| Drug Name: | Paclitaxel (33069-62-4) |
|---|---|
| PubChem ID: | 122361554 |
| SMILES: | CC1=C2[C@H](C(=O)[C@@]3([C@H](C[C@@H]4[C@](C3C([C@@](C2(C)C)(C[C@@H]1OC(=O)[C@H]([C@H](C5=CC=CC=C5)NC(=O)C6=CC=CC=C6)O)O)OC(=O)C7=CC=CC=C7)(CO4)OC(=O)C)O)C)OC(=O)C |
| InchiKey: | RCINICONZNJXQF-VLZOSYTRSA-N |
| Therapeutic Category: | Antimitotic Agents, Antineoplastic Agents, Mitosis Modulators, Tubulin Modulators |
| Molecular Weight (dalton) | : | 853.918 |
| LogP | : | 3.7357 |
| Ring Count | : | 3 |
| Hydrogen Bond Acceptor Count | : | 14 |
| Hydrogen Bond Donor Count | : | 4 |
| Total Polar Surface Area | : | 221.29 |
This panel provides information on interacting drugs and their ADRs along with references
| Interacting drug | Toxicity | Interaction Type | Mechanism | Reference |
|---|---|---|---|---|
| Doxorubicin (23214-92-8) | Cardiotoxicity | Synergistic | in vitro studies in human myocardium showed that paclitaxel increased the conversion of doxorubicin to doxorubicinol, the metabolite that is thought to be responsible for cardiotoxicity. | Neurological symptoms and coma associated with doxorubicin administration during chronic cyclosporin therapy |
| Lopinavir (192725-17-0) | Myelosuppression | Synergistic | Paclitaxel is metabolised by the cytochrome P450 enzymes CYP2C8 and CYP3A4.indinavir are known to inhibit CYP3A4 enzyme | Recrudescent Kaposi's Sarcoma After Initiation of HAART: A Manifestation of Immune Reconstitution Syndrome |
| Ifosfamide (3778-73-2) | Cell-Mediated Cytotoxicity | Synergistic | unknown | cIfosfamide-based drug combinations: preclinical evaluation of drug interactions and translation into the clin |
This panel provides drug-protein interaction and their ADRs along with references
| Toxicity | Interacting Protein | Mechanism | Reference |
|---|---|---|---|
| Apoptosis | Baculoviral IAP repeat-containing protein (Q13490) | Paclitaxel-induced apoptosis of breast cancer cells Constitutive activation of NF-kappaB leads to overexpression of the anti-apoptotic genes c-inhibitor of apoptosis 2 (c-IAP2) and manganese superoxide dismutase (Mn-SOD) in breast cancer cells [ ADR Type 2 ] | Paclitaxel sensitivity of breast cancer cells with constitutively active NF-kappaB is enhanced by IkappaBalpha super-repressor |
| Apoptosis | Bcl2-antaGOnist of cell death (Q92934) | Overexpression of Bcl-xL blocked various aspects of paclitaxel-mediated apoptosis@ including caspase-3 activation@ degradation of poly(ADP-ribose) polymerase (PARP)@ loss of mitochondrial membrane potential (Delta Psim)@ and release of cytochrome c. [ ADR Type 2 ] | Bryostatin 1 enhances paclitaxel-induced mitochondrial dysfunction and apoptosis in human leukemia cells (U937) ectopically expressing Bcl-xL Leukemia |
| Apoptosis | c-Mos (Q71MU8) | Tubulin-disturbing agents induce c-Mos gene expression and activation in SKOV3 ovarian carcinoma cells and that such an effect occurs after mitotic blockade and coincides with drug-induced apoptosis | Paclitaxel-induced apoptosis is associated with expression and activation of c-Mos gene product in human ovarian carcinoma SKOV3 cells |
| Apoptosis | Cell cycle-related kinase (Q8IZL9) | Expression of CDK4 seems to make the cells more sensitive to paclitaxel-induced apoptosis [ ADR Type 2 ] | CDK4 down-regulation induced by paclitaxel is associated with G1 arrest in gastric cancer cells |
