Details
Stereochemistry | ABSOLUTE |
Molecular Formula | C47H51NO14 |
Molecular Weight | 853.9061 |
Optical Activity | UNSPECIFIED |
Defined Stereocenters | 11 / 11 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
[H][C@@]12C[C@H](O)[C@@]3(C)C(=O)[C@H](OC(C)=O)C4=C(C)[C@H](C[C@@](O)([C@@H](OC(=O)C5=CC=CC=C5)[C@]3([H])[C@@]1(CO2)OC(C)=O)C4(C)C)OC(=O)[C@H](O)[C@@H](NC(=O)C6=CC=CC=C6)C7=CC=CC=C7
InChI
InChIKey=RCINICONZNJXQF-MZXODVADSA-N
InChI=1S/C47H51NO14/c1-25-31(60-43(56)36(52)35(28-16-10-7-11-17-28)48-41(54)29-18-12-8-13-19-29)23-47(57)40(61-42(55)30-20-14-9-15-21-30)38-45(6,32(51)22-33-46(38,24-58-33)62-27(3)50)39(53)37(59-26(2)49)34(25)44(47,4)5/h7-21,31-33,35-38,40,51-52,57H,22-24H2,1-6H3,(H,48,54)/t31-,32-,33+,35-,36+,37+,38-,40-,45+,46-,47+/m0/s1
Molecular Formula | C47H51NO14 |
Molecular Weight | 853.9061 |
Charge | 0 |
Count |
|
Stereochemistry | ABSOLUTE |
Additional Stereochemistry | No |
Defined Stereocenters | 11 / 11 |
E/Z Centers | 0 |
Optical Activity | UNSPECIFIED |
DescriptionSources: http://www.drugbank.ca/drugs/DB01229Curator's Comment: Description was created based on several sources, including http://www.accessdata.fda.gov/drugsatfda_docs/label/2011/020262s049lbl.pdf and https://www.ncbi.nlm.nih.gov/pubmed/18068131
Sources: http://www.drugbank.ca/drugs/DB01229
Curator's Comment: Description was created based on several sources, including http://www.accessdata.fda.gov/drugsatfda_docs/label/2011/020262s049lbl.pdf and https://www.ncbi.nlm.nih.gov/pubmed/18068131
Paclitaxel is a mitotic inhibitor used in cancer chemotherapy. It was discovered in a US National Cancer Institute program at the Research Triangle Institute in 1967 when Monroe E. Wall and Mansukh C. Wani isolated it from the bark of the Pacific yew tree, Taxus brevifolia and named it taxol. Later it was discovered that endophytic fungi in the bark synthesize paclitaxel. When it was developed commercially by Bristol-Myers Squibb (BMS), the generic name was changed to paclitaxel and the BMS compound is sold under the trademark Taxol. In this formulation, paclitaxel is dissolved in Kolliphor EL and ethanol, as a delivery agent. Taxol is marketed for the treatment of Breast cancer; Gastric cancer; Kaposi's sarcoma; Non-small cell lung cancer; Ovarian cancer. A newer formulation, in which paclitaxel is bound to albumin, is sold under the trademark Abraxane. Paclitaxel is a taxoid antineoplastic agent indicated as first-line and subsequent therapy for the treatment of advanced carcinoma of the ovary, and other various cancers including breast cancer. Paclitaxel is a novel antimicrotubule agent that promotes the assembly of microtubules from tubulin dimers and stabilizes microtubules by preventing depolymerization. This stability results in the inhibition of the normal dynamic reorganization of the microtubule network that is essential for vital interphase and mitotic cellular functions. In addition, paclitaxel induces abnormal arrays or "bundles" of microtubules throughout the cell cycle and multiple asters of microtubules during mitosis. Used in the treatment of Kaposi's sarcoma and cancer of the lung, ovarian, and breast. Abraxane® is specfically indicated for the treatment of metastatic breast cancer and locally advanced or metastatic non-small cell lung cancer. Paclitaxel interferes with the normal function of microtubule growth. Whereas drugs like colchicine cause the depolymerization of microtubules in vivo, paclitaxel arrests their function by having the opposite effect; it hyper-stabilizes their structure. This destroys the cell's ability to use its cytoskeleton in a flexible manner. Specifically, paclitaxel binds to the β subunit of tubulin. Tubulin is the "building block" of mictotubules, and the binding of paclitaxel locks these building blocks in place. The resulting microtubule/paclitaxel complex does not have the ability to disassemble. This adversely affects cell function because the shortening and lengthening of microtubules (termed dynamic instability) is necessary for their function as a transportation highway for the cell. Chromosomes, for example, rely upon this property of microtubules during mitosis. Further research has indicated that paclitaxel induces programmed cell death (apoptosis) in cancer cells by binding to an apoptosis stopping protein called Bcl-2 (B-cell leukemia 2) and thus arresting its function.
