DDInter1087 DDInter1628
Hutchinson-Gilford progeria syndrome (HGPS) is a rare autosomal dominant disorder estimated to affect approximately one in 20 million individuals resulting in adverse symptoms associated with premature ageing: skeletal dysplasia, joint contractures, atherosclerosis, myocardial fibrosis/dysfunction, scleroderma-like cutaneous effects, lipoatrophy, alopecia, and a severe failure to thrive; HGPS is uniformly fatal.[A224379, A224384, A224389, A224394, A224399] Mechanistically, HGPS is underpinned by a single heterozygous C-to-T mutation at position 1824 of the _LMNA_ gene, which results in the accumulation of an aberrant farnesylated form of lamin A called progerin in the inner nuclear membrane.[A224379, A224394] Lonafarnib is a farnesyl transferase (FTase) inhibitor (FT
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.
Lonafarnib {u} may cause a minor interaction that can limit clinical effects when taken with {v} Sibutramine
Sibutramine {u} (Compound) binds {v} (Gene) CYP3A4
CYP3A4 {u} (Gene) is bound by {v} (Compound) Ruxolitinib
Lonafarnib {u} may cause a moderate interaction that could exacerbate diseases when taken with {v} Loratadine
Loratadine {u} (Compound) binds {v} (Gene) CYP3A4
CYP3A4 {u} (Gene) is bound by {v} (Compound) Ruxolitinib
Lonafarnib {u} may cause a minor interaction that can limit clinical effects when taken with {v} Sibutramine
Sibutramine {u} (Compound) causes {v} (Side Effect) Anaemia
Anaemia {u} (Side Effect) is caused by {v} (Compound) Ruxolitinib
Lonafarnib {u} may cause a moderate interaction that could exacerbate diseases when taken with {v} Nitisinone
Nitisinone {u} (Compound) causes {v} (Side Effect) Haemoglobin
Haemoglobin {u} (Side Effect) is caused by {v} (Compound) Ruxolitinib
Lonafarnib {u} may cause a moderate interaction that could exacerbate diseases when taken with {v} Teniposide
Teniposide {u} (Compound) treats {v} (Disease) hematologic cancer
hematologic cancer {u} (Disease) is treated by {v} (Compound) Ruxolitinib
Lonafarnib {u} may cause a moderate interaction that could exacerbate diseases when taken with {v} Teniposide
Teniposide {u} (Compound) upregulates {v} (Gene) PLK3
PLK3 {u} (Gene) is bound by {v} (Compound) Ruxolitinib
Lonafarnib {u} may cause a moderate interaction that could exacerbate diseases when taken with {v} Teniposide
Teniposide {u} (Compound) downregulates {v} (Gene) PLK4
PLK4 {u} (Gene) is bound by {v} (Compound) Ruxolitinib
Lonafarnib {u} may cause a moderate interaction that could exacerbate diseases when taken with {v} Flunisolide
Flunisolide {u} (Compound) downregulates {v} (Gene) DUSP4
DUSP4 {u} (Gene) is upregulated by {v} (Compound) Ruxolitinib
Lonafarnib {u} may cause a moderate interaction that could exacerbate diseases when taken with {v} Flunisolide
Flunisolide {u} (Compound) upregulates {v} (Gene) NFKBIA
NFKBIA {u} (Gene) is upregulated by {v} (Compound) Ruxolitinib
Lonafarnib {u} may cause a moderate interaction that could exacerbate diseases when taken with {v} Cabazitaxel
Cabazitaxel {u} (Compound) binds {v} (Gene) CYP3A4
CYP3A4 {u} (Gene) is bound by {v} (Compound) Ruxolitinib
Lonafarnib may cause a minor interaction that can limit clinical effects when taken with Sibutramine and Sibutramine (Compound) binds CYP3A4 (Gene) and CYP3A4 (Gene) is bound by Ruxolitinib (Compound)
Lonafarnib may cause a moderate interaction that could exacerbate diseases when taken with Loratadine and Loratadine (Compound) binds CYP3A4 (Gene) and CYP3A4 (Gene) is bound by Ruxolitinib (Compound)
Lonafarnib may cause a minor interaction that can limit clinical effects when taken with Sibutramine and Sibutramine (Compound) causes Anaemia (Side Effect) and Anaemia (Side Effect) is caused by Ruxolitinib (Compound)
Lonafarnib may cause a moderate interaction that could exacerbate diseases when taken with Nitisinone and Nitisinone (Compound) causes Haemoglobin (Side Effect) and Haemoglobin (Side Effect) is caused by Ruxolitinib (Compound)
Lonafarnib may cause a moderate interaction that could exacerbate diseases when taken with Teniposide and Teniposide (Compound) treats hematologic cancer (Disease) and hematologic cancer (Disease) is treated by Ruxolitinib (Compound)
Lonafarnib may cause a moderate interaction that could exacerbate diseases when taken with Teniposide and Teniposide (Compound) upregulates PLK3 (Gene) and PLK3 (Gene) is bound by Ruxolitinib (Compound)
Lonafarnib may cause a moderate interaction that could exacerbate diseases when taken with Teniposide and Teniposide (Compound) downregulates PLK4 (Gene) and PLK4 (Gene) is bound by Ruxolitinib (Compound)
Lonafarnib may cause a moderate interaction that could exacerbate diseases when taken with Flunisolide and Flunisolide (Compound) downregulates DUSP4 (Gene) and DUSP4 (Gene) is upregulated by Ruxolitinib (Compound)
Lonafarnib may cause a moderate interaction that could exacerbate diseases when taken with Flunisolide and Flunisolide (Compound) upregulates NFKBIA (Gene) and NFKBIA (Gene) is upregulated by Ruxolitinib (Compound)
Lonafarnib may cause a moderate interaction that could exacerbate diseases when taken with Cabazitaxel and Cabazitaxel (Compound) binds CYP3A4 (Gene) and CYP3A4 (Gene) is bound by Ruxolitinib (Compound)