| Apoptosis | Defender against cell death 1 (P61803) | Paclitaxel-induced apoptosis of breast cancer cells.Expression of the anti-apoptotic tumor necrosis factor receptor associated factor 1 (TRAF1) and defender-against cell death (DAD-1) is regulated by NF-kappaB in certain breast cancer cells. [ ADR Type 2 ] | Paclitaxel sensitivity of breast cancer cells with constitutively active NF-kappaB is enhanced by IkappaBalpha super-repressor |
| Apoptosis | Glutathione s-transferase (P09211) | Apoptosis [ ADR Type 2 ] | Paclitaxel-induced apoptosis is associated with expression and activation of c-Mos gene product in human ovarian carcinoma SKOV3 cells |
| Apoptosis | Manganese-containing superoxide dismutase (Mn-SOD) (Q4ZJI1) | Paclitaxel-induced apoptosis of breast cancer cells. Constitutive activation of NF-kappaB leads to overexpression of the anti-apoptotic genes c-inhibitor of apoptosis 2 (c-IAP2) and manganese superoxide dismutase (Mn-SOD) in breast cancer cells. [ ADR Type 2 ] | Paclitaxel sensitivity of breast cancer cells with constitutively active NF-kappaB is enhanced by IkappaBalpha super-repressor |
| Apoptosis | Mitogen-activated protein kinase(ERK) (P28482) | Bcl-2 phosphorylation is tightly associated with mitotic arrest and fail to demonstrate that it is a determinant of progression into apoptosis after mitotic arrest induced by anti-tubulin agents. [ ADR Type 2 ] | Paclitaxel-induced apoptosis is associated with expression and activation of c-Mos gene product in human ovarian carcinoma SKOV3 cells |
| Apoptosis | Nuclear factor NF-kappa-B (P19838) | Paclitaxel-induced G2/M cell cycle arrest;NF-kappaB-inducible genes protect cancer cells against paclitaxel as MDA-MB-231 breast cancer cells modified to overexpress IkappaBalpha required lower concentrations of paclitaxel to arrest at the G2/M phase of the cell cycle and underGO apoptosis when compared to parental cells [ ADR Type 2 ] | Paclitaxel sensitivity of breast cancer cells with constitutively active NF-kappaB is enhanced by IkappaBalpha super-repressor |
| Apoptosis | Poly [ADP-ribose] polymerase (Q9ZP54) | Overexpression of Bcl-xL blocked various aspects of paclitaxel-mediated apoptosis by caspase-3 activation. [ ADR Type 2 ] | Bryostatin 1 enhances paclitaxel-induced mitochondrial dysfunction and apoptosis in human leukemia cells (U937) ectopically expressing Bcl-xL Leukemia |
| Apoptosis Of Breast Cancer Cells | c-inhibitor of apoptosis 2 (c-IAP2) (P00008) | Constitutive activation of NF-kappaB leads to overexpression of the anti-apoptotic genes c-inhibitor of apoptosis 2 (c-IAP2) and manganese superoxide dismutase (Mn-SOD) in breast cancer cells,which increase paclitaxel-induced apoptosis of breast cancer cells. [ ADR Type 2 ] | Paclitaxel sensitivity of breast cancer cells with constitutively active NF-kappaB is enhanced by IkappaBalpha super-repressor |
| Apoptosis Of Breast Cancer Cells | Defender against cell death 1 (P61803) | Expression of the anti-apoptotic tumor necrosis factor receptor associated factor 1 (TRAF1) and defender-against cell death (DAD-1) is regulated by NF-kappaB in certain breast cancer cells@which increases paclitaxel-induced apoptosis of breast cancer cells. [ ADR Type 2 ] | Paclitaxel sensitivity of breast cancer cells with constitutively active NF-kappaB is enhanced by IkappaBalpha super-repressor |
