Ligand id: 4815

Name: methotrexate

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Structure and Physico-chemical Properties

2D Structure
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Calculated Physico-chemical Properties
Hydrogen bond acceptors 13
Hydrogen bond donors 5
Rotatable bonds 10
Topological polar surface area 210.54
Molecular weight 454.17
XLogP -2.67
No. Lipinski's rules broken 1

Molecular properties generated using the CDK

No information available.
Summary of Clinical Use
Anti-tumour agent used in the treatment of acute lymphocytic leukemia (ALL), meningeal leukemia, non-Hogkin's lymphoma, breast, lung and head and neck cancers. Also indicated in the treatment of gestational choriocarcinoma, chorioadenoma destruens and hydatidiform mole, and in the treatment of autoimmune conditions including severe psoriasis and rheumatoid arthritis. The first oral methotraxate solution (Xatmep®) was FDA approved in April 2017 for the treatment of ALL and polyarticular juvenile idiopathic arthritis (pJIA) in pediatric patients. A 2017 a paper reported that a combination of methotrexate with leflunomide relieves the immune defects and ameliorates symptoms of rheumatoid arthritis [7].
Mechanism Of Action and Pharmacodynamic Effects
The mechanism(s) of action of methotrexate are related to its action as an inhibitor of various folate pathway enzymes. Inhibition of DHFR leads to the inhibition of DNA synthesis and cellular replication, and produces an anti-proliferative outcome. Inhibition of ATIC is involved in methotrexate's anti-inflammatory effect.
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