Paclitaxel docosahexaenoic acid

Identification

Name
Paclitaxel docosahexaenoic acid
Accession Number
DB05297
Type
Small Molecule
Groups
Investigational
Description

A combination of DHA (a natural fatty acid) and paclitaxel (an anticancer drug) being studied in the treatment of cancer. It is a type of mitotic inhibitor.

Structure
Thumb
Synonyms
  • DHA Paclitaxel
  • DHA-paclitaxel
  • Paclitaxel 2'-(all-cis-4,7,10,13,16,19-docosahexaenoate)
  • Paclitaxel docosahexaenoic acid ester
Categories
UNII
OJE5810C4F
CAS number
199796-52-6
Weight
Average: 1164.3791
Monoisotopic: 1163.560620927
Chemical Formula
C69H81NO15
InChI Key
LRCZQSDQZJBHAF-PUBGEWHCSA-N
InChI
InChI=1S/C69H81NO15/c1-8-9-10-11-12-13-14-15-16-17-18-19-20-21-22-23-24-25-35-42-55(74)83-59(57(49-36-29-26-30-37-49)70-63(76)50-38-31-27-32-39-50)65(78)82-52-44-69(79)62(84-64(77)51-40-33-28-34-41-51)60-67(7,53(73)43-54-68(60,45-80-54)85-48(4)72)61(75)58(81-47(3)71)56(46(52)2)66(69,5)6/h9-10,12-13,15-16,18-19,21-22,24-34,36-41,52-54,57-60,62,73,79H,8,11,14,17,20,23,35,42-45H2,1-7H3,(H,70,76)/b10-9-,13-12-,16-15-,19-18-,22-21-,25-24-/t52-,53-,54+,57-,58+,59+,60-,62-,67+,68-,69+/m0/s1
IUPAC Name
(1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-bis(acetyloxy)-15-{[(2R,3S)-2-[(4Z,7Z,10Z,13Z,16Z,19Z)-docosa-4,7,10,13,16,19-hexaenoyloxy]-3-phenyl-3-(phenylformamido)propanoyl]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
SMILES
CC\C=C/C\C=C/C\C=C/C\C=C/C\C=C/C\C=C/CCC(=O)O[[email protected]@H](C(=O)O[[email protected]]1C[[email protected]@]2(O)[[email protected]@H](OC(=O)C3=CC=CC=C3)[[email protected]@]3([H])[[email protected]@](C)([[email protected]@H](O)C[[email protected]@]4([H])OC[[email protected]@]34OC(=O)C)C(=O)[[email protected]](OC(=O)C)C(=C1C)C2(C)C)[[email protected]@H](NC(=O)C1=CC=CC=C1)C1=CC=CC=C1

Pharmacology

Indication

Investigated for use/treatment in breast cancer, colorectal cancer, gastric cancer, kidney cancer, lung cancer, pancreatic cancer, prostate cancer, and skin cancer.

Structured Indications
Not Available
Pharmacodynamics
Not Available
Mechanism of action

A prodrug comprised of the naturally occurring omega-3 fatty acid docosahexaenoic acid (DHA) covalently conjugated to the anti-microtubule agent paclitaxel. Because tumor cells take up DHA, DHA-paclitaxel is delivered directly to tumor tissue, where the paclitaxel moiety binds to tubulin and inhibits the disassembly of microtubules, thereby resulting in the inhibition of cell division. Paclitaxel also induces apoptosis by binding to and blocking the function of the apoptosis inhibitor protein Bcl-2 (B-cell Leukemia 2). DHA-paclitaxel exhibits improved pharmacokinetic and toxicity profiles when compared to conventional paclitaxel and has demonstrated antineoplastic activity in animal models of cancer.