| Apoptosis Of Breast Cancer Cells | Manganese-containing superoxide dismutase (Mn-SOD) (Q4ZJI1) | Constitutive activation of NF-kappaB leads to overexpression of the anti-apoptotic genes c-inhibitor of apoptosis 2 (c-IAP2) and manganese superoxide dismutase (Mn-SOD) in breast cancer cells@which increase paclitaxel-induced apoptosis of breast cancer cells [ ADR Type 2 ] | Paclitaxel sensitivity of breast cancer cells with constitutively active NF-kappaB is enhanced by IkappaBalpha super-repressor |
| Apoptosis Of Breast Cancer Cells | Nuclear factor NF-kappa-B (P19838) | Constitutive activation of NF-kappaB leads to overexpression of the anti-apoptotic genes c-inhibitor of apoptosis 2 (c-IAP2) and manganese superoxide dismutase (Mn-SOD) in breast cancer cells@which increase paclitaxel-induced apoptosis of breast cancer cells. [ ADR Type 2 ] | Paclitaxel sensitivity of breast cancer cells with constitutively active NF-kappaB is enhanced by IkappaBalpha super-repressor |
| Apoptosis Of Breast Cancer Cells | TNF receptor-associated factor 1 (Q13077) | Expression of the anti-apoptotic tumor necrosis factor receptor associated factor 1 (TRAF1) and defender-against cell death (DAD-1) is regulated by NF-kappaB in certain breast cancer cells@which increases paclitaxel-induced apoptosis of breast cancer cells. [ ADR Type 2 ] | Paclitaxel sensitivity of breast cancer cells with constitutively active NF-kappaB is enhanced by IkappaBalpha super-repressor |
| Cell Cycle Arrest | Cell cycle-related kinase (Q8IZL9) | Paclitaxel-induced CDK4 down-regulation resulted in a cell cycle arrest at G1-S phase [ ADR Type 2 ] | CDK4 down-regulation induced by paclitaxel is associated with G1 arrest in gastric cancer cells |
| Cytotoxicity | Multidrug resistance protein 1 (P08183) | Inhibition of P-glycoprotein (PGP) activity by verapamil or PSC 833 enhances the Cytotoxicity of vincristine@ doxorubicin@ teniposide and taxol [ ADR Type 4 ] | P-glycoprotein and multidrug resistance-associated protein mediate specific patterns of multidrug resistance in malignant glioma cell lines, but not in primary glioma cells |
| Mitochondrial Defects | Poly [ADP-ribose] polymerase (Q9ZP54) | Overexpression of Bcl-xL blocked various aspects of paclitaxel-mediated mitochondrial dysfunction by degradation of poly(ADP-ribose) polymerase (PARP) [ ADR Type 2 ] | Bryostatin 1 enhances paclitaxel-induced mitochondrial dysfunction and apoptosis in human leukemia cells (U937) ectopically expressing Bcl-xL Leukemia |
| Mitotic Catastrophe | Serine/threonine-protein kinase PLK2 (Q9NYY3) | Silencing of the novel p53 target gene serum inducible kinase (Snk/Plk2) leads to mitotic catastrophe in paclitaxel (taxol)-exposed cells. [ ADR Type 2 ] | Silencing of the novel p53 target gene Snk/Plk2 leads to mitotic catastrophe in paclitaxel (taxol)-exposed cells |
| Mitotic Catastrophe | wild-type p53 (P04637) | Silencing of the novel p53 target gene serum inducible kinase (Snk/Plk2) leads to mitotic catastrophe in paclitaxel (taxol)-exposed cells [ ADR Type 2 ] | Silencing of the novel p53 target gene Snk/Plk2 leads to mitotic catastrophe in paclitaxel (taxol)-exposed cells |
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 |
|---|
This panel provides information on drug category