. 2019 Mar 22;24(6):1140. doi: 10.3390/molecules24061140

Table 1.

DHFR inhibitors that have been approved [36].

Antifolate	Status *	Indication	Toxicity
Methotrexate	Approved by FDA and EMA in 1985	Treatment of lymphoma, acute lymphoblastic leukemia and osteosarcoma	Symptoms of overdose include bone marrow suppression and gastrointestinal side effects
Raltitrexed	Approved by EMA in 1998	Treatment of malignant colorectal cancer, but its utilization in mainly limited to patients who are intolerant to 5-fluorouracil	Gastrointestinal and hematologic side effects
Pemetrexed	Approved by FDA and EMA in 2001	First-line treatment for advanced non-squamous-cell lung cancer and pleural mesothelioma in combination with cisplatin	Neutropenia, leukopenia, anemia, stomatitis and infection
Pralatrexate	Approved by FDA and EMA in 2009	Treatment of relapsed or refractory peripheral T-cell lymphoma (TCL)	Mucositis