This panel provides drug-protein interaction and their ADRs along with references
| Toxicity |
Interacting Protein |
Mechanism |
Reference |
| Cardiac Malfunctions | Cytochrome c oxidase (P00395) | ddC treatment provoked a surprisingly rapid appearance of cardiac malfunctions characterized by significantly decreased activity of respiratory complexes (NADH: cytochrome c oxidoreductase and cytochrome oxidase) [ ADR Type 2 ] | Molecular mechanism of the short-term cardiotoxicity caused by 2',3'-dideoxycytidine (ddC): modulation of reactive oxygen species levels and ADP-ribosylation reactions
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| Cardiac Malfunctions | NADH-cytochrome c reductase isoform (Q9UHQ9) | ddC treatment provoked a surprisingly rapid appearance of cardiac malfunctions characterized by significantly decreased activity of respiratory complexes (NADH: cytochrome c oxidoreductase and cytochrome oxidase). [ ADR Type 2 ] | Molecular mechanism of the short-term cardiotoxicity caused by 2',3'-dideoxycytidine (ddC): modulation of reactive oxygen species levels and ADP-ribosylation reactions
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| Cardiotoxicity | Desmin (P17661) | An activation of the nuclear poly-(ADP-ribose) polymerase and an increase in the mono-ADP-ribosylation of glucose-regulated protein and desmin were observed in the cardiac tissue from ddC-treated animals@which suggests that the short term cardiotoxicity of ddC is partially based on ROS-mediated signalling. [ ADR Type 2 ] | Molecular mechanism of the short-term cardiotoxicity caused by 2',3'-dideoxycytidine (ddC): modulation of reactive oxygen species levels and ADP-ribosylation reactions
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| Cardiotoxicity | glucose-regulated protein (P11021) | An activation of the nuclear poly-(ADP-ribose) polymerase and an increase in the mono-ADP-ribosylation of glucose-regulated protein and desmin were observed in the cardiac tissue from ddC-treated animals@which suggests that the short term cardiotoxicity of ddC is partially based on ROS-mediated signalling. [ ADR Type 2 ] | Molecular mechanism of the short-term cardiotoxicity caused by 2',3'-dideoxycytidine (ddC): modulation of reactive oxygen species levels and ADP-ribosylation reactions
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| Cardiotoxicity | Heat shock 70 kDa protein (O43301) | A decrease in the quantity of heat shock protein (HSP)70s was also detected,which suggests that the short term cardiotoxicity of ddC is partially based on ROS-mediated signalling. [ ADR Type 2 ] | Molecular mechanism of the short-term cardiotoxicity caused by 2',3'-dideoxycytidine (ddC): modulation of reactive oxygen species levels and ADP-ribosylation reactions
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| Cardiotoxicity | Myoglobin (P02144) | ddC treatment induced a skeletal muscle-specific decrease in the quantity of myoglobin,which suggests that the short term cardiotoxicity of ddC is partially based on ROS-mediated signalling [ ADR Type 5 ] | Molecular mechanism of the short-term cardiotoxicity caused by 2',3'-dideoxycytidine (ddC): modulation of reactive oxygen species levels and ADP-ribosylation reactions
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| Cardiotoxicity | Poly [ADP-ribose] polymerase (P09874) | An activation of the nuclear poly-(ADP-ribose) polymerase and an increase in the mono-ADP-ribosylation of glucose-regulated protein and desmin were observed in the cardiac tissue from ddC-treated animals@which suggests that the short term cardiotoxicity of ddC is partially based on ROS-mediated signalling. [ ADR Type 2 ] | Molecular mechanism of the short-term cardiotoxicity caused by 2',3'-dideoxycytidine (ddC): modulation of reactive oxygen species levels and ADP-ribosylation reactions
|
| Cardiotoxicity | Triosephosphate isomerase (P60174) | ddC treatment induced a skeletal muscle-specific decrease in the quantity of triosephosphate isomerase@which suggests that the short term cardiotoxicity of ddC is partially based on ROS-mediated signalling [ ADR Type 5 ] | Molecular mechanism of the short-term cardiotoxicity caused by 2',3'-dideoxycytidine (ddC): modulation of reactive oxygen species levels and ADP-ribosylation reactions
|
| Cytotoxicity | Cytochrome c oxidase subunit 4 (P13073) | Increase lactate production and decrease activities of COX (complex IV) and SDH (part of complex II)@are the most potent inhibitors of mitochondrial function@thus AZT@ ddI and ddC all exert Cytotoxicity on human muscle cells and induce functional alterations of mitochondria possibly due to mechanisms other than the sole mtDNA depletion [ ADR Type 1 ] | Cellular and mitochondrial toxicity of zidovudine (AZT), didanosine (ddI) and zalcitabine (ddC) on cultured human muscle cells
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| Intestinal Disorder | Oxytocin receptor (P30559) | IFN-alpha induce a 35-50% decrease in OTR mRNA and protein and that this inhibition was time and dose dependent so a temperature-sensitive mutation in an intestinal enzyme deficiency or an intestinal disorder [ ADR Type 1 ] | Interferon-alpha downregulates expression of the oxytocin receptor in cultured human myometrial cells
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| Mtdna Depletion | DNA-directed RNA polymerase mitochondrial (O00411) | Zalcitabine can inhibit mitochondrial (mt)DNA polymerase and cause termination of synthesis of growing mtDNA strands and mtDNA depletion [ ADR Type 1 ] | Cellular and mitochondrial toxicity of zidovudine (AZT), didanosine (ddI) and zalcitabine (ddC) on cultured human muscle cells
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| Tumor Suppression | wild-type p53 (P04637) | Those patients with a mutated p53 did not enter remission of tumor suppression following treatment with ddC and patients disease relapse was associated with the selection of a tumor clone carrying mutated inactive p53. [ ADR Type 2 ] | Persistent inhibition of telomerase reprograms adult T-cell leukemia to p53-dependent senescence
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