DDInter1840 DDInter1087
Trabectedin, also referred as ET-743 during its development, is a marine-derived antitumor agent discovered in the Carribean tunicate _Ecteinascidia turbinata_ and now produced synthetically. Trabectedin has a unique mechanism of action. It binds to the minor groove of DNA interfering with cell division and genetic transcription processes and DNA repair machinery. It is approved for use in Europe, Russia and South Korea for the treatment of advanced soft tissue sarcoma. It is currently under evaluation for the treatment of breast cancer, prostate cancer, in addition to pediatric sarcomas. Both the European Commission and the U.S. Food and Drug Administration (FDA) have approved trabectedin as an orphan drug in soft tissue sarcomas and ovarian cancer. On October 23, 2015, the FDA approved trabectedin, (as Yondelis), for the treatment of specific soft tissue sarcomas.
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 (FTI), which reduces the farnesylation of numerous cellular proteins, including progerin; as progerin farnesylation is important for localization to the nuclear membrane, lonafarnib inhibits progerin accumulation and improves symptoms in HGPS patients.[A224379, A224414, A224419, L23414] Merck originally developed Lonafarnib and subsequently licensed it to Eiger Biopharmaceuticals Inc., which currently markets it under the trademark ZOKINVY™.[L23414, L23544] Lonafarnib was granted FDA approval on November 20, 2020, and is the first FDA-approved treatment for HGPS and other related progeroid laminopathies.[L23414, L23549]
Trabectedin {u} (Compound) binds {v} (Gene) SRC
SRC {u} (Gene) is bound by {v} (Compound) Dasatinib
Dasatinib {u} may lead to a major life threatening interaction when taken with {v} Lonafarnib
Trabectedin {u} (Compound) binds {v} (Gene) SRC
SRC {u} (Gene) is upregulated by {v} (Compound) Tamoxifen
Tamoxifen {u} may cause a moderate interaction that could exacerbate diseases when taken with {v} Lonafarnib
Trabectedin {u} (Compound) binds {v} (Gene) CYP2C19
CYP2C19 {u} (Gene) is bound by {v} (Compound) Tolbutamide
Tolbutamide {u} may cause a moderate interaction that could exacerbate diseases when taken with {v} Lonafarnib
Trabectedin {u} (Compound) binds {v} (Gene) SRC
SRC {u} (Gene) is bound by {v} (Compound) Ponatinib
Ponatinib {u} may lead to a major life threatening interaction when taken with {v} Lonafarnib
Trabectedin {u} (Compound) binds {v} (Gene) SRC
SRC {u} (Gene) is upregulated by {v} (Compound) Pazopanib
Pazopanib {u} may lead to a major life threatening interaction when taken with {v} Lonafarnib
Trabectedin {u} (Compound) binds {v} (Gene) SRC
SRC {u} (Gene) is bound by {v} (Compound) and {u} (Gene) is upregulated by {v} (Compound) Crizotinib
Crizotinib {u} may lead to a major life threatening interaction when taken with {v} Lonafarnib
Trabectedin {u} (Compound) binds {v} (Gene) CYP3A4
CYP3A4 {u} (Gene) is bound by {v} (Compound) Sibutramine
Sibutramine {u} may cause a minor interaction that can limit clinical effects when taken with {v} Lonafarnib
Trabectedin {u} (Compound) binds {v} (Gene) SRC
SRC {u} (Gene) is upregulated by {v} (Compound) Toremifene
Toremifene {u} may lead to a major life threatening interaction when taken with {v} Lonafarnib
Trabectedin {u} (Compound) causes {v} (Side Effect) Alanine aminotransferase increased
Alanine aminotransferase increased {u} (Side Effect) is caused by {v} (Compound) Paclitaxel
Paclitaxel {u} may cause a moderate interaction that could exacerbate diseases when taken with {v} Lonafarnib
Trabectedin {u} (Compound) causes {v} (Side Effect) Alanine aminotransferase increased
Alanine aminotransferase increased {u} (Side Effect) is caused by {v} (Compound) Sibutramine
Sibutramine {u} may cause a minor interaction that can limit clinical effects when taken with {v} Lonafarnib
Trabectedin (Compound) binds SRC (Gene) and SRC (Gene) is bound by Dasatinib (Compound) and Dasatinib may lead to a major life threatening interaction when taken with Lonafarnib
Trabectedin (Compound) binds SRC (Gene) and SRC (Gene) is upregulated by Tamoxifen (Compound) and Tamoxifen may cause a moderate interaction that could exacerbate diseases when taken with Lonafarnib
Trabectedin (Compound) binds CYP2C19 (Gene) and CYP2C19 (Gene) is bound by Tolbutamide (Compound) and Tolbutamide may cause a moderate interaction that could exacerbate diseases when taken with Lonafarnib
Trabectedin (Compound) binds SRC (Gene) and SRC (Gene) is bound by Ponatinib (Compound) and Ponatinib may lead to a major life threatening interaction when taken with Lonafarnib
Trabectedin (Compound) binds SRC (Gene) and SRC (Gene) is upregulated by Pazopanib (Compound) and Pazopanib may lead to a major life threatening interaction when taken with Lonafarnib
Trabectedin (Compound) binds SRC (Gene) and SRC (Gene) is bound by Crizotinib (Compound) and SRC (Gene) is upregulated by Crizotinib (Compound) and Crizotinib may lead to a major life threatening interaction when taken with Lonafarnib
Trabectedin (Compound) binds CYP3A4 (Gene) and CYP3A4 (Gene) is bound by Sibutramine (Compound) and Sibutramine may cause a minor interaction that can limit clinical effects when taken with Lonafarnib
Trabectedin (Compound) binds SRC (Gene) and SRC (Gene) is upregulated by Toremifene (Compound) and Toremifene may lead to a major life threatening interaction when taken with Lonafarnib
Trabectedin (Compound) causes Alanine aminotransferase increased (Side Effect) and Alanine aminotransferase increased (Side Effect) is caused by Paclitaxel (Compound) and Paclitaxel may cause a moderate interaction that could exacerbate diseases when taken with Lonafarnib
Trabectedin (Compound) causes Alanine aminotransferase increased (Side Effect) and Alanine aminotransferase increased (Side Effect) is caused by Sibutramine (Compound) and Sibutramine may cause a minor interaction that can limit clinical effects when taken with Lonafarnib