(1S,2S,4S,7R,9S,10S,12R,15S)-4,12-bis(acetyloxy)-1,9-dihydroxy-15-{[(2R,3S)-2-hydroxy-3-phenyl-3-(phenylformamido)propanoyl]oxy}-10,14,17,17-tetramethyl-11-oxo-6-oxatetracyclo[11.3.1.0^{3,10}.0^{4,7}]heptadec-13-en-2-yl benzoate

• ChemBase ID: 72546
• Molecular Formular: C47H51NO14
• Molecular Mass: 853.90614
• Monoisotopic Mass: 853.33095532
• SMILES: c1cccc(c1)C(=O)N[C@H]([C@H](C(=O)O[C@H]1C[C@@]2(C(C(=C1C)[C@H](C(=O)[C@]1(C([C@]3([C@@H](C[C@@H]1O)OC3)OC(=O)C)[C@@H]2OC(=O)c1ccccc1)C)OC(=O)C)(C)C)O)O)c1ccccc1
• Canonical SMILES: CC(=O)O[C@H]1C(=O)[C@]2(C)[C@@H](O)C[C@@H]3[C@](C2[C@@H]([C@]2(C(C1=C(C)[C@@H](OC(=O)[C@@H]([C@H](c1ccccc1)NC(=O)c1ccccc1)O)C2)(C)C)O)OC(=O)c1ccccc1)(CO3)OC(=O)C
• InChI: 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
• InChIKey: RCINICONZNJXQF-VAZQATRQSA-N

NAMES AND DATABASE IDS

Names

• IUPAC name: (1S,2S,4S,7R,9S,10S,12R,15S)-4,12-bis(acetyloxy)-1,9-dihydroxy-15-{[(2R,3S)-2-hydroxy-3-phenyl-3-(phenylformamido)propanoyl]oxy}-10,14,17,17-tetramethyl-11-oxo-6-oxatetracyclo[11.3.1.0^{3,10}.0^{4,7}]heptadec-13-en-2-yl benzoate
• IUPAC Traditional name: @paclitaxel
• Synonyms: Onxol; Taxol; Nov-Onxol; Paclitaxel(Taxol)

Database IDs

• CAS Number: 33069-62-4
• PubChem SID: 162037471
• PubChem CID: 441276

CALCULATED PROPERTIES

• H Acceptors: 10
• H Donor: 4
• LogD (pH = 5.5): 3.5388339
• LogD (pH = 7.4): 3.538369
• Log P: 3.53884
• Molar Refractivity: 218.2945 cm^3
• Polarizability: 86.54275 Å^3
• Polar Surface Area: 221.29 Å^2
• Rotatable Bonds: 14
• Lipinski's Rule of Five: false
• Acid pKa: 10.364198

PROPERTIES

Physical Property

• Solubility: DMSO

Safety Information

• Storage Condition: -20°C

Pharmacology Properties

• Target: Microtubule Formation

Product Information

• Salt Data: Free Base

DETAILS

Selleck Chemicals - S1150

Research Area

• Description: Cancer

Biological Activity

• Description: Paclitaxel (Taxol, Onxol, Nov-Onxol) is a microtubule polymer stabilizer with IC50 of 0.1 pM in human endothelial cells.
• Targets: Microtubule (human endothelial cells)
• IC50: 0.1 pM ^[1]
• In Vitro: Paclitaxel inhibits non-endothelial type human cells at 10^4 - to 10^5 -fold higher concentrations, with IC50 of 1 nM-10 nM. The selectivity of Paclitaxel inhibition of cell proliferation is also species specific, as mouse ECs are not sensitive to Paclitaxel at ultra low concentrations. Inhibition of human ECs by Paclitaxel at ultra low concentrations does not affect the cellular microtubule structure, and the treated cells do not show G2/M cell cycle arrest and apoptosis, suggesting a novel but as yet unidentified mechanism of action. In an in vitro angiogenesis assay, Paclitaxel at ultra low concentrations blocks human ECs from forming sprouts and tubes in the three-dimensional fibrin matrix. ^[1] In the presence of SMF, the efficient concentration of Paclitaxel on K562 cells is decreased from 50 to 10 ng/mL. The cell cycle arrest effect of Paclitaxel with or without SMF on K562 cells is correlated with DNA damage. ^[2] Paclitaxel alone causes a time-dependent inhibition of CDK1 in four cell lines including A549 cells, H358, H1395 cells and H1666 cells. ^[3]
• In Vivo: The inhibition rations of Paclitaxel alone on BC-V and BC-ER tumors are 49.78% and 51.23%, respectively. Treatment of six cycles of 20 mg/kg Paclitaxel significantly reduces the percentages of Ki-67-positive cells to 20.4% in BC-V tumors and 25.1% in BC-ER tumors, respectively. ^[5]
• Clinical Trials: Paclitaxel has entered in a Phase III clinical trial for the treatment of tubular breast cancer stage II, mucinous breast cancer stage II, breast cancer female NOS and invasive ductal breast cancer.

