生物活性

• 描述Microtubules are the main constituent of mitotic apparatus in all eukaryotic cells, thus make it become an important pharmacological target for the treatment of tumor^[1]. Paclitaxel can stabilize the microtubule formation through interacting with β-tubulin^[2] and then promoting the polymerization and assembly of it^[3]. Paclitaxel show the inhibitory effect on HMVEC proliferation with IC50 of 0.1 pM, much lower than the IC50 of 5-FU, camptothecin, cisplatin and doxorubicin^[4]. Paclitaxel induces G2/M arrest of cell cycle, thus it also used in synchronization in cell cycle^[5]. Paclitaxel was approved by FDA in treatment of ovarian cancer, breast cancer, non-small-cell lung cancer^[6], etc..
• 作用机制Paclitaxel can stabilize the microtubule formation through interacting with β-tubulin^[2] and then promoting the polymerization and assembly of it^[3].
• 细胞研究
• Cell Data

  Cell Lines	Concentration	Assay Type	Time	Activity Description	Data Sources
  697	-	Growth Inhibition Assay	-	IC50=0.0015 μM	SANGER
  8-MG-BA	-	Growth Inhibition Assay	-	IC50=0.00796 μM	SANGER
  A101D	-	Growth Inhibition Assay	-	IC50=0.0096 μM	SANGER

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• 动物研究
  剂量	Mice: min = 2 mg/kg[7] (i.v.), max = 75 mg/kg[8] (i.p.)
  给药途径	i.v., i.p.
  动物药代数据	Animal Rats[9] Dose 30 mg/kg Administration p.o. Cmax 67.0 ± 14.3 ng/ml T1/2 4.1 ± 1.2 h AUC0→∞ 321.2 ± 79.7 h·ng/ml CL/F 143.3 ± 51.3 L/h/kg Tmax 1.6 ± 0.2 h AUC0→24h 299.8 ± 77.8 h·ng/ml V/F 321.5 ± 102.7 L/kg

• 临床研究

• NCT号	适应症或疾病	临床期	招募状态	预计完成时间	地点
  NCT02244502	Ovarian Carcinoma	Phase 1 Phase 2	Unknown	December 2016	Belgium ... more >> Leuven, Belgium Germany Charité - Universitätsmedizin Berlin Berlin, Germany Spain Hospitale Universitario 12 de Octubre Madrid, Spain Switzerland Ospedale San Giovanni Bellinzona, Switzerland Kantonsspital Graubünden Chur, Switzerland Collapse <<
  NCT03636308	Pancreatic Cancer	Phase 2	Recruiting	August 1, 2021	China, Beijing ... more >> Peking University Cancer Hospital and Institute Recruiting Beijing, Beijing, China, 100142 Contact: Jun Zhou, MD Collapse <<
  NCT02501902	Metastatic Pancreatic Ductal A... more >>denocarcinoma Collapse <<	Phase 1	Recruiting	December 27, 2018	United States, Arizona ... more >> Scottsdale Healthcare Hospitals DBA HonorHealth Active, not recruiting Scottsdale, Arizona, United States, 85258 Virginia G. Piper Cancer Pharmacy Active, not recruiting Scottsdale, Arizona, United States, 85258 United States, California UCSD Medical Center - Encinitas Active, not recruiting Encinitas, California, United States, 92024 UC San Diego Medical Center - La Jolla (Thornton Hospital) Active, not recruiting La Jolla, California, United States, 92037-0845 UC San Diego Moores Cancer Center - Investigational Drug Services Active, not recruiting La Jolla, California, United States, 92037-0845 UC San Diego Moores Cancer Center Active, not recruiting La Jolla, California, United States, 92093 UC San Diego Medical Center - Hillcrest Active, not recruiting San Diego, California, United States, 92103 UCSD Medical Center - Vista Active, not recruiting Vista, California, United States, 92081 United States, Colorado Drug Shipment Address: Anschutz Cancer Pavilion Active, not recruiting Aurora, Colorado, United States, 80045 University of Colorado Cancer Center Active, not recruiting Aurora, Colorado, United States, 80045 University of Colorado Denver, CTO (CTRC) Active, not recruiting Aurora, Colorado, United States, 80045 University of Colorado Hospital - Anschutz Inpatient Pavilion (AIP) Active, not recruiting Aurora, Colorado, United States, 80045 University of Colorado Hospital - Anschutz Outpatient Pavilion (AOP) Active, not recruiting Aurora, Colorado, United States, 80045 United States, Maryland The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Active, not recruiting Baltimore, Maryland, United States, 21231-1000 United States, Massachusetts Beth Israel Deaconess Medical Center Active, not recruiting Boston, Massachusetts, United States, 02215 United States, Missouri Siteman Cancer Center - West County Active, not recruiting Creve Coeur, Missouri, United States, 63141 Barnes-Jewish Hospital Active, not recruiting Saint Louis, Missouri, United States, 63110 Washington University Infusion Center Pharmacy Active, not recruiting Saint Louis, Missouri, United States, 63110 Washington University School of Medicine Active, not recruiting Saint Louis, Missouri, United States, 63110 Siteman Cancer Center - South County Active, not recruiting Saint Louis, Missouri, United States, 63129 Siteman Cancer Center Active, not recruiting Saint Peters, Missouri, United States, 63376 United States, Utah University of Utah, Huntsman Cancer Hospital Active, not recruiting Salt Lake City, Utah, United States, 84112 University of Utah, Huntsman Cancer Institute Active, not recruiting Salt Lake City, Utah, United States, 84112 Spain Hospital Universitario de Fuenlabrada. Unidad de Farmacia (Only Drug Shipment) Recruiting Fuenlabrada, Madrid, Spain, 28942 Hospital Universitario Fuenlabrada Recruiting Fuenlabrada, Madrid, Spain, 28942 Hospital Universitari Vall D'Hebron Active, not recruiting Barcelona, Spain, 08035 Hospital Universitario 12 de Octubre Servicio de Farmacia Recruiting Madrid, Spain, 28041 Hospital Universitario 12 de Octubre Recruiting Madrid, Spain, 28041 Collapse <<

