| Drug Name: | Etoposide (33419-42-0) |
|---|---|
| PubChem ID: | 57369479 |
| SMILES: | [2H]C([2H])([2H])OC1=C(C(=CC(=C1)[C@H]2[C@@H]3C(COC3=O)C(C4=CC5=C(C=C24)OCO5)O[C@H]6[C@H]([C@H]([C@H]7C(O6)COC(O7)C)O)O)OC)O |
| InchiKey: | VJJPUSNTGOMMGY-WWPGOOPGSA-N |
| Therapeutic Category: | Antineoplastic Agents, Enzyme Inhibitors, Topoisomerase II Inhibitors, Topoisomerase Inhibitors |
| Molecular Weight (dalton) | : | 591.58 |
| LogP | : | 1.3386 |
| Ring Count | : | 2 |
| Hydrogen Bond Acceptor Count | : | 13 |
| Hydrogen Bond Donor Count | : | 3 |
| Total Polar Surface Area | : | 160.83 |
This panel provides information on interacting drugs and their ADRs along with references
| Interacting drug | Toxicity | Interaction Type | Mechanism | Reference |
|---|---|---|---|---|
| Atovaquone (95233-18-4) | Acute Myeloid Leukaemia | Synergistic | Unclear | The effect of atovaquone on etoposide pharmacokinetics in children with acute lymphoblastic leukemia |
| Cyclosporine (59865-13-3) | Hepatotoxicity | Synergistic | ciclosporin decreases the metabolism of the etoposide by inhibiting its metabolism by cytochrome P450 isoenzymes6 and inhibiting P-glycoprotein mediated efflux from the hepatocyte, | A Study on the Metabolism of Etoposide and Possible Interactions with Antitumor or Supporting Agents by Human Liver Microsomes |
| Cyclosporine (59865-13-3) | Mental Confusion | Synergistic | ciclosporin decreases the metabolism of the etoposide by inhibiting its metabolism by cytochrome P450 isoenzymes6 and inhibiting P-glycoprotein mediated efflux from the hepatocyte, | A Study on the Metabolism of Etoposide and Possible Interactions with Antitumor or Supporting Agents by Human Liver Microsomes |
| Cyclosporine (59865-13-3) | Toxicity Renal | Synergistic | ciclosporin decreases the metabolism of the etoposide by inhibiting its metabolism by cytochrome P450 isoenzymes6 and inhibiting P-glycoprotein mediated efflux from the hepatocyte, | A Study on the Metabolism of Etoposide and Possible Interactions with Antitumor or Supporting Agents by Human Liver Microsomes |
| Ketoconazole (65277-42-1) | Increase The Effects And Toxicity Of Etoposide | Synergistic | inhibit the metabolism (3?-demethylation) of etoposide by the cytochrome P450 isoenzyme CYP3A4 | A Study on the Metabolism of Etoposide and Possible Interactions with Antitumor or Supporting Agents by Human Liver Microsomes |
| Phenobarbital (50-06-6) | Reduced Efficacy | Antagonistic | Unknown | Altered etoposide pharmacokinetics and time to engraftment in pediatric patients undergoingautologous bone marrow transplantation |
| Ritonavir (155213-67-5) | Neutropenia | Synergistic | Protease inhibitors reducing the metabolism of CDE via inhibition of cytochrome P450 enzymes, or inhibition of P-glycoprotein. Inhibitors of CYP3A4 may increase toxicity with etoposide, | Protease inhibitors potentiate chemotherapy-induced neutropenia |
| St JohnÆs wort (84082-80-4) | Depression | Antagonistic | stimulate the hepatic metabolism of etoposide by the cytochrome P450 isoenzyme CYP3A4. | Catalytic inhibition of human DNA topoisomerase II? by hypericin, a naphthodianthrone from St John’s wort (Hypericum perforatum) |
This panel provides drug-protein interaction and their ADRs along with references
| Toxicity | Interacting Protein | Mechanism | Reference |
|---|---|---|---|
| Apoptosis | Abscisic acid-inducible protein kinase (Q02066) | Induction of apoptotic cell death and DNA damage by treatment of U937 cells with etoposide (100 microM) was associated with a modest@ but sustained@ recruitment of the mitogen-activated protein kinases p42-extracellular signal receptor-activated kinase (ERK)1 and p44-extracellular signal receptor-activated kinase 2. [ ADR Type 2 ] | Evidence that the apoptotic actions of etoposide are independent of c-Jun/activating protein-1-mediated transregulation |
