| Drug Name: | Cisplatin (15663-27-1) |
|---|---|
| PubChem ID: | |
| SMILES: | CC1=CN(C(=O)NC1=O)C2CC(C(O2)COP(=O)(O)OC3CC(OC3CO)N4C=NC5=C4N=CN=C5N)OP(=O)(O)OCC6C(CC(O6)N7C=NC8=C7N=CN=C8N)OP(=O)(O)OC9C(CC(O9)N1C=NC2=C1NC(=NC2=O)N)O.N.[NH2-].[NH2-].[Pt+2] |
| InchiKey: | UZXRICATRQGMQT-UHFFFAOYSA-N |
| Therapeutic Category: | Antineoplastic Agents, Cross-Linking Reagents, Indicators and Reagents, Radiation-Sensitizing Agents |
| Molecular Weight (dalton) | : | 1427.98 |
| LogP | : | -0.03438 |
| Ring Count | : | 7 |
| Hydrogen Bond Acceptor Count | : | 34 |
| Hydrogen Bond Donor Count | : | 11 |
| Total Polar Surface Area | : | 630.35 |
This panel provides information on interacting drugs and their ADRs along with references
This panel provides drug-protein interaction and their ADRs along with references
| Toxicity | Interacting Protein | Mechanism | Reference |
|---|---|---|---|
| Apoptosis | Caspase-6 (P55212) | Cisplatin (CDDP) specifically induces apoptosis via sequential activation of caspase-8@ -3 and -6 in osteosarcoma. [ ADR Type 2 ] | Cisplatin (CDDP) specifically induces apoptosis via sequential activation of caspase-8, -3 and -6 in osteosarcoma |
| Apoptosis | Caspase-8 (Q14790) | Cisplatin (CDDP) specifically induces apoptosis via sequential activation of caspase-8@ -3 and -6 in osteosarcoma. [ ADR Type 2 ] | Cisplatin (CDDP) specifically induces apoptosis via sequential activation of caspase-8, -3 and -6 in osteosarcoma |
| Apoptosis | Epidermal growth factor receptor precursor (P00533) | Abrogation of cisplatin-induced programmed cell death in human breast cancer cells by epidermal growth factor antisense RNA [ ADR Type 2 ] | Epidermal growth factor receptor family and chemosensitization |
| Apoptosis | MDM2 (murine double minute 2) proteins (P00031) | Wild-type p53 and MDM2 (murine double minute 2) proteins was induced when cis-diamminedichloroplatinum (cisplatin) caused apoptosis in human glioblastoma U87-MG cells [ ADR Type 3 ] | MDM2 protein confers the resistance of a human glioblastoma cell line to cisplatin-induced apoptosis |
| Apoptosis | Mitogen-activated protein kinase (P45983) | Activation of JNK and cell death by cisplatin is mediated by the MEKK1/SEK1 cascade@ since expression of dominant negative expression vectors of these kinases blocked both processes;The increase in JNK activity was necessary for cisplatin-mediated apoptosis but it was dispensable for adriamycin-induced cell death. [ ADR Type 2 ] | Lack of c-Jun activity increases survival to cisplatin |
| Apoptosis | Mitogen-activated protein kinase 14 (Q16539) | p38 was also activated by cisplatin with similar kinetics as JNK [ ADR Type 2 ] | Lack of c-Jun activity increases survival to cisplatin |
| Apoptosis | Mitogen-activated protein kinase(ERK) (P28482) | AP-1 complexes were activated by cisplatin including mainly c-jun/ATF-2 heterodimers suggesting that AP-1-dependent transcription partially mediated cisplatin-induced apoptosis [ ADR Type 2 ] | Lack of c-Jun activity increases survival to cisplatin |
| Apoptosis | wild-type p53 (P04637) | Wild-type p53 and MDM2 (murine double minute 2) proteins was induced when cis-diamminedichloroplatinum (cisplatin) caused apoptosis in human glioblastoma U87-MG cells [ ADR Type 3 ] | MDM2 protein confers the resistance of a human glioblastoma cell line to cisplatin-induced apoptosis |
| Cell Death | Peroxiredoxin-2 (P32119) | Prx II antisense enhanced cisplatin-induced cell death. [ ADR Type 2 ] | Synergistic effect of peroxiredoxin II antisense on cisplatin-induced cell death |
| Cell Death | protein kinases ERK (P00048) | Activation of the mitogen-activated protein kinases ERK1/2 by the chemotherapeutic agent cisplatin has been shown to result in either survival or cell death [ ADR Type 2 ] | Ras-mediated activation of ERK by cisplatin induces cell death independently of p53 in osteosarcoma and neuroblastoma cell lines Cancer |