Combination Therapy

• Description: K562 cells treated with SMF plus Paclitaxel are arrested at the G2 phase, which is mainly induced by Paclitaxel. The potency of the combination of SMF and Paclitaxel is greater than that of SMF or Paclitaxel alone on K562 cells, and these effects are correlated with DNA damage induced by SMF and Paclitaxel. ^[2] The combination of Lobaplatin with antitubulin agents, especially with Paclitaxel, leads to significantly enhanced activity, which is superior to that of Cisplatin combined with antitubulin agents. ^[4] Paclitaxel in combination with Carboplatin, BIBW 2992, and Bevacizumab or BIBW2992 is currently under investigation in a Phase I clinical trial for the treatment of neoplasms.

Protocol

• Protocol: Cell Assay ^[1]
• Cell Lines: Cells including human neonatal dermal microvascular ECs (HMVECs), human umbilical vein ECs (HUVECs), human umbilical artery ECs (HUAVECs), normal human astrocytes (NHAs), normal human dermal fibroblasts (NHDFs), normal human epidermal keratinocytes (NHEKs), human mammary epithelial cells (HMEpCs), human prostate epithelial cells (PrEpCs) and human umbilical artery smooth muscle cells (UASMCs)
• Concentrations: 0.1-100 pM
• Incubation Time: 72 hours
• Methods: Cells including human neonatal dermal microvascular ECs (HMVECs), human umbilical vein ECs (HUVECs), human umbilical artery ECs (HUAVECs), normal human astrocytes (NHAs), normal human dermal fibroblasts (NHDFs), normal human epidermal keratinocytes (NHEKs), human mammary epithelial cells (HMEpCs), human prostate epithelial cells (PrEpCs) and human umbilical artery smooth muscle cells (UASMCs) are cultured. Cell proliferations are performed in 96-well plates using cells between passages 6 and 12. Cells are seeded at 3000–5000 cells/well and allowed to attach for 4 hours. Paclitaxel, diluted in culture medium, is added in quadruplicate wells and the cells ae incubated for 3 days before MTS reagents are added to quantitate the live cells in each well.
• Protocol: Animal Study ^[5]
• Animal Models: Female, 20-22 g homozygous nude athymic mice with BC-V and BC-ER tumors
• Formulation: Control
• Doses: 20 mg/kg
• Administration: Administered via i.v.

References

• References: [1] Wang J, et al. Anticancer Drugs. 2003, 14(1), 13-19.
• References: [2] Sun RG, et al. Gen Physiol Biophys. 2012, 31(1), 1-10.
• References: [3] Zhang XH, et al. Cancer Lett. 2012, 322(2), 213-222.
• References: [4] Xie CY, et al. Anticancer Drugs. 2012.
• References: [5] Chang J, et al. Breast Cancer Res Treat. 2012.

REFERENCES

• Wang J, et al. Anticancer Drugs. 2003, 14(1), 13-19.
• Sun RG, et al. Gen Physiol Biophys. 2012, 31(1), 1-10.
• Zhang XH, et al. Cancer Lett. 2012, 322(2), 213-222.
• Xie CY, et al. Anticancer Drugs. 2012.
• Chang J, et al. Breast Cancer Res Treat. 2012.