Details of the Drug

General Information of Drug (ID: DMLB81S)

Drug Name
Paclitaxel
Synonyms
5beta,20-Epoxy-1,2-alpha,4,7beta,10beta,13alpha-hexahydroxytax-11-en-9-one 4,10-diacetate 2-benzoate 13-ester with (2R,3S)-N-b; 7-epi-Paclitaxel; ABI-007; Abraxane; Capxol; Ebetaxel; EmPAC; Genaxol; Genetaxyl; Genexol; Intaxel; LipoPac; OncoGel; Onxol; Paclitaxel (Taxol); Paxceed; Paxene; Plaxicel; TAXOL; TaxAlbin; Taxol A; Xorane; Yewtaxan; Zisu; nab-paclitaxel; paclitaxel
Indication
Disease Entry ICD 11 Status REF
Breast carcinoma N.A. Approved [1]
Cutaneous melanoma 2C30 Approved [1]
Cutaneous squamous cell carcinoma 2C30 Approved [1]
Epithelial ovarian cancer 2B5D Approved [1]
Extragonadal germ cell tumor N.A. Approved [1]
Fallopian tube neoplasm N.A. Approved [1]
Gastroesophageal junction adenocarcinoma 2B71 Approved [1]
Inflammatory breast cancer 2C62 Approved [1]
Kaposi sarcoma 2B57 Approved [1]
Lung adenocarcinoma N.A. Approved [1]
Lung cancer 2C25.0 Approved [1]
Non-small-cell lung cancer 2C25.Y Approved [1]
Ocular hypertension 9C61.01 Approved [1]
Ovarian neoplasm N.A. Approved [1]
Ovarian serous cystadenocarcinoma N.A. Approved [1]
Pain MG30-MG3Z Approved [1]
Pancreatic ductal carcinoma 2C10.0 Approved [1]
Primary peritoneal carcinoma N.A. Approved [1]
Testicular germ cell tumor N.A. Approved [1]
Urethral cancer 2C93 Approved [1]
Lung large cell carcinoma N.A. Investigative [1]
⏷ Show the Full List of Indication(s)
Therapeutic Class
Anticancer Agents
Drug Type
Small molecular drug
Structure
3D MOL 2D MOL
#Ro5 Violations (Lipinski): 3 Molecular Weight (mw) 853.918
Logarithm of the Partition Coefficient (xlogp) 2.5
Rotatable Bond Count (rotbonds) 14
Hydrogen Bond Donor Count (hbonddonor) 4
Hydrogen Bond Acceptor Count (hbondacc) 14
ADMET Property
BDDCS Class
Biopharmaceutics Drug Disposition Classification System (BDDCS) Class 2: low solubility and high permeability [2]
Clearance
The drug present in the plasma can be removed from the body at the rate of 6.4 mL/min/kg [3]
Elimination
5% of drug is excreted from urine in the unchanged form [2]
Half-life
The concentration or amount of drug in body reduced by one-half in 24 hours [3]
Metabolism
The drug is metabolized via the hepatic []
MRTD
The Maximum Recommended Therapeutic Dose (MRTD) of drug that ensured maximising efficacy and moderate side effect is 5.5391 micromolar/kg/day [4]
Unbound Fraction
The unbound fraction of drug in plasma is 0.12% [3]
Vd
Fluid volume that would be required to contain the amount of drug present in the body at the same concentration as in the plasma 3 L/kg [3]
Adverse Drug Reaction (ADR)
ADR Term Variation Related DOT DOT ID REF
Apoptosis Not Available SOD2 OT08HOR5 [5]
Apoptosis Not Available MOS OTNMQPFJ [5]
Apoptosis Not Available NFKB1 OTNRRD8I [5]
Apoptosis Not Available DAD1 OTUUNQBT [5]
Cytogenetic abnormality Not Available PLK2 OTKMJXJ8 [5]
Mitochondrial toxicity Not Available PARP1 OTIESHK4 [5]
Vascular disorders Not Available ALPL OTG7J4BP [5]
Vascular disorders Not Available VWF OTNMMA2P [5]
Vascular disorders Not Available LPL OTTW0267 [5]
⏷ Show the Full List of 9 ADR Information of This Drug
Chemical Identifiers
Formula
C47H51NO14
IUPAC Name
[(1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-diacetyloxy-15-[(2R,3S)-3-benzamido-2-hydroxy-3-phenylpropanoyl]oxy-1,9-dihydroxy-10,14,17,17-tetramethyl-11-oxo-6-oxatetracyclo[11.3.1.03,10.04,7]heptadec-13-en-2-yl] benzoate
Canonical SMILES
CC1=C2C(C(=O)C3(C(CC4C(C3C(C(C2(C)C)(CC1OC(=O)C(C(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
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-MZXODVADSA-N
Cross-matching ID
PubChem CID
36314
ChEBI ID
ChEBI:45863
CAS Number
33069-62-4
DrugBank ID
DB01229
VARIDT ID
DR00342
Combinatorial Drugs (CBD) Click to Jump to the Detailed CBD Information of This Drug
Repurposed Drugs (RPD) Click to Jump to the Detailed RPD Information of This Drug

