DDInter1840 DDInter905
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.
Idelalisib is a phosphoinositide 3-kinase inhibitor indicated in the treatment of chronic lymphocytic leukemia (CLL), relapsed follicular B-cell non-Hodgkin lymphoma (FL), and relapsed small lymphocytic lymphoma (SLL). For the treatment of relapsed CLL, it is currently indicated as a second-line agent in combination with rituximab in patients for whom rituximab alone would be considered appropriate therapy due to other co-morbidities, while in the treatment of FL and SLL it is intended to be used in patients who have received at least two prior systemic therapies. More specifically, idelalisib targets P110δ, the delta isoform of the enzyme phosphatidylinositol-4,5-bisphosphate 3-kinase, also known as PI-3K. The PI-3Ks are a family of enzymes involved in cellular functions such as cell growth, proliferation, differentiation, motility, survival and intracellular trafficking, which in turn are involved in cancer. In contrast to the other class IA PI3Ks p110α and p110β, p110δ is principally expressed in leukocytes (white blood cells) and is important for the function of T cells, B cell, mast cells and neutrophils. By inhibiting this enzyme, idelalisib induces apoptosis of malignant cells and inhibits several cell signaling pathways, including B-cell receptor (BCR) signaling and C-X-C chemokine receptors type 5 and type 4 signalling, which are involved in trafficking and homing of B-cells to the lymph nodes and bone marrow. Treatment of lymphoma cells with idelalisib has been shown to result in inhibition of chemotaxis and adhesion, and reduced cell viability.
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} Idelalisib
Trabectedin {u} (Compound) binds {v} (Gene) PTGS1
PTGS1 {u} (Gene) is bound by {v} (Compound) Flurbiprofen
Flurbiprofen {u} may cause a moderate interaction that could exacerbate diseases when taken with {v} Idelalisib
Trabectedin {u} (Compound) binds {v} (Gene) SRC
SRC {u} (Gene) is upregulated by {v} (Compound) Trametinib
Trametinib {u} may cause a moderate interaction that could exacerbate diseases when taken with {v} Idelalisib
Trabectedin {u} (Compound) binds {v} (Gene) CYP2C19
CYP2C19 {u} (Gene) is bound by {v} (Compound) Escitalopram
Escitalopram {u} may cause a minor interaction that can limit clinical effects when taken with {v} Idelalisib
Trabectedin {u} (Compound) is included by {v} (Pharmacologic Class) Alkylating Activity
Alkylating Activity {u} (Pharmacologic Class) includes {v} (Compound) Lomustine
Lomustine {u} may cause a moderate interaction that could exacerbate diseases when taken with {v} Idelalisib
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} Idelalisib
Trabectedin {u} (Compound) causes {v} (Side Effect) Alanine aminotransferase increased
Alanine aminotransferase increased {u} (Side Effect) is caused by {v} (Compound) Trametinib
Trametinib {u} may cause a moderate interaction that could exacerbate diseases when taken with {v} Idelalisib
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} Idelalisib
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} Idelalisib
Trabectedin {u} (Compound) causes {v} (Side Effect) Left ventricular dysfunction
Left ventricular dysfunction {u} (Side Effect) is caused by {v} (Compound) Dasatinib
Dasatinib {u} may lead to a major life threatening interaction when taken with {v} Idelalisib
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 Idelalisib
Trabectedin (Compound) binds PTGS1 (Gene) and PTGS1 (Gene) is bound by Flurbiprofen (Compound) and Flurbiprofen may cause a moderate interaction that could exacerbate diseases when taken with Idelalisib
Trabectedin (Compound) binds SRC (Gene) and SRC (Gene) is upregulated by Trametinib (Compound) and Trametinib may cause a moderate interaction that could exacerbate diseases when taken with Idelalisib
Trabectedin (Compound) binds CYP2C19 (Gene) and CYP2C19 (Gene) is bound by Escitalopram (Compound) and Escitalopram may cause a minor interaction that can limit clinical effects when taken with Idelalisib
Trabectedin (Compound) is included by Alkylating Activity (Pharmacologic Class) and Alkylating Activity (Pharmacologic Class) includes Lomustine (Compound) and Lomustine may cause a moderate interaction that could exacerbate diseases when taken with Idelalisib
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 Idelalisib
Trabectedin (Compound) causes Alanine aminotransferase increased (Side Effect) and Alanine aminotransferase increased (Side Effect) is caused by Trametinib (Compound) and Trametinib may cause a moderate interaction that could exacerbate diseases when taken with Idelalisib
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 Idelalisib
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 Idelalisib
Trabectedin (Compound) causes Left ventricular dysfunction (Side Effect) and Left ventricular dysfunction (Side Effect) is caused by Dasatinib (Compound) and Dasatinib may lead to a major life threatening interaction when taken with Idelalisib