| Cytotoxicity | protein kinase-C (P00047) | Protein kinase C (PKC)-related signal transduction pathways may modulate cisplatin-induced cytotoxicity. [ ADR Type 2 ] | Role of protein kinase C in cisplatin nephrotoxicity |
| Cytotoxicity | Tumor protein p73 (O15350) | c-Abl and p73 are components of a mismatch-repair-dependent apoptosis pathway which contributes to cisplatin-induced cytotoxicity [ ADR Type 2 ] | The tyrosine kinase c-Abl regulates p73 in apoptotic response to cisplatin-induced DNA damage |
| Cytotoxicity | Tyrosine-protein kinase (Q13882) | c-Abl and p73 are components of a mismatch-repair-dependent apoptosis pathway which contributes to cisplatin-induced cytotoxicity [ ADR Type 2 ] | The tyrosine kinase c-Abl regulates p73 in apoptotic response to cisplatin-induced DNA damage |
| Emesis | Catalase (P04040) | Catalase change significantly in cisplatin-induced emesis in Suncus murinus [ ADR Type 2 ] | Involvement of free radicals in cisplatin-induced emesis in Suncus murinus |
| Emesis | Superoxide dismutase (P00441) | Superoxide dismutase change significantly in cisplatin-induced emesis in Suncus murinus. [ ADR Type 2 ] | Involvement of free radicals in cisplatin-induced emesis in Suncus murinus |
| Hypersensitivity | ATP-binding cassette-type transporter (S9RI25) | Mild hypersensitivity [ ADR Type 5 ] | Role of determinants of cadmium sensitivity in the tolerance of Schizosaccharomyces pombe to cisplatin |
| Hypertrophy In Astrocytic Glioma Cells | Gamma-glutamyltranspeptidase (P19440) | Cisplatin induced gamma-glutamyltransferase up-regulation@ hypertrophy and differentiation in astrocytic glioma cells in culture. [ ADR Type 2 ] | A Cisplatin induced gamma-glutamyltransferase up-regulation, hypertrophy and differentiation in astrocytic glioma cells in culture |
| Hypocalcemia | Osteocalcin (P02818) | High normal intact parathyroid hormone (PTH), elevated mid-region PTH and undetectable osteocalcin levels had already been found before the appearance of obvious symptoms concomitantly associated with moderate hypomagnesemia and hypocalcemia. [ ADR Type 1 ] | Tetany due to hypomagnesemia induced by cisplatin and doxorubicin treatment for synovial sarcoma Intern |
| Hypocalcemia | Parathyroid hormone (P01270) | High normal intact parathyroid hormone (PTH), elevated mid-region PTH and undetectable osteocalcin levels had already been found before the appearance of obvious symptoms concomitantly associated with moderate hypomagnesemia and hypocalcemia [ ADR Type 1 ] | Tetany due to hypomagnesemia induced by cisplatin and doxorubicin treatment for synovial sarcoma Intern |
| Hypomagnesemia | Osteocalcin (P02818) | High normal intact parathyroid hormone (PTH), elevated mid-region PTH and undetectable osteocalcin levels had already been found before the appearance of obvious symptoms concomitantly associated with moderate hypomagnesemia and hypocalcemia. [ ADR Type 1 ] | Tetany due to hypomagnesemia induced by cisplatin and doxorubicin treatment for synovial sarcoma Intern |
| Hypomagnesemia | Parathyroid hormone (P01270) | High normal intact parathyroid hormone (PTH), elevated mid-region PTH and undetectable osteocalcin levels had already been found before the appearance of obvious symptoms concomitantly associated with moderate hypomagnesemia and hypocalcemia [ ADR Type 1 ] | Tetany due to hypomagnesemia induced by cisplatin and doxorubicin treatment for synovial sarcoma Intern |
| Impairment Of Glucose Transporter | Na(+)-pump (P00035) | Glucosuria induced by cisplatin was not due to a direct impairment of Glucose transporter in brush-border membranes but due to an inhibition of Na(+)-pump activity and a decrease in area for active glucose reabsorption in the proximal tubule. [ ADR Type 1 ] | Effect of cisplatin on renal function in rabbits: mechanism of reduced glucose reabsorption |