Molecular Interaction Atlas of This Drug


Drug Transporter (DTP)
DTP Name DTP ID UniProt ID MOA REF
Multidrug resistance protein 3 (ABCB4) DTZRMK5 MDR3_HUMAN Substrate [6]
TAP-like protein (ABCB9) DT68UV2 ABCB9_HUMAN Substrate [7]
Multidrug resistance-associated protein 7 (ABCC10) DTPS120 MRP7_HUMAN Substrate [8]
Organic anion transporter 2 (SLC22A7) DT0OC1Q S22A7_HUMAN Substrate [9]
Multidrug resistance-associated protein 3 (ABCC3) DTQ3ZHF MRP3_HUMAN Substrate [10]
Multidrug resistance-associated protein 2 (ABCC2) DTFI42L MRP2_HUMAN Substrate [11]
Multidrug resistance-associated protein 1 (ABCC1) DTSYQGK MRP1_HUMAN Substrate [12]
Breast cancer resistance protein (ABCG2) DTI7UX6 ABCG2_HUMAN Substrate [13]
Organic anion transporting polypeptide 1B1 (SLCO1B1) DT3D8F0 SO1B1_HUMAN Substrate [14]
Organic anion transporting polypeptide 1B3 (SLCO1B3) DT9C1TS SO1B3_HUMAN Substrate [15]
P-glycoprotein 1 (ABCB1) DTUGYRD MDR1_HUMAN Substrate [16]

Drug Off-Target (DOT)
DOT Name DOT ID UniProt ID Interaction REF
1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase epsilon-1 (PLCE1) OTJISZOX PLCE1_HUMAN Drug Response [17]
14-3-3 protein theta OTWG7F3H 1433T_HUMAN Gene/Protein Processing [18]
3-phosphoinositide-dependent protein kinase 1 (PDPK1) OTT09ZVP PDPK1_HUMAN Drug Response [19]
4-trimethylaminobutyraldehyde dehydrogenase (ALDH9A1) OTNWHUJ1 AL9A1_HUMAN Gene/Protein Processing [20]
Abnormal spindle-like microcephaly-associated protein (ASPM) OTKXQMNA ASPM_HUMAN Gene/Protein Processing [21]
Acidic leucine-rich nuclear phosphoprotein 32 family member A (ANP32A) OTRHPFO2 AN32A_HUMAN Drug Response [22]
Actin, aortic smooth muscle (ACTA2) OTEDLG8E ACTA_HUMAN Gene/Protein Processing [23]
Activated RNA polymerase II transcriptional coactivator p15 (SUB1) OTK71JYU TCP4_HUMAN Gene/Protein Processing [20]
Acyl-coenzyme A thioesterase 8 (ACOT8) OTHY684G ACOT8_HUMAN Gene/Protein Processing [24]
Adenylate cyclase type 6 (ADCY6) OTFOY4WW ADCY6_HUMAN Gene/Protein Processing [25]
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This Drug

