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Details

Stereochemistry EPIMERIC
Molecular Formula C51H57NO18
Molecular Weight 971.9942
Optical Activity UNSPECIFIED
Defined Stereocenters 11 / 12
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of PACLITAXEL CERIBATE

SMILES

[H][C@@]12C[C@H](OC(=O)OCC(O)CO)[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=HSUDWURBWSUCOB-JPHWUADUSA-N
InChI=1S/C51H57NO18/c1-27-34(67-46(61)39(57)38(30-16-10-7-11-17-30)52-44(59)31-18-12-8-13-19-31)23-51(63)43(69-45(60)32-20-14-9-15-21-32)41-49(6,42(58)40(66-28(2)54)37(27)48(51,4)5)35(68-47(62)64-25-33(56)24-53)22-36-50(41,26-65-36)70-29(3)55/h7-21,33-36,38-41,43,53,56-57,63H,22-26H2,1-6H3,(H,52,59)/t33?,34-,35-,36+,38-,39+,40+,41-,43-,49+,50-,51+/m0/s1

HIDE SMILES / InChI

Molecular Formula C51H57NO18
Molecular Weight 971.9942
Charge 0
Count
Stereochemistry EPIMERIC
Additional Stereochemistry No
Defined Stereocenters 10 / 12
E/Z Centers 0
Optical Activity UNSPECIFIED

Description
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

Curator's Comment: No or negligible penetration of paclitaxel over an intact blood– brain barrier

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
7.08 µM [IC50]
Target ID: SKOV3 breast cancer cell growth
38.7 nM [IC50]
23.0 µM [EC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
TAXOL

Approved Use

TAXOL is indicated as first-line and subsequent therapy for the treatment of advanced carcinoma of the ovary.

Launch Date

1998
Primary
TAXOL

Approved Use

TAXOL 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 Date

1998
Primary
TAXOL

Approved Use

TAXOL, 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 Date

1998
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
6.92 μM
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
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

AUC

ValueDoseCo-administeredAnalytePopulation
27.07 μM × h
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

T1/2

ValueDoseCo-administeredAnalytePopulation
14.8 h
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

Funbound

ValueDoseCo-administeredAnalytePopulation
6.5%
PACLITAXEL plasma
Homo sapiens
population: UNKNOWN
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse 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
Other AEs: Anaphylaxis, Dyspnea...
Other AEs:
Anaphylaxis (2%)
Dyspnea (severe, 2%)
Hypotension (severe, 2%)
Generalized urticaria (severe, 2%)
Angioedema (severe, 2%)
Sources:
AEs

AEs

AESignificanceDosePopulation
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
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
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
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
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
PubMed