| Nausea | 5-hydroxytryptamine 3 receptor (P46098) | Nausea and vomiting associated with the use of 5 HT uptake inhibitors are due to stimulation of 5HT3 receptors. [ ADR Type 1 ] | Litoxetine: a selective 5-HT uptake inhibitor with concomitant 5-HT3 receptor antagonist and antiemetic properties |
| Nephrotoxicity | Beta-hexosaminidase (P06865) | Cisplatin increased urinary excretion of LDH (six-fold)@ GGT (twofold)@ and NAG (twofold); CI-973 and carboplatin increased GGT excretion (approximately twofold)@which produced marked nephrotoxicity as determined by biochemical@ functional@ and histopathologic endpoints [ ADR Type 2 ] | Comparative nephrotoxicity of a novel platinum compound, cisplatin, and carboplatin in male |
| Nephrotoxicity | cytochrome P450 (E2RWL6) | Treatment of rats with cisplatin or with cisplatin after chronic pre-exposure to cadmium induced a decrease in kidney cytochrome P-450 and glutathione levels, and in glutathione peroxidase and reductase activities And cadmium nephrotoxicity was characterized by tubular proximal damage with mitochondrial and lysosomal changes and a widespread vesiculation of tubular cells [ ADR Type 1 ] | Cisplatin nephrotoxicity in cadmium-pretreated rats Enzymatic, functional and morphological studies |
| Nephrotoxicity | Gamma-glutamyltranspeptidase (P19440) | Cisplatin increased urinary excretion of LDH (six-fold)@ GGT (twofold)@ and NAG (twofold); CI-973 and carboplatin increased GGT excretion (approximately twofold)@which produced marked nephrotoxicity as determined by biochemical@ functional@ and histopathologic endpoints [ ADR Type 2 ] | Comparative nephrotoxicity of a novel platinum compound, cisplatin, and carboplatin in male |
| Nephrotoxicity | Glutathione peroxidase 1 (P07203) | Treatment of rats with cisplatin or with cisplatin after chronic pre-exposure to cadmium induced a decrease in kidney cytochrome P-450 and glutathione levels@ and in glutathione peroxidase and reductase activities. And cadmium nephrotoxicity was characterized by tubular proximal damage with mitochondrial and lysosomal changes and a widespread vesiculation of tubular cells. [ ADR Type 1 ] | Cisplatin nephrotoxicity in cadmium-pretreated rats Enzymatic, functional and morphological studies |
| Nephrotoxicity | Glutathione s-transferase (P09211) | Glutathione s-transferase (substrate: 1-chloro-2@4-dinitrobenzene) was increased and decreased by cadmium and cisplatin respectively@which leads to cadmium nephrotoxicity was characterized by tubular proximal damage with mitochondrial and lysosomal changes and a widespread vesiculation of tubular cells [ ADR Type 2 ] | Cisplatin nephrotoxicity in cadmium-pretreated rats Enzymatic, functional and morphological studies |
| Nephrotoxicity | L-lactate dehydrogenase (P00338) | Cisplatin increased urinary excretion of LDH (six-fold), GGT (twofold), and NAG (twofold); CI-973 and carboplatin increased GGT excretion (approximately twofold),which produced marked nephrotoxicity as determined by biochemical, functional, and histopathologic endpoints [ ADR Type 2 ] | Comparative nephrotoxicity of a novel platinum compound, cisplatin, and carboplatin in male |
| Nephrotoxicity | N-glucuronyl transferase (I2CQR6) | Enhanced lipid peroxidation, oxidized glutathione and N-glucuronyl transferase activity,which leads to cadmium nephrotoxicity was characterized by tubular proximal damage with mitochondrial and lysosomal changes and a widespread vesiculation of tubular cells. [ ADR Type 2 ] | Cisplatin nephrotoxicity in cadmium-pretreated rats Enzymatic, functional and morphological studies |