References

1 Paclitaxel FDA Label
2 BDDCS applied to over 900 drugs
3 Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
4 Estimating the safe starting dose in phase I clinical trials and no observed effect level based on QSAR modeling of the human maximum recommended daily dose
5 ADReCS-Target: target profiles for aiding drug safety research and application. Nucleic Acids Res. 2018 Jan 4;46(D1):D911-D917. doi: 10.1093/nar/gkx899.
6 MDR3 P-glycoprotein, a phosphatidylcholine translocase, transports several cytotoxic drugs and directly interacts with drugs as judged by interference with nucleotide trapping. J Biol Chem. 2000 Aug 4;275(31):23530-9.
7 Overexpression of microRNA-24 increases the sensitivity to paclitaxel in drug-resistant breast carcinoma cell lines via targeting ABCB9. Oncol Lett. 2016 Nov;12(5):3905-3911.
8 Modulation of the ATPase and transport activities of broad-acting multidrug resistance factor ABCC10 (MRP7). Cancer Res. 2012 Dec 15;72(24):6457-67.
9 Transport mechanism and substrate specificity of human organic anion transporter 2 (hOat2 [SLC22A7]). J Pharm Pharmacol. 2005 May;57(5):573-8.
10 Functional genomics identifies ABCC3 as a mediator of taxane resistance in HER2-amplified breast cancer. Cancer Res. 2008 Jul 1;68(13):5380-9.
11 Multidrug resistance protein 2 is an important determinant of paclitaxel pharmacokinetics. Clin Cancer Res. 2006 Oct 15;12(20 Pt 1):6125-32.
12 Human intestinal transporter database: QSAR modeling and virtual profiling of drug uptake, efflux and interactions. Pharm Res. 2013 Apr;30(4):996-1007.
13 Ixabepilone, a novel microtubule-targeting agent for breast cancer, is a substrate for P-glycoprotein (P-gp/MDR1/ABCB1) but not breast cancer resistance protein (BCRP/ABCG2). J Pharmacol Exp Ther. 2011 May;337(2):423-32.
14 Interaction of human organic anion transporter polypeptides 1B1 and 1B3 with antineoplastic compounds. Eur J Med Chem. 2015 Mar 6;92:723-31.
15 Identification of OATP1B3 as a high-affinity hepatocellular transporter of paclitaxel. Cancer Biol Ther. 2005 Aug;4(8):815-8.
16 Kinetics of P-glycoprotein-mediated efflux of paclitaxel. J Pharmacol Exp Ther. 2001 Sep;298(3):1236-42.
17 Gene expression analysis using human cancer xenografts to identify novel predictive marker genes for the efficacy of 5-fluorouracil-based drugs. Cancer Sci. 2006 Jun;97(6):510-22. doi: 10.1111/j.1349-7006.2006.00204.x.
18 Susceptibility to drug-induced apoptosis correlates with differential modulation of Bad, Bcl-2 and Bcl-xL protein levels. Cell Death Differ. 2000 Jun;7(6):574-86. doi: 10.1038/sj.cdd.4400688.
19 Differential roles of phosphoinositide-dependent protein kinase-1 and akt1 expression and phosphorylation in breast cancer cell resistance to Paclitaxel, Doxorubicin, and gemcitabine. Mol Pharmacol. 2006 Sep;70(3):1045-52. doi: 10.1124/mol.106.023333. Epub 2006 Jun 16.
20 Proteomic analysis of anti-cancer effects by paclitaxel treatment in cervical cancer cells. Gynecol Oncol. 2005 Jul;98(1):45-53. doi: 10.1016/j.ygyno.2005.04.010.
21 Characterization of DNA reactive and non-DNA reactive anticancer drugs by gene expression profiling. Mutat Res. 2007 Jun 1;619(1-2):16-29. doi: 10.1016/j.mrfmmm.2006.12.007. Epub 2007 Feb 8.
22 Gene expression profiling of 30 cancer cell lines predicts resistance towards 11 anticancer drugs at clinically achieved concentrations. Int J Cancer. 2006 Apr 1;118(7):1699-712. doi: 10.1002/ijc.21570.
23 Association of cell cycle arrest with anticancer drug-induced epithelial-mesenchymal transition in alveolar epithelial cells. Toxicology. 2019 Aug 1;424:152231. doi: 10.1016/j.tox.2019.06.002. Epub 2019 Jun 4.
24 Orlistat Displays Antitumor Activity and Enhances the Efficacy of Paclitaxel in Human Hepatoma Hep3B Cells. Chem Res Toxicol. 2019 Feb 18;32(2):255-264. doi: 10.1021/acs.chemrestox.8b00269. Epub 2019 Jan 22.
25 Effects of paclitaxel on proliferation and apoptosis in human acute myeloid leukemia HL-60 cells. Acta Pharmacol Sin. 2004 Mar;25(3):378-84.