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• 参考文献

• [1] Fong KW, Leung JW, et al. MTR120/KIAA1383, a novel microtubule-associated protein, promotes microtubule stability and ensures cytokinesis. J Cell Sci. 2013 Feb 1;126(Pt 3):825-37.

  [2] Snyder JP, Nettles JH, et al. The binding conformation of Taxol in beta-tubulin: a model based on electron crystallographic density. Proc Natl Acad Sci U S A. 2001 Apr 24;98(9):5312-6. Epub 2001 Apr 17.

  [3] Schiff PB, Fant J, et al. Promotion of microtubule assembly in vitro by taxol. Nature. 1979 Feb 22;277(5698):665-7.

  [4] Wang J, Lou P, et al. Paclitaxel at ultra low concentrations inhibits angiogenesis without affecting cellular microtubule assembly. Anticancer Drugs. 2003 Jan;14(1):13-9.

  [5] Trielli MO, Andreassen PR, et al. Differential Taxol-dependent arrest of transformed and nontransformed cells in the G1 phase of the cell cycle, and specific-related mortality of transformed cells. J Cell Biol. 1996 Nov;135(3):689-700.

  [6] Shi X, Sun X, et al. Regulation of paclitaxel activity by microtubule-associated proteins in cancer chemotherapy. Cancer Chemother Pharmacol. 2017 Nov;80(5):909-917.

  [7] Sparreboom A, van Tellingen O, et al. Nonlinear pharmacokinetics of paclitaxel in mice results from the pharmaceutical vehicle Cremophor EL. Cancer Res. 1996 May 1;56(9):2112-5.

  [8] Cividalli A, Cruciani G, et al. Greater antitumor efficacy of paclitaxel administered before epirubicin in a mouse mammary carcinoma. J Cancer Res Clin Oncol. 1998;124(5):236-44.

  [9] Jin J, Cai D, et al. Comparative pharmacokinetics of paclitaxel after oral administration of Taxus yunnanensis extract and pure paclitaxel to rats. Fitoterapia. 2013 Oct;90:1-9.

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