PubMed

TitleDatePubMed
Phase II clinical trials of cisplatin-then-paclitaxel and paclitaxel-then-cisplatin in patients with previously untreated advanced epithelial ovarian cancer.
2000 Dec
A paclitaxel-containing chemotherapy does not cause central nervous adverse effects: a prospective study in patients with ovarian cancer.
2000 Sep-Oct
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
Drug approval summaries: arsenic trioxide, tamoxifen citrate, anastrazole, paclitaxel, bexarotene.
2001
High affinity binding of paclitaxel to human serum albumin.
2001 Apr
Management of recurrent juvenile granulosa cell tumor of the ovary.
2001 Apr
Recurrent metastatic fallopian tube carcinoma in pregnancy.
2001 Apr
HPV16-E6 enhances mitoxantrone sensitivity in a human ovarian cancer line: an isolated instance or a trend?
2001 Apr
Cell cycle-related changes in regulatory volume decrease and volume-sensitive chloride conductance in mouse fibroblasts.
2001 Apr
Connexin 43 (cx43) enhances chemotherapy-induced apoptosis in human glioblastoma cells.
2001 Apr 1
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
Biweekly gemcitabine, doxorubicin, and paclitaxel as first-line treatment in metastatic breast cancer. Final results from a phase II trial.
2001 Feb
Gemcitabine, paclitaxel, and trastuzumab in metastatic breast cancer.
2001 Feb
Gemcitabine plus cisplatin in breast cancer.
2001 Feb
Phytochemistry and medicinal plants.
2001 Feb
Membrane macrophage colony-stimulating factor on MADB106 breast cancer cells does not activate cytotoxic macrophages but immunizes rats against breast cancer.
2001 Feb
Isolation of cortical MTs from tobacco BY-2 cells.
2001 Feb
Selective drug resistant human osteosarcoma cell lines.
2001 Feb
Changes in glycosylation during Drosophila development. The influence of ecdysone on hemomucin isoforms.
2001 Feb
Disruption of microtubular cytoskeleton induced by cryptogein, an elicitor of hypersensitive response in tobacco cells.
2001 Feb
Involvement of Asp-Glu-Val-Asp-directed, caspase-mediated mitogen-activated protein kinase kinase 1 Cleavage, c-Jun N-terminal kinase activation, and subsequent Bcl-2 phosphorylation for paclitaxel-induced apoptosis in HL-60 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
Cisplatin and vinorelbine as second-line chemotherapy in patients with advanced non-small cell lung cancer (NSCLC) resistant to taxol plus gemcitabine.
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
Tumor cell-derived TGF-beta and IL-10 dysregulate paclitaxel-induced macrophage activation.
2001 Jan
Colchicine and griseofulvin inhibit VCAM-1 expression on human vascular endothelial cells - evidence for the association of VCAM-1 expression with microtubules.
2001 Jan
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
Stimulation of taxol production and excretion in Taxus spp cell cultures by rare earth chemical lanthanum.
2001 Jan 23
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
Dynamic events are differently mediated by microfilaments, microtubules, and mitogen-activated protein kinase during porcine oocyte maturation and fertilization in vitro.
2001 Mar
Effects of stathmin inhibition on the mitotic spindle.
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
Effects of emulsifiers on the controlled release of paclitaxel (Taxol) from nanospheres of biodegradable polymers.
2001 Mar 12
Paclitaxel restores radiation-induced apoptosis in a bcl-2-expressing, radiation-resistant lymphoma cell line.
2001 Mar 15
Insulin-like growth factor-I receptor antagonism results in increased cytotoxicity of breast cancer cells to doxorubicin and taxol.
2001 Mar-Apr
Inhibition of telomerase activity as a measure of tumor cell killing by cisplatin in squamous cell carcinoma cell line.
2001 Mar-Apr
P-glycoprotein efflux pump expression and activity in Calu-3 cells.
2001 May
Regulation of stress-responsive mitogen-activated protein (MAP) kinase pathways by TAO2.
2001 May 11
Regulation of BRCA1 and BRCA2 transcript in response to cisplatin, adriamycin, taxol and ionising radiation is correlated to p53 functional status in ovarian cancer cell lines.
2001 May-Jun
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
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
by admin
on Fri Dec 15 18:53:47 GMT 2023
Edited
by admin
on Fri Dec 15 18:53:47 GMT 2023
Record UNII
B3C86E80A0
Record Status Validated (UNII)
Record Version
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Name Type Language
PACLITAXEL CERIBATE
INN  
INN  
Official Name English
PROTAXEL
Brand Name English
BP-179
Code English
7.BETA.-((2RS)-2,3-DIHYDROXYPROPOXYCARBONYLOXY)-1-HYDROXY-9-OXO-5.BETA.,20-EPOXYTAX-11-ENE-2.ALPHA.,4,10.BETA.,13.ALPHA.-TETRAYL 4,10-DIACETATE 2-BENZOATE 13-((2R,3S)-3-BENZAMIDO-2-HYDROXY-3-PHENYLPROPANOATE)
Common Name English
paclitaxel ceribate [INN]
Common Name English
Classification Tree Code System Code
NCI_THESAURUS C1490
Created by admin on Fri Dec 15 18:53:47 GMT 2023 , Edited by admin on Fri Dec 15 18:53:47 GMT 2023
FDA ORPHAN DRUG 168203
Created by admin on Fri Dec 15 18:53:47 GMT 2023 , Edited by admin on Fri Dec 15 18:53:47 GMT 2023
NCI_THESAURUS C67437
Created by admin on Fri Dec 15 18:53:47 GMT 2023 , Edited by admin on Fri Dec 15 18:53:47 GMT 2023
Code System Code Type Description
CAS
186040-50-6
Created by admin on Fri Dec 15 18:53:47 GMT 2023 , Edited by admin on Fri Dec 15 18:53:47 GMT 2023
PRIMARY
ChEMBL
CHEMBL2107766
Created by admin on Fri Dec 15 18:53:47 GMT 2023 , Edited by admin on Fri Dec 15 18:53:47 GMT 2023
PRIMARY
SMS_ID
300000034323
Created by admin on Fri Dec 15 18:53:47 GMT 2023 , Edited by admin on Fri Dec 15 18:53:47 GMT 2023
PRIMARY
EPA CompTox
DTXSID801318715
Created by admin on Fri Dec 15 18:53:47 GMT 2023 , Edited by admin on Fri Dec 15 18:53:47 GMT 2023
PRIMARY
INN
8294
Created by admin on Fri Dec 15 18:53:47 GMT 2023 , Edited by admin on Fri Dec 15 18:53:47 GMT 2023
PRIMARY
MESH
C434865
Created by admin on Fri Dec 15 18:53:47 GMT 2023 , Edited by admin on Fri Dec 15 18:53:47 GMT 2023
PRIMARY
NCI_THESAURUS
C96934
Created by admin on Fri Dec 15 18:53:47 GMT 2023 , Edited by admin on Fri Dec 15 18:53:47 GMT 2023
PRIMARY
PUBCHEM
390521
Created by admin on Fri Dec 15 18:53:47 GMT 2023 , Edited by admin on Fri Dec 15 18:53:47 GMT 2023
PRIMARY
FDA UNII
B3C86E80A0
Created by admin on Fri Dec 15 18:53:47 GMT 2023 , Edited by admin on Fri Dec 15 18:53:47 GMT 2023
PRIMARY
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