| Ototoxicity | Catalase (P04040) | Cisplatin ototoxicity is related to depletion of glutathione and catalase in the cochlea [ ADR Type 2 ] | Application of antioxidants and other agents to prevent cisplatin ototoxicity |
| Ototoxicity | Glutathione peroxidase 1 (P07203) | Cisplatin ototoxicity is related to depletion of glutathione and glutathione peroxidase in the cochlea. [ ADR Type 2 ] | Application of antioxidants and other agents to prevent cisplatin ototoxicity |
| Ototoxicity | Glutathione reductase (P00390) | Cisplatin ototoxicity is related to depletion of glutathione and glutathione reductase in the cochlea [ ADR Type 2 ] | Application of antioxidants and other agents to prevent cisplatin ototoxicity |
| Ototoxicity | Superoxide dismutase (P00441) | Cisplatin ototoxicity is related to depletion of glutathione and superoxide dismutase in the cochlea [ ADR Type 2 ] | Application of antioxidants and other agents to prevent cisplatin ototoxicity |
| Renal Failure | Acyl-coenzyme A oxidase (Q15067) | Cisplatin decreased mRNA levels of peroxisomal acyl-CoA enzyme in mouse kidney and also reduced the mRNA levels and enzyme activities of acyl-CoA and mitochondrial CPT-1 in LLCPK1 cells@which leads to cisplatin-induced acute renal failure. [ ADR Type 1 ] | Alterations of PPARalpha and its coactivator PGC-1 in cisplatin-induced acute renal failure Kidney |
| Renal Failure | Nuclear receptor coactivator 1 (Q15788) | Alterations of PPARalpha and its coactivator receptor-gamma-coactivator-1 (PGC-1) in cisplatin-induced acute renal failure [ ADR Type 3 ] | Alterations of PPARalpha and its coactivator PGC-1 in cisplatin-induced acute renal failure Kidney |
| Renal Failure | Retinoic acid receptor (P19793) | DNA-protein binding studies demonstrated that exposure to cisplatin reduces PPARalpha/retinoid X receptor (RXRalpha) binding activity@which lead to cisplatin-induced acute renal failure. [ ADR Type 1 ] | Alterations of PPARalpha and its coactivator PGC-1 in cisplatin-induced acute renal failure Kidney |
| Tumor Response | Apoptosis regulator Bcl-2 (P10415) | Eleven (32%) and 14 (41%) advanced non-small-cell lung cancer (NSCLC) cases were found positive for DR5 and Bcl-2@ respectively@The response rate was significantly higher in patients with DR5 expression@therefore@Death receptor 5 and Bcl-2 protein expression is as predictors of tumor response [ ADR Type 2 ] | Death receptor 5 and Bcl-2 protein expression as predictors of tumor response to gemcitabine and cisplatin in patients with advanced non-small-cell lung cancer |
| Tumor Response | Tumor necrosis factor receptor superfamily member 10B (O14763) | Eleven (32%) and 14 (41%) advanced non-small-cell lung cancer (NSCLC) cases were found positive for DR5 and Bcl-2, respectively,The response rate was significantly higher in patients with DR5 expression.Therefore,Death receptor 5 and Bcl-2 protein expression is as predictors of tumor response. [ ADR Type 2 ] | Death receptor 5 and Bcl-2 protein expression as predictors of tumor response to gemcitabine and cisplatin in patients with advanced non-small-cell lung cancer |
| Vomiting | 5-hydroxytryptamine 3 receptor (P46098) | Nausea and vomiting associated with the use of 5 HT uptake inhibitors are due to stimulation of 5HT3 receptors. [ ADR Type 1 ] | Litoxetine: a selective 5-HT uptake inhibitor with concomitant 5-HT3 receptor antagonist and antiemetic properties |
This panel provides drug-food interactions and their ADRs along with references
| Food | Toxicity | Reference |
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This panel provides information on metabolites and their ADRs along with references
| Metabolite | Toxicity | Place of Metabolism | Mechanism | Reference |
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This panel provides information on drug category