CNS Activity
Sources: https://www.ncbi.nlm.nih.gov/pubmed/12056715
Curator's Comment: No or negligible penetration of paclitaxel over an intact blood– brain barrier
Originator
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: HeLa cell growth Sources: https://www.ncbi.nlm.nih.gov/pubmed/27095936 |
7.08 µM [IC50] | ||
Target ID: SKOV3 breast cancer cell growth Sources: https://www.ncbi.nlm.nih.gov/pubmed/27599579 |
38.7 nM [IC50] | ||
Target ID: GO:0046785 Sources: https://www.ncbi.nlm.nih.gov/pubmed/8555181 |
23.0 µM [EC50] | ||
Target ID: CHEMBL1915 Sources: http://www.drugbank.ca/drugs/DB01229 |
|||
Target ID: CHEMBL4860 Sources: http://www.drugbank.ca/drugs/DB01229 |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Primary | TAXOL Approved UseTAXOL is indicated as first-line and subsequent therapy for the treatment of advanced carcinoma of the ovary. Launch Date1998 |
|||
Primary | TAXOL Approved UseTAXOL is indicated for the treatment of breast cancer after failure of combination chemotherapy for metastatic disease or relapse within 6 months of adjuvant chemotherapy. Launch Date1998 |
|||
Primary | TAXOL Approved UseTAXOL, in combination with cisplatin, is indicated for the first-line treatment of nonsmall cell lung cancer in patients who are not candidates for potentially curative surgery and/or radiation therapy. Launch Date1998 |
Cmax
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
6.92 μM EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/8664192 |
250 mg/m² steady-state, intravenous dose: 250 mg/m² route of administration: Intravenous experiment type: STEADY-STATE co-administered: |
PACLITAXEL plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
0.5 μM EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/7799018 |
175 mg/m² steady-state, intravenous dose: 175 mg/m² route of administration: Intravenous experiment type: STEADY-STATE co-administered: |
PACLITAXEL plasma | Homo sapiens population: UNKNOWN age: ADULT sex: FEMALE food status: UNKNOWN |
AUC
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
27.07 μM × h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/8664192 |
250 mg/m² steady-state, intravenous dose: 250 mg/m² route of administration: Intravenous experiment type: STEADY-STATE co-administered: |
PACLITAXEL plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
T1/2
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
14.8 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/7799018 |
175 mg/m² steady-state, intravenous dose: 175 mg/m² route of administration: Intravenous experiment type: STEADY-STATE co-administered: |
PACLITAXEL plasma | Homo sapiens population: UNKNOWN age: ADULT sex: FEMALE food status: UNKNOWN |
Funbound
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
6.5% |
PACLITAXEL plasma | Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN |
Doses
Dose | Population | Adverse events |
---|---|---|
135 mg/m2 1 times / 3 weeks multiple, intravenous Recommended Dose: 135 mg/m2, 1 times / 3 weeks Route: intravenous Route: multiple Dose: 135 mg/m2, 1 times / 3 weeks Sources: |
unhealthy, adult Health Status: unhealthy Age Group: adult Sources: |
Other AEs: Anaphylaxis, Dyspnea... Other AEs: Anaphylaxis (2%) Sources: Dyspnea (severe, 2%) Hypotension (severe, 2%) Generalized urticaria (severe, 2%) Angioedema (severe, 2%) |
AEs
AE | Significance | Dose | Population |
---|---|---|---|