TargetActionsOrganism
UApoptosis regulator Bcl-2Not AvailableHuman
Absorption
Not Available
Volume of distribution
Not Available
Protein binding
Not Available
Metabolism
Not Available
Route of elimination
Not Available
Half life
Not Available
Clearance
Not Available
Toxicity
Not Available
Affected organisms
Not Available
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
Not Available
Food Interactions
Not Available

References

General References
  1. Bradley MO, Swindell CS, Anthony FH, Witman PA, Devanesan P, Webb NL, Baker SD, Wolff AC, Donehower RC: Tumor targeting by conjugation of DHA to paclitaxel. J Control Release. 2001 Jul 6;74(1-3):233-6. [PubMed:11489499]
External Links
PubChem Compound
6918473
PubChem Substance
175426972
ChemSpider
5293670
Wikipedia
DHA-paclitaxel

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
2Unknown StatusTreatmentColorectal Cancers1
2Unknown StatusTreatmentMalignant Neoplasm of Pancreas1
2Unknown StatusTreatmentProstate Cancer1
2Unknown StatusTreatmentRenal Cancers1
3CompletedTreatmentLung Cancer Non-Small Cell Cancer (NSCLC)1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility7.67e-05 mg/mLALOGPS
logP6.99ALOGPS
logP10.96ChemAxon
logS-7.2ALOGPS
pKa (Strongest Acidic)10.37ChemAxon
pKa (Strongest Basic)-1ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count10ChemAxon
Hydrogen Donor Count3ChemAxon
Polar Surface Area227.36 Å2ChemAxon
Rotatable Bond Count30ChemAxon
Refractivity326.19 m3·mol-1ChemAxon
Polarizability124.21 Å3ChemAxon
Number of Rings7ChemAxon
Bioavailability0ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9667
Blood Brain Barrier-0.8726
Caco-2 permeable-0.7749
P-glycoprotein substrateSubstrate0.8351
P-glycoprotein inhibitor IInhibitor0.5682
P-glycoprotein inhibitor IIInhibitor0.8041
Renal organic cation transporterNon-inhibitor0.8906
CYP450 2C9 substrateNon-substrate0.85
CYP450 2D6 substrateNon-substrate0.8759
CYP450 3A4 substrateSubstrate0.7396
CYP450 1A2 substrateNon-inhibitor0.83
CYP450 2C9 inhibitorNon-inhibitor0.8511
CYP450 2D6 inhibitorNon-inhibitor0.8988
CYP450 2C19 inhibitorNon-inhibitor0.8049
CYP450 3A4 inhibitorNon-inhibitor0.5382
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.7223
Ames testNon AMES toxic0.8105
CarcinogenicityNon-carcinogens0.921
BiodegradationNot ready biodegradable0.9666
Rat acute toxicity2.4323 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9909
hERG inhibition (predictor II)Non-inhibitor0.7188
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as taxanes and derivatives. These are diterpenoids with a structure based either on the taxane skeleton, or a derivative thereof. In term of phytochemistry, several derivatives of the taxane skeleton exist: 2(3->20)-abeotaxane, 3,11-cyclotaxane, 11(15->1),11(10->9)-abeotaxane, 3,8-seco-taxane, and 11(15->1)-abeotaxane, among others. More complex skeletons have been found recently, which include the taxane-derived [3.3.3] propellane ring system.
Kingdom
Organic compounds
Super Class
Lipids and lipid-like molecules
Class
Prenol lipids
Sub Class
Diterpenoids
Direct Parent
Taxanes and derivatives
Alternative Parents
Pentacarboxylic acids and derivatives / N-benzylbenzamides / Beta amino acids and derivatives / Benzoic acid esters / Benzoyl derivatives / Alpha-acyloxy ketones / Fatty acid esters / Monosaccharides / Tertiary alcohols / Secondary carboxylic acid amides
show 11 more
Substituents
Taxane diterpenoid / N-benzylbenzamide / Pentacarboxylic acid or derivatives / Beta amino acid or derivatives / Benzoate ester / Benzamide / Benzoic acid or derivatives / Benzoyl / Alpha-acyloxy ketone / Fatty acid ester
show 27 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
Not Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Ubiquitin protein ligase binding
Specific Function
Suppresses apoptosis in a variety of cell systems including factor-dependent lymphohematopoietic and neural cells. Regulates cell death by controlling the mitochondrial membrane permeability. Appea...
Gene Name
BCL2
Uniprot ID
P10415
Uniprot Name
Apoptosis regulator Bcl-2
Molecular Weight
26265.66 Da

Drug created on November 18, 2007 11:23 / Updated on December 01, 2017 15:35