| Apoptosis | B-cell receptor-associated protein 31(BAP31) (P51572) | Association of active caspase 8 with the mitochondrial membrane during apoptosis: potential roles in cleaving BAP31 and caspase 3 and mediating mitochondrion-endoplasmic reticulum cross talk in etoposide-induced cell death [ ADR Type 2 ] | Association of active caspase 8 with the mitochondrial membrane during apoptosis: potential roles in cleaving BAP31 and caspase 3 and mediating mitochondrion-endoplasmic reticulum cross talk |
| Apoptosis | Caspase-3 (P42574) | Association of active caspase 8 with the mitochondrial membrane during apoptosis: potential roles in cleaving BAP31 and caspase 3 and mediating mitochondrion-endoplasmic reticulum cross talk in etoposide-induced cell death. [ ADR Type 2 ] | Association of active caspase 8 with the mitochondrial membrane during apoptosis: potential roles in cleaving BAP31 and caspase 3 and mediating mitochondrion-endoplasmic reticulum cross talk |
| Apoptosis | Caspase-8 (Q14790) | Association of active caspase 8 with the mitochondrial membrane during apoptosis: potential roles in cleaving BAP31 and caspase 3 and mediating mitochondrion-endoplasmic reticulum cross talk in etoposide-induced cell death [ ADR Type 2 ] | Association of active caspase 8 with the mitochondrial membrane during apoptosis: potential roles in cleaving BAP31 and caspase 3 and mediating mitochondrion-endoplasmic reticulum cross talk |
| Apoptosis | DNA topoisomerase 2-alpha (P11388) | Induction of apoptosis by etoposide and related inhibitors of topoisomerase II is mediated through a cell death pathway that does not require SAPK-dependent recruitment of AP1 [ ADR Type 2 ] | Evidence that the apoptotic actions of etoposide are independent of c-Jun/activating protein-1-mediated transregulation |
| Apoptosis | enzyme p46 (P00013) | Induction of apoptotic cell death and DNA damage by treatment of U937 cells with etoposide (100 microM) was associated with phosphorylation and activation of the c-Jun NH(2)-terminal kinase (JNK1) SAPK enzymes p46 and p54-JNK2 and transient increases in expression of the transcription factor c-Jun, a primary JNK substrate [ ADR Type 2 ] | Evidence that the apoptotic actions of etoposide are independent of c-Jun/activating protein-1-mediated transregulation |
| Apoptosis | Mitogen-activated protein kinase (P45983) | Induction of apoptotic cell death and DNA damage by treatment of U937 cells with etoposide (100 microM) was associated with a modest@ but sustained@ recruitment of the mitogen-activated protein kinases p42-extracellular signal receptor-activated kinase (ERK)1 and p44-extracellular signal receptor-activated kinase 2. [ ADR Type 2 ] | Evidence that the apoptotic actions of etoposide are independent of c-Jun/activating protein-1-mediated transregulation |
| Apoptosis | Mitogen-activated protein kinase(ERK) (P28482) | Induction of apoptotic cell death and DNA damage by treatment of U937 cells with etoposide (100 microM) was associated with a modest@ but sustained@ recruitment of the mitogen-activated protein kinases p42-extracellular signal receptor-activated kinase (ERK)1 and p44-extracellular signal receptor-activated kinase 2 [ ADR Type 2 ] | Evidence that the apoptotic actions of etoposide are independent of c-Jun/activating protein-1-mediated transregulation |
| Cell Cycle Arrest | Retinoblastoma tumor suppressor (Q5J3Q9) | pRb-mediated cell cycle arrest. [ ADR Type 2 ] | Inhibition of topoisomerase IIalpha expression by transforming growth factor-beta1 is abrogated by the papillomavirus E7 protein |
