DDInter1008 DDInter1628
Ketoconazole is an imidazole antifungal agent used in the prevention and treatment of a variety of fungal infections.[FDA Label] It functions by preventing the synthesis of ergosterol, the fungal equivalent of cholesterol, thereby increasing membrane fluidity and preventing growth of the fungus.[A181802,T116] Ketoconazole was first approved in an oral formulation for systemic use by the FDA in 1981. At this time it was considered a significant improvement over previous antifungals, [miconazole] and [clotrimazole], due to its broad spectrum and good absorption. However, it was discovered that ketoconazole produces frequent gastrointestinal side effects and dose-related hepatitis.[A188054,A188057] These effects combined with waning efficacy led to its eventual replacement by triazole agents, [fluconazole], [itraconazole], [voriconazole], and [posaconazole]. Ketoconazole and its predecessor [clotrimazole] continue
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.
Ketoconazole {u} (Compound) binds {v} (Gene) CYP3A4
CYP3A4 {u} (Gene) is bound by {v} (Compound) Ruxolitinib
Ketoconazole {u} (Compound) upregulates {v} (Gene) HMGCR
HMGCR {u} (Gene) is upregulated by {v} (Compound) Ruxolitinib
Ketoconazole {u} (Compound) upregulates {v} (Gene) SLC2A6
SLC2A6 {u} (Gene) is downregulated by {v} (Compound) Ruxolitinib
Ketoconazole {u} (Compound) causes {v} (Side Effect) Fatigue
Fatigue {u} (Side Effect) is caused by {v} (Compound) Ruxolitinib
Ketoconazole {u} (Compound) upregulates {v} (Gene) HMGCR
HMGCR {u} (Gene) regulates {v} (Gene) DUSP4
DUSP4 {u} (Gene) is upregulated by {v} (Compound) Ruxolitinib
Ketoconazole {u} (Compound) upregulates {v} (Gene) SLC2A6
SLC2A6 {u} (Gene) is regulated by {v} (Gene) CTCF
CTCF {u} (Gene) is upregulated by {v} (Compound) Ruxolitinib
Ketoconazole {u} (Compound) resembles {v} (Compound) Itraconazole
Itraconazole {u} (Compound) binds {v} (Gene) CYP3A4
CYP3A4 {u} (Gene) is bound by {v} (Compound) Ruxolitinib
Ketoconazole {u} (Compound) upregulates {v} (Gene) SLC2A6
SLC2A6 {u} (Gene) regulates {v} (Gene) PRAF2
PRAF2 {u} (Gene) is downregulated by {v} (Compound) Ruxolitinib
Ketoconazole {u} (Compound) resembles {v} (Compound) Itraconazole
Itraconazole {u} (Compound) causes {v} (Side Effect) Fatigue
Fatigue {u} (Side Effect) is caused by {v} (Compound) Ruxolitinib
Ketoconazole {u} (Compound) upregulates {v} (Gene) SLC2A6
SLC2A6 {u} (Gene) is regulated by {v} (Gene) AMDHD2
AMDHD2 {u} (Gene) is downregulated by {v} (Compound) Ruxolitinib
Ketoconazole (Compound) binds CYP3A4 (Gene) and CYP3A4 (Gene) is bound by Ruxolitinib (Compound)
Ketoconazole (Compound) upregulates HMGCR (Gene) and HMGCR (Gene) is upregulated by Ruxolitinib (Compound)
Ketoconazole (Compound) upregulates SLC2A6 (Gene) and SLC2A6 (Gene) is downregulated by Ruxolitinib (Compound)
Ketoconazole (Compound) causes Fatigue (Side Effect) and Fatigue (Side Effect) is caused by Ruxolitinib (Compound)
Ketoconazole (Compound) upregulates HMGCR (Gene) and HMGCR (Gene) regulates DUSP4 (Gene) and DUSP4 (Gene) is upregulated by Ruxolitinib (Compound)
Ketoconazole (Compound) upregulates SLC2A6 (Gene) and SLC2A6 (Gene) is regulated by CTCF (Gene) and CTCF (Gene) is upregulated by Ruxolitinib (Compound)
Ketoconazole (Compound) resembles Itraconazole (Compound) and Itraconazole (Compound) binds CYP3A4 (Gene) and CYP3A4 (Gene) is bound by Ruxolitinib (Compound)
Ketoconazole (Compound) upregulates SLC2A6 (Gene) and SLC2A6 (Gene) regulates PRAF2 (Gene) and PRAF2 (Gene) is downregulated by Ruxolitinib (Compound)
Ketoconazole (Compound) resembles Itraconazole (Compound) and Itraconazole (Compound) causes Fatigue (Side Effect) and Fatigue (Side Effect) is caused by Ruxolitinib (Compound)
Ketoconazole (Compound) upregulates SLC2A6 (Gene) and SLC2A6 (Gene) is regulated by AMDHD2 (Gene) and AMDHD2 (Gene) is downregulated by Ruxolitinib (Compound)