DDInter1840 DDInter287
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.
Capmatinib is a small molecule kinase inhibitor targeted against c-Met (a.k.a. hepatocyte growth factor receptor [HGFR]), a receptor tyrosine kinase that, in healthy humans, activates signaling cascades involved in organ regeneration and tissue repair. Aberrant c-Met activation - via mutations, amplification, and/or overexpression - is known to occur in many types of cancer, and leads to overactivation of multiple downstream signaling pathways such as STAT3, PI3K/ATK, and RAS/MAPK. Mutations in _MET_ have been detected in non-small cell lung cancer (NSCLC), and the prevalence of _MET_ amplification in epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI)-naive patients with NSCLC has been reported to be 1.4% - 21%. This co-occurrence has made c-Met a desirable target in the treatment of NSCLC. Manufactured by Novartis and marketed under the brand name Tabrecta, capmatinib was granted accelerated approval by the FDA on May 6, 2020, for the treatment of NSCLC in patients whose tumors have a mutation that leads to mesenchymal-epithelial transition (MET) exon 14 skipping. The presence of the mutation must be confirmed by an FDA-approved test, such as the FoundationOne CDx assay (manufactured by Foundation Medicine, Inc.), which was approved by the FDA on the same day. As this indication was granted under an accelerated approval, its continued approval is contingent upon verification of capmatinib's benefit in confirmatory trials. Capmatinib was approved by Health Canada on June 8, 2022.
Trabectedin {u} (Compound) binds {v} (Gene) CYP2C9
CYP2C9 {u} (Gene) is bound by {v} (Compound) Pantoprazole
Pantoprazole {u} may cause a minor interaction that can limit clinical effects when taken with {v} Capmatinib
Trabectedin {u} (Compound) causes {v} (Side Effect) Agranulocytosis
Agranulocytosis {u} (Side Effect) is caused by {v} (Compound) Pantoprazole
Pantoprazole {u} may cause a minor interaction that can limit clinical effects when taken with {v} Capmatinib
Trabectedin {u} (Compound) binds {v} (Gene) CYP2C9
CYP2C9 {u} (Gene) is bound by {v} (Compound) Fluconazole
Fluconazole {u} may cause a moderate interaction that could exacerbate diseases when taken with {v} Capmatinib
Trabectedin {u} (Compound) binds {v} (Gene) SRC
SRC {u} (Gene) is upregulated by {v} (Compound) Metformin
Metformin {u} may cause a moderate interaction that could exacerbate diseases when taken with {v} Capmatinib
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 cause a moderate interaction that could exacerbate diseases when taken with {v} Capmatinib
Trabectedin {u} (Compound) causes {v} (Side Effect) Agranulocytosis
Agranulocytosis {u} (Side Effect) is caused by {v} (Compound) Epirubicin
Epirubicin {u} may cause a moderate interaction that could exacerbate diseases when taken with {v} Capmatinib
Trabectedin {u} (Compound) binds {v} (Gene) CYP2E1
CYP2E1 {u} (Gene) is bound by {v} (Compound) Dexamethasone
Dexamethasone {u} may lead to a major life threatening interaction when taken with {v} Capmatinib
Trabectedin {u} (Compound) causes {v} (Side Effect) Agranulocytosis
Agranulocytosis {u} (Side Effect) is caused by {v} (Compound) Clarithromycin
Clarithromycin {u} may lead to a major life threatening interaction when taken with {v} Capmatinib
Trabectedin (Compound) binds CYP2C9 (Gene) and CYP2C9 (Gene) is bound by Pantoprazole (Compound) and Pantoprazole may cause a minor interaction that can limit clinical effects when taken with Capmatinib
Trabectedin (Compound) causes Agranulocytosis (Side Effect) and Agranulocytosis (Side Effect) is caused by Pantoprazole (Compound) and Pantoprazole may cause a minor interaction that can limit clinical effects when taken with Capmatinib
Trabectedin (Compound) binds CYP2C9 (Gene) and CYP2C9 (Gene) is bound by Fluconazole (Compound) and Fluconazole may cause a moderate interaction that could exacerbate diseases when taken with Capmatinib
Trabectedin (Compound) binds SRC (Gene) and SRC (Gene) is upregulated by Metformin (Compound) and Metformin may cause a moderate interaction that could exacerbate diseases when taken with Capmatinib
Trabectedin (Compound) binds SRC (Gene) and SRC (Gene) is bound by Crizotinib (Compound) and SRC (Gene) is upregulated by Crizotinib (Compound) and Crizotinib may cause a moderate interaction that could exacerbate diseases when taken with Capmatinib
Trabectedin (Compound) causes Agranulocytosis (Side Effect) and Agranulocytosis (Side Effect) is caused by Epirubicin (Compound) and Epirubicin may cause a moderate interaction that could exacerbate diseases when taken with Capmatinib
Trabectedin (Compound) binds CYP2E1 (Gene) and CYP2E1 (Gene) is bound by Dexamethasone (Compound) and Dexamethasone may lead to a major life threatening interaction when taken with Capmatinib
Trabectedin (Compound) causes Agranulocytosis (Side Effect) and Agranulocytosis (Side Effect) is caused by Clarithromycin (Compound) and Clarithromycin may lead to a major life threatening interaction when taken with Capmatinib