Anaphylaxis | 2% | 135 mg/m2 1 times / 3 weeks multiple, intravenous Recommended Dose: 135 mg/m2, 1 times / 3 weeks Route: intravenous Route: multiple Dose: 135 mg/m2, 1 times / 3 weeks Sources: |
unhealthy, adult Health Status: unhealthy Age Group: adult Sources: |
Angioedema | severe, 2% | 135 mg/m2 1 times / 3 weeks multiple, intravenous Recommended Dose: 135 mg/m2, 1 times / 3 weeks Route: intravenous Route: multiple Dose: 135 mg/m2, 1 times / 3 weeks Sources: |
unhealthy, adult Health Status: unhealthy Age Group: adult Sources: |
Dyspnea | severe, 2% | 135 mg/m2 1 times / 3 weeks multiple, intravenous Recommended Dose: 135 mg/m2, 1 times / 3 weeks Route: intravenous Route: multiple Dose: 135 mg/m2, 1 times / 3 weeks Sources: |
unhealthy, adult Health Status: unhealthy Age Group: adult Sources: |
Generalized urticaria | severe, 2% | 135 mg/m2 1 times / 3 weeks multiple, intravenous Recommended Dose: 135 mg/m2, 1 times / 3 weeks Route: intravenous Route: multiple Dose: 135 mg/m2, 1 times / 3 weeks Sources: |
unhealthy, adult Health Status: unhealthy Age Group: adult Sources: |
Hypotension | severe, 2% | 135 mg/m2 1 times / 3 weeks multiple, intravenous Recommended Dose: 135 mg/m2, 1 times / 3 weeks Route: intravenous Route: multiple Dose: 135 mg/m2, 1 times / 3 weeks Sources: |
unhealthy, adult Health Status: unhealthy Age Group: adult Sources: |
Overview
CYP3A4 | CYP2C9 | CYP2D6 | hERG |
---|---|---|---|
OverviewOther
Other Inhibitor | Other Substrate | Other Inducer |
---|---|---|
Drug as perpetrator
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
Sources: https://www.jci.org/articles/view/15451 Page: - |
no |
Drug as victim
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2005/21660_ABRAXANE_biopharmr.PDF#page=20 Page: 20.0 |
major | |||
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2005/21660_ABRAXANE_biopharmr.PDF#page=20 Page: 20.0 |
minor | |||
Page: - |
no | |||
Page: - |
yes [Km 6.79 uM] | |||
Page: - |
yes | |||
Sources: https://www.nature.com/articles/tpj201013 Page: - |
yes | |||
Sources: https://www.jci.org/articles/view/96160 Page: - |
yes | |||
Page: - |
yes |
PubMed
Title | Date | PubMed |
---|---|---|
Dissecting cellular processes using small molecules: identification of colchicine-like, taxol-like and other small molecules that perturb mitosis. | 2000 Apr |
|
Paclitaxel in advanced non-small cell lung cancer : an alternative high-dose weekly schedule. | 2000 Apr |
|
Paclitaxel-induced apoptosis in non-small cell lung cancer cell lines is associated with increased caspase-3 activity. | 2000 Apr |
|
Microtubules, but not actin filaments, drive daughter cell budding and cell division in Toxoplasma gondii. | 2000 Apr |
|
Schedule dependency of paclitaxel-induced neuropathy in mice: a morphological study. | 2000 Aug |
|
Phase I study of paclitaxel and day 1/day 8 gemcitabine in patients with solid malignancies. | 2000 Aug |
|
Phase II clinical trials of cisplatin-then-paclitaxel and paclitaxel-then-cisplatin in patients with previously untreated advanced epithelial ovarian cancer. | 2000 Dec |
|
Evidence for a schedule-dependent deleterious interaction between paclitaxel, vinblastine and cisplatin (PVC) in the treatment of advanced transitional cell carcinoma. | 2000 Dec |
|
Paclitaxel-induced stomal neuropathy: a unique cause of pain in a patient with ileal conduit. | 2000 Dec 20 |
|