| Cell Death | Caspase-8 (Q14790) | Caspase 8 activation plays a causal role in VP16-induced caspase 3 activation and cell death. [ ADR Type 2 ] | Association of active caspase 8 with the mitochondrial membrane during apoptosis: potential roles in cleaving BAP31 and caspase 3 and mediating mitochondrion-endoplasmic reticulum cross talk |
| Cell Death | Mitogen-activated protein kinase p54-JNK2 (P49186) | Induction of apoptotic cell death and DNA damage by treatment of U937 cells with etoposide (100 microM) was associated with phosphorylation and activation of the c-Jun NH(2)-terminal kinase (JNK1) SAPK enzymes p46 and p54-JNK2 and transient increases in expression of the transcription factor c-Jun@ a primary JNK substrate [ ADR Type 2 ] | Evidence that the apoptotic actions of etoposide are independent of c-Jun/activating protein-1-mediated transregulation |
| Cytotoxicity | Apoptosis regulator Bcl-2 (P10415) | Bcl-2 modulates cytotoxicity of VP-16 between cleavable complex formation and subsequent induction of DNA recombination events [ ADR Type 3 ] | Inhibition of etoposide (VP-16)-induced DNA recombination and mutant frequency by Bcl-2 protein overexpression |
| Dna Damage | Mitogen-activated protein kinase p54-JNK2 (P49186) | Induction of apoptotic cell death and DNA damage by treatment of U937 cells with etoposide (100 microM) was associated with phosphorylation and activation of the c-Jun NH(2)-terminal kinase (JNK1) SAPK enzymes p46 and p54-JNK2 and transient increases in expression of the transcription factor c-Jun@ a primary JNK substrate [ ADR Type 2 ] | Evidence that the apoptotic actions of etoposide are independent of c-Jun/activating protein-1-mediated transregulation |
| Dna Damage | Mitogen-activated protein kinase(ERK) (P28482) | Induction of apoptotic cell death and DNA damage by treatment of U937 cells with etoposide (100 microM) was associated with a modest@ but sustained@ recruitment of the mitogen-activated protein kinases p42-extracellular signal receptor-activated kinase (ERK)1 and p44-extracellular signal receptor-activated kinase 2 [ ADR Type 2 ] | Evidence that the apoptotic actions of etoposide are independent of c-Jun/activating protein-1-mediated transregulation |
| Gi Arrest | Protein E7 (P03129) | Topo IIalpha expression is not affected by TGF-beta1 in cells that fail to underGO G1 arrest because of inactivation of the retinoblastoma tumor suppressor protein (pRb) by the papillomavirus type 16 E7 protein [ ADR Type 2 ] | Inhibition of topoisomerase IIalpha expression by transforming growth factor-beta1 is abrogated by the papillomavirus E7 protein |
| Induced Dna Recombination | Hypoxanthine-guanine phosphoribosyltransferase (P00492) | Hypoxanthine phosphoribosyl transferase (hprt) gene mutations and VP-16-induced mutant frequencies at the hprt locus were 5-10 times less in BCL-2/2 and BCL-2/4 cells than those observed in the V79 or NeoR control cells,which may lead to etoposide (VP-16)-induced DNA recombination [ ADR Type 3 ] | Inhibition of etoposide (VP-16)-induced DNA recombination and mutant frequency by Bcl-2 protein overexpression |
| Leukemia | Myeloid/lymphoid or mixed-lineage leukemia protein (Q9UMN6) | Secondary leukemia after etoposide treatment involved MLL gene rearrangement. [ ADR Type 5 ] | Secondary leukemia after etoposide treatment involved MLL gene rearrangement |
This panel provides drug-food interactions and their ADRs along with references
| Food | Toxicity | Reference |
|---|
This panel provides information on metabolites and their ADRs along with references
| Metabolite | Toxicity | Place of Metabolism | Mechanism | Reference |
|---|---|---|---|---|
| etoposide phenoxyl radicals | Myeloid Leukaemia | Deleterious effects of reactive metabolites |
This panel provides information on drug category