxic effects of the MAAL components. Decitabine acts by inhibiting DNA methyltransferase, leading to DNA hypomethylation and the reactivation of silenced tumor suppressor genes. Methotrexate serves as an antimetabolite by inhibiting dihydrofolate reductase, while aclacinomycin (aclarubicin) acts as a DNA intercalator and topoisomerase II inhibitor. L-asparaginase depletes systemic asparagine, an essential amino acid for leukemic cells, and dexamethasone induces apoptosis through glucocorticoid receptor activation.

Other names
D-MAAL regimenDecitabine-MAAL
02

Targets

26S proteasomeDNMT1 (DNA (cytosine-5)-methyltransferase 1)DNMT3B (DNA (cytosine-5)-methyltransferase 3B)TOP1 (DNA Topoisomerase I)TOP2A (DNA topoisomerase II)DHFR (Dihydrofolate reductase)GR (Glucocorticoid receptor)

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