Mouse toll-like receptor 4.MD-2 complex mediates lipopolysaccharide-mimetic signal transduction by Taxol. | 2000 Jan 28 |
|
Slow polymerization of Mycobacterium tuberculosis FtsZ. | 2000 Jul |
|
Polymeric micellar paclitaxel phosphorylates Bcl-2 and induces apoptotic regression of androgen-independent LNCaP prostate tumors. | 2000 Jul 1 |
|
Mechanism of paclitaxel activity in Kaposi's sarcoma. | 2000 Jul 1 |
|
Susceptibility to drug-induced apoptosis correlates with differential modulation of Bad, Bcl-2 and Bcl-xL protein levels. | 2000 Jun |
|
Biochemical mechanism of cross-resistance to paclitaxel in a mitomycin c-resistant human bladder cancer cell line. | 2000 Mar 31 |
|
Cardiac sequelae of doxorubicin and paclitaxel as induction chemotherapy prior to high-dose chemotherapy and peripheral blood progenitor cell transplantation in women with high-risk primary or metastatic breast cancer. | 2000 May |
|
Phase II study of 3-hour infusion of high dose paclitaxel in refractory and relapsed aggressive non-Hodgkin's lymphomas. Groupe d'Etude des Lymphomes de l'Adulte. | 2000 May |
|
Second-line chemotherapy with paclitaxel, cisplatin and gemcitabine in pre-treated sensitive cisplatin-based patients with advanced non-small cell lung cancer. | 2000 May-Jun |
|
Cell cycle status and apoptosis of hematopoietic progenitor cells released into the peripheral blood after taxanes and granulocyte colony-stimulating factor in breast cancer patients. | 2000 May-Jun |
|
Bilateral blindness and lumbosacral myelopathy associated with high-dose carmustine and cisplatin therapy. | 2000 Sep |
|
Comparison of 2-methoxyestradiol-induced, docetaxel-induced, and paclitaxel-induced apoptosis in hepatoma cells and its correlation with reactive oxygen species. | 2000 Sep 1 |
|
Doxorubicin and paclitaxel in the treatment of advanced breast cancer: efficacy and cardiac considerations. | 2001 |
|
The pharmacokinetics and pharmacodynamics of high-dose paclitaxel monotherapy (825 mg/m2 continuous infusion over 24 h) with hematopoietic support in women with metastatic breast cancer. | 2001 |
|
Management of recurrent juvenile granulosa cell tumor of the ovary. | 2001 Apr |
|
Recurrent metastatic fallopian tube carcinoma in pregnancy. | 2001 Apr |
|
Peroxisome proliferator-activated receptor gamma ligands suppress the transcriptional activation of cyclooxygenase-2. Evidence for involvement of activator protein-1 and CREB-binding protein/p300. | 2001 Apr 13 |
|
Regional drug delivery with radiation for the treatment of Ewing's sarcoma. In vitro development of a taxol release system. | 2001 Apr 2 |
|
Taxol-induced cell cycle arrest and apoptosis: dose-response relationship in lung cancer cells of different wild-type p53 status and under isogenic condition. | 2001 Apr 26 |
|
Gemcitabine, paclitaxel, and trastuzumab in metastatic breast cancer. | 2001 Feb |
|
Phytochemistry and medicinal plants. | 2001 Feb |
|
Isolation of cortical MTs from tobacco BY-2 cells. | 2001 Feb |
|
Study of multi-drug resistant mechanisms in a taxol-resistant hepatocellular carcinoma QGY-TR 50 cell line. | 2001 Feb 9 |
|
Phase I study of paclitaxel (Taxol) plus vinorelbine (Navelbine) in patients with untreated stage IIIb and IV non-small cell lung cancer. | 2001 Feb-Mar |
|
Treatment of non-small-cell lung cancer in North America: the emerging role of irinotecan. | 2001 Jan |
|
Neurotoxicity associated with a regimen of carboplatin (AUC 5-6) and paclitaxel (175 mg/m2 over 3 h) employed in the treatment of gynecologic malignancies. | 2001 Jan |
