DDInter1174 DDInter1628
Methotrexate is a folate derivative that inhibits several enzymes responsible for nucleotide synthesis. This inhibition leads to suppression of inflammation as well as prevention of cell division. Because of these effects, methotrexate is often used to treat inflammation caused by arthritis or to control cell division in neoplastic diseases such as breast cancer and non-Hodgkin's lymphoma.[A180322,L7144,L7147,L7150,L7180] Due to the toxic effects of methotrexate, it is indicated for treatment of some forms of arthritis and severe psoriasis only if first line treatment has failed or patients are intolerant of those treatments. Methotrexate was granted FDA approval on 7 December 1953.
Ruxolitinib, formerly known as INCB018424 or INC424, is an anticancer drug and a Janus kinase (JAK) inhibitor. It is a potent and selective inhibitor of JAK1 and JAK2, which are tyrosine kinases involved in cytokine signalling and hematopoiesis. Myeloproliferative neoplasms, such as myelofibrosis and polycythemia vera, are often characterized by aberrant activation of the JAK-STAT pathway, leading to abnormal blood cell counts and thrombotic complications. By inhibiting JAK1 and JAK2, ruxolitinib works to block the dysregulated cell signalling pathways and prevents abnormal blood cell proliferation. Due to a large number of patients with myeloproliferative neoplasms who have JAK2 mutations, ruxolitinib was the first ATP-competitive inhibitor of JAK1 and JAK2 ever developed. Ruxolitinib was first approved for the treatment of adult patients with myelofibrosis by the FDA in 2011, followed by EMA's approval in 2012. In 2014, it was approved for the treatment of polycythemia vera in adults who have an inadequate response to or are intolerant of [hydroxyurea] and in 2019, ruxolitinib was approved for use in steroid-refractory acute graft-versus-host disease in adults and children. The topical formulation of ruxolitinib is used to treat atopic dermatitis and vitiligo. It is being investigated for other inflammatory skin conditions. Ruxolitinib has been investigated to treat patients with coronavirus disease 2019 (COVID-19) accompanied by severe systemic hyperinflammation. In phase II clinical trials, ruxolitinib improved chest computed tomography and improved recovery in patients with lymphopenia.[A229713, A229718] However, phase III clinical trials later determined that ruxolitinib was inadequate in meeting its primary endpoint of reducing the number of hospitalized COVID-19 patients who experienced severe complications thus the drug was not approved as a treatment for COVID-19.
Methotrexate {u} (Compound) treats {v} (Disease) hematologic cancer
hematologic cancer {u} (Disease) is treated by {v} (Compound) Ruxolitinib
Methotrexate {u} (Compound) downregulates {v} (Gene) PLK1
PLK1 {u} (Gene) is bound by {v} (Compound) Ruxolitinib
Methotrexate {u} (Compound) upregulates {v} (Gene) DUSP4
DUSP4 {u} (Gene) is upregulated by {v} (Compound) Ruxolitinib
Methotrexate {u} (Compound) downregulates {v} (Gene) TCERG1
TCERG1 {u} (Gene) is upregulated by {v} (Compound) Ruxolitinib
Methotrexate {u} (Compound) upregulates {v} (Gene) AMDHD2
AMDHD2 {u} (Gene) is downregulated by {v} (Compound) Ruxolitinib
Methotrexate {u} (Compound) downregulates {v} (Gene) NUP88
NUP88 {u} (Gene) is downregulated by {v} (Compound) Ruxolitinib
Methotrexate {u} (Compound) causes {v} (Side Effect) Anaemia
Anaemia {u} (Side Effect) is caused by {v} (Compound) Ruxolitinib
Methotrexate {u} (Compound) treats {v} (Disease) hematologic cancer
hematologic cancer {u} (Disease) is associated with {v} (Gene) JAK1
JAK1 {u} (Gene) is bound by {v} (Compound) Ruxolitinib
Methotrexate {u} (Compound) downregulates {v} (Gene) PLK1
PLK1 {u} (Gene) is regulated by {v} (Gene) LRRK2
LRRK2 {u} (Gene) is bound by {v} (Compound) Ruxolitinib
Methotrexate {u} (Compound) upregulates {v} (Gene) DUSP4
DUSP4 {u} (Gene) is regulated by {v} (Gene) RET
RET {u} (Gene) is bound by {v} (Compound) Ruxolitinib
Methotrexate (Compound) treats hematologic cancer (Disease) and hematologic cancer (Disease) is treated by Ruxolitinib (Compound)
Methotrexate (Compound) downregulates PLK1 (Gene) and PLK1 (Gene) is bound by Ruxolitinib (Compound)
Methotrexate (Compound) upregulates DUSP4 (Gene) and DUSP4 (Gene) is upregulated by Ruxolitinib (Compound)
Methotrexate (Compound) downregulates TCERG1 (Gene) and TCERG1 (Gene) is upregulated by Ruxolitinib (Compound)
Methotrexate (Compound) upregulates AMDHD2 (Gene) and AMDHD2 (Gene) is downregulated by Ruxolitinib (Compound)
Methotrexate (Compound) downregulates NUP88 (Gene) and NUP88 (Gene) is downregulated by Ruxolitinib (Compound)
Methotrexate (Compound) causes Anaemia (Side Effect) and Anaemia (Side Effect) is caused by Ruxolitinib (Compound)
Methotrexate (Compound) treats hematologic cancer (Disease) and hematologic cancer (Disease) is associated with JAK1 (Gene) and JAK1 (Gene) is bound by Ruxolitinib (Compound)
Methotrexate (Compound) downregulates PLK1 (Gene) and PLK1 (Gene) is regulated by LRRK2 (Gene) and LRRK2 (Gene) is bound by Ruxolitinib (Compound)
Methotrexate (Compound) upregulates DUSP4 (Gene) and DUSP4 (Gene) is regulated by RET (Gene) and RET (Gene) is bound by Ruxolitinib (Compound)