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Identification
NameDHA-paclitaxel
Accession NumberDB05297
TypeSmall Molecule
GroupsInvestigational
DescriptionA 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
SynonymsNot Available
External Identifiers Not Available
Approved Prescription ProductsNot Available
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International BrandsNot Available
Brand mixturesNot Available
SaltsNot Available
CategoriesNot Available
UNIIOJE5810C4F
CAS numberNot Available
WeightAverage: 1164.3791
Monoisotopic: 1163.560620927
Chemical FormulaC69H81NO15
InChI KeyInChIKey=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[C@@H](C(=O)O[[email protected]]1C[C@@]2(O)[C@@H](OC(=O)C3=CC=CC=C3)[C@@]3([H])[C@@](C)([C@@H](O)C[C@@]4([H])OC[C@@]34OC(=O)C)C(=O)[[email protected]](OC(=O)C)C(=C1C)C2(C)C)[C@@H](NC(=O)C1=CC=CC=C1)C1=CC=CC=C1
Taxonomy
DescriptionThis 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
KingdomOrganic compounds
Super ClassLipids and lipid-like molecules
ClassPrenol lipids
Sub ClassDiterpenoids
Direct ParentTaxanes and derivatives
Alternative Parents
Substituents
  • Taxane diterpenoid
  • N-benzylbenzamide
  • Beta amino acid or derivatives
  • Phenylpropylamine
  • Benzoate ester
  • Tricarboxylic acid or derivatives
  • Benzylether
  • Benzoic acid or derivatives
  • Benzamide
  • Benzoyl
  • Alpha-acyloxy ketone
  • Fatty acid ester
  • Fatty acyl
  • Benzenoid
  • Monosaccharide
  • Monocyclic benzene moiety
  • Acetate salt
  • Tertiary alcohol
  • Cyclic alcohol
  • Secondary carboxylic acid amide
  • Secondary alcohol
  • Oxetane
  • Ketone
  • Carboxylic acid ester
  • Carboxamide group
  • Oxacycle
  • Organoheterocyclic compound
  • Ether
  • Dialkyl ether
  • Carboxylic acid derivative
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organonitrogen compound
  • Carbonyl group
  • Alcohol
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External DescriptorsNot Available
Pharmacology
IndicationInvestigated for use/treatment in breast cancer, colorectal cancer, gastric cancer, kidney cancer, lung cancer, pancreatic cancer, prostate cancer, and skin cancer.
PharmacodynamicsNot Available
Mechanism of actionA 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.
Related Articles
AbsorptionNot Available
Volume of distributionNot Available
Protein bindingNot Available
MetabolismNot Available
Route of eliminationNot Available
Half lifeNot Available
ClearanceNot Available
ToxicityNot Available
Affected organismsNot Available
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
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 )
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage formsNot Available
PricesNot Available
PatentsNot Available
Properties
StateSolid
Experimental PropertiesNot 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 FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
SpectraNot Available
References
Synthesis ReferenceNot Available
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
ATC CodesNot Available
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
Interactions
Drug InteractionsNot Available
Food InteractionsNot 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. Appears to function in a feedback loop system with caspases. Inhibits caspase activity either by preventing the release of cytochrome c from the mitochondria and/or by binding to the apoptosis-activating f...
Gene Name:
BCL2
Uniprot ID:
P10415
Molecular Weight:
26265.66 Da
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Drug created on November 18, 2007 11:23 / Updated on August 17, 2016 12:24