|
Receptor-mediated cell modulator delivery to hepatocyte using nanoparticles coated with carbohydrate-carrying polymers. | 2001 Jan |
|
Cutting edge: Gln22 of mouse MD-2 is essential for species-specific lipopolysaccharide mimetic action of taxol. | 2001 Jan 1 |
|
Pretreatment with paclitaxel enhances apo-2 ligand/tumor necrosis factor-related apoptosis-inducing ligand-induced apoptosis of prostate cancer cells by inducing death receptors 4 and 5 protein levels. | 2001 Jan 15 |
|
Taxane-antibody conjugates afford potent cytotoxicity, enhanced solubility, and tumor target selectivity. | 2001 Jan 15 |
|
Antitumor synergy of CV787, a prostate cancer-specific adenovirus, and paclitaxel and docetaxel. | 2001 Jan 15 |
|
Dispersion of cyclin B mRNA aggregation is coupled with translational activation of the mRNA during zebrafish oocyte maturation. | 2001 Jan 15 |
|
Increased p53 phosphorylation after microtubule disruption is mediated in a microtubule inhibitor- and cell-specific manner. | 2001 Jan 4 |
|
Enhanced taxol production and release in Taxus chinensis cell suspension cultures with selected organic solvents and sucrose feeding. | 2001 Jan-Feb |
|
The role of actin filaments and microtubules in hepatocyte spheroid self-assembly. | 2001 Mar |
|
Phase II trial of paclitaxel and carboplatin in metastatic small-cell lung cancer: a Groupe Français de Pneumo-Cancérologie study. | 2001 Mar 1 |
|
Activation of caspase-8 in drug-induced apoptosis of B-lymphoid cells is independent of CD95/Fas receptor-ligand interaction and occurs downstream of caspase-3. | 2001 Mar 1 |
|
Paclitaxel sensitization of multidrug-resistant cells to chemotherapy is independent of the cell cycle. | 2001 Mar 1 |
|
Regulation of ROMK1 channels by protein-tyrosine kinase and -tyrosine phosphatase. | 2001 Mar 9 |
|
Inhibition of telomerase activity as a measure of tumor cell killing by cisplatin in squamous cell carcinoma cell line. | 2001 Mar-Apr |
|
Regulation of stress-responsive mitogen-activated protein (MAP) kinase pathways by TAO2. | 2001 May 11 |
Patents
Sample Use Guides
For previously untreated patients with carcinoma of the ovary, one of the following recommended regimens may be given every 3 weeks.
a.TAXOL (PACLITAXEL) administered intravenously over 3 hours at a dose of 175 mg/m2 followed by cisplatin at a dose of 75 mg/m2; or
b.TAXOL (PACLITAXEL) administered intravenously over 24 hours at a dose of 135 mg/m2 followed by cisplatin at a dose of 75 mg/m2
2) In patients previously treated with chemotherapy for carcinoma of the ovary, the recommended regimen is TAXOL (PACLITAXEL) 135 mg/m2 or 175 mg/m2 administered intravenously over 3 hours every 3 weeks.
Route of Administration:
Intravenous
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/27420038
Paclitaxel inhibited tubulin polymerization in the presence of MAPs in vitro with an IC50 value of 38.19 ± 3.33 uM in living cancer cells (Hela cells and human osteosarcoma U2OS cells).
Substance Class |
Chemical
Created
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Edited
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Record UNII |
3PPC5TL76P
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Record Status |
Validated (UNII)
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Record Version |
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