Pathways

Metabolites of Darunavir are predicted with biotransformer.

Dasabuvir is a direct-acting antiviral agent used to treat specific hepatitis C virus (HCV) infections in combination with other antiviral agents, Ombitasvir, Paritaprevir, and Ritonavir. Hepatitis C virus lipoviroparticles enter target hepatocytes via receptor-mediated endocytosis. The lipoviroparticles attach to LDL-R and SR-B1, and then the virus binds to CD81 and subsequently claudin-1 and occludin, which mediate the late steps of viral entry. The virus is internalized by clathrin-dependent endocytosis. RNA is released from the mature Hepatitis C virion and translated at the rough endoplasmic reticulum into a single Genome polyprotein. The genome polyprotein is cleaved by host and viral proteases into 10 viral proteins. The nucleocapsid protein core and the two envelope proteins E1 and E2 form the N terminus of the polyprotein and are the structural components of HCV virions. The precursor also gives rise to the viroporin p7 and six non-structural (NS) proteins. Dasabuvir is an inhibitor of the Hepatitis C Virus (HCV) Nonstructural protein 5B, which is an RNA-dependent RNA polymerase. RNA polymerase is required for viral RNA replication and assembly of HCV virions. By binding to nonstructural protein 5B outside of the active site of the enzyme, dasabuvir induces a conformational change. Viral RNA replication complexes localize to lipid raft-containing, detergent-resistant membranes created by the viral protein NS4B. For full viral replication and maturation, nonstructural protein 5B is required so viral RNA replication cannot occur. Envelope glycoproteins are acquired through budding into the endoplasmic reticulum lumen. The immature, non-infective virions are released via the cellular golgi apparatus.

Metabolites of Dasabuvir are predicted with biotransformer.

Dasatinib is a tyrosine kinase inhibitor used to treat chronic myelogenous leukemia (CML), a cancer characterized by increased and unregulated growth of white blood cells in the bone marrow and the accumulation of these cells in the blood and acute lymphoblastic leukemia . The cause of CML pathophysiology is the BCR-ABL fusion protein - the result of a genetic abnormality known as the Philadelphia chromosome in which Abelson Murine Leukemia viral oncogene homolog 1 (ABL1) translocates within the Breakpoint Cluster Region (BCR) gene on chromosome 22. BCR-ABL is a cytoplasm-targeted constitutively active tyrosine kinase that activates several oncogenic pathways which promote increased cell proliferation and survival including the MAPK/ERK Pathway, the JAK-STAT Pathway, and the PI3K/Akt pathway. For greater detail, refer to the pathway titled BCR-ABL Action in CML Pathogenesis. Dasatinib is able to bind ABL with greater affinity than Imatinib (25-55 times more potent). It is therefore administered to patients with Imatinib resistance.

Dasatinib is a tyrosine kinase inhibitor used to treat chronic myelogenous leukemia (CML), a cancer characterized by increased and unregulated growth of white blood cells in the bone marrow and the accumulation of these cells in the blood. The cause of CML pathophysiology is the BCR-ABL fusion protein - the result of a genetic abnormality known as the Philadelphia chromosome in which Abelson Murine Leukemia viral oncogene homolog 1 (ABL1) translocates within the Breakpoint Cluster Region (BCR) gene on chromosome 22. BCR-ABL is a cytoplasm-targeted constitutively active tyrosine kinase that activates several oncogenic pathways which promote increased cell proliferation and survival including the MAPK/ERK Pathway, the JAK-STAT Pathway, and the PI3K/Akt pathway. Dasatinib is considered a second generation BCR-ABL inhibitor (Imatinib being the progenitor) that inhibits BCR-ABL activity by binding a highly conserved ATP binding site to effectively lock the tyrosine kinase in an inactive conformation. As a result, phosphate is unable to be transferred from ATP to activate oncogenic signalling cascades. For greater detail, refer to the pathway titled BCR-ABL Action in CML Pathogenesis. Dasatinib is able to bind ABL with greater affinity than Imatinib, partly owing to its ability to recognize multiple states of the enzyme. It is therefore administered to patients with Imatinib resistance. Notably, Dasatinib is ineffective against the T315I mutation in BCR-ABL, and further research is necessary.

Metabolites of Dasatinib are predicted with biotransformer.

Daunorubicin is an aminoglycoside used to induce remission of nonlymphocytic leukemia and acute lymphocytic leukemia (ALL). This drug is a very toxic anthracycline antineoplastic isolated from Streptomyces peucetius and is administered by injection into a vein. It inhibits cellular reproduction by interfering with DNA replication. Also, it may contribute to the induction of apoptosis by increasing the oxidative stress of the cell through the generation of reactive oxygen species and free radicals. Daunorubicin carries significant toxicities including cytopenias, hepatotoxicity, and extravasation reactions. Like other anthracyclines, daunorubicin exhibits cardiotoxicity that is in proportion to the cumulative dose of the drug. Daunorubicin acts by forming many complexes with DNA, by intercalation between base pairs, and it inhibits topoisomerase II (2-alpha and 2-beta) activity by stabilizing the DNA-topoisomerase II complex, preventing the religation portion of the ligation-religation reaction that topoisomerase II normally catalyzes. By doing this, the cell will not be able to continue its replication and will die through apoptosis.