Paclitaxel docosahexaenoic acid
Identification
- Generic Name
- Paclitaxel docosahexaenoic acid
- DrugBank Accession Number
- DB05297
- Background
A combination of docosahexaenoic Acid (a natural fatty acid) and paclitaxel (an anticancer drug) being studied in the treatment of cancer. It is a type of mitotic inhibitor.
- Type
- Small Molecule
- Groups
- Investigational
- Structure
- Weight
- Average: 1164.3791
Monoisotopic: 1163.560620927 - Chemical Formula
- C69H81NO15
- Synonyms
- DHA Paclitaxel
- DHA-paclitaxel
- Paclitaxel 2'-(all-cis-4,7,10,13,16,19-docosahexaenoate)
- Paclitaxel docosahexaenoic acid ester
- PACLITAXEL-DHA
Pharmacology
- Indication
Investigated for use/treatment in breast cancer, colorectal cancer, gastric cancer, kidney cancer, lung cancer, pancreatic cancer, prostate cancer, and skin cancer.
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- 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.
Target Actions Organism UApoptosis regulator Bcl-2 Not Available Humans - 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
- Adverse Effects
- Improve decision support & research outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!Improve decision support & research outcomes with our structured adverse effects data.
- Toxicity
Not Available
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs
- Not Available
Interactions
- Drug Interactions
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.Not Available
- Food Interactions
- Not Available
Categories
- Drug Categories
- Chemical TaxonomyProvided by Classyfire
- 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
- Alcohol / Alpha-acyloxy ketone / Aromatic heteropolycyclic compound / Benzamide / Benzenoid / Benzoate ester / Benzoic acid or derivatives / Benzoyl / Beta amino acid or derivatives / Carbonyl group show 27 more
- Molecular Framework
- Aromatic heteropolycyclic compounds
- External Descriptors
- Not Available
- Affected organisms
- Not Available
Chemical Identifiers
- UNII
- OJE5810C4F
- CAS number
- 199796-52-6
- 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[11.3.1.0^{3,10}.0^{4,7}]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[C@H]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)[C@H](OC(=O)C)C(=C1C)C2(C)C)[C@@H](NC(=O)C1=CC=CC=C1)C1=CC=CC=C1
References
- General References
- 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. [Article]
- External Links
- PubChem Compound
- 6918473
- PubChem Substance
- 175426972
- ChemSpider
- 5293670
- ChEMBL
- CHEMBL4297441
- Wikipedia
- DHA-paclitaxel
Clinical Trials
- Clinical Trials
Phase Status Purpose Conditions Count 3 Completed Treatment Non-Small Cell Lung Cancer (NSCLC) 1 2 Unknown Status Treatment Colorectal Cancer 1 2 Unknown Status Treatment Pancreatic Cancer 1 2 Unknown Status Treatment Prostate Cancer 1 2 Unknown Status Treatment Renal Cancer 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
Property Value Source Water Solubility 7.67e-05 mg/mL ALOGPS logP 6.99 ALOGPS logP 10.96 Chemaxon logS -7.2 ALOGPS pKa (Strongest Acidic) 12.55 Chemaxon pKa (Strongest Basic) -1.2 Chemaxon Physiological Charge 0 Chemaxon Hydrogen Acceptor Count 10 Chemaxon Hydrogen Donor Count 3 Chemaxon Polar Surface Area 227.36 Å2 Chemaxon Rotatable Bond Count 30 Chemaxon Refractivity 326.19 m3·mol-1 Chemaxon Polarizability 124.76 Å3 Chemaxon Number of Rings 7 Chemaxon Bioavailability 0 Chemaxon Rule of Five No Chemaxon Ghose Filter No Chemaxon Veber's Rule No Chemaxon MDDR-like Rule Yes Chemaxon - Predicted ADMET Features
Property Value Probability Human Intestinal Absorption + 0.9667 Blood Brain Barrier - 0.8726 Caco-2 permeable - 0.7749 P-glycoprotein substrate Substrate 0.8351 P-glycoprotein inhibitor I Inhibitor 0.5682 P-glycoprotein inhibitor II Inhibitor 0.8041 Renal organic cation transporter Non-inhibitor 0.8906 CYP450 2C9 substrate Non-substrate 0.85 CYP450 2D6 substrate Non-substrate 0.8759 CYP450 3A4 substrate Substrate 0.7396 CYP450 1A2 substrate Non-inhibitor 0.83 CYP450 2C9 inhibitor Non-inhibitor 0.8511 CYP450 2D6 inhibitor Non-inhibitor 0.8988 CYP450 2C19 inhibitor Non-inhibitor 0.8049 CYP450 3A4 inhibitor Non-inhibitor 0.5382 CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.7223 Ames test Non AMES toxic 0.8105 Carcinogenicity Non-carcinogens 0.921 Biodegradation Not ready biodegradable 0.9666 Rat acute toxicity 2.4323 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.9909 hERG inhibition (predictor II) Non-inhibitor 0.7188
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
- Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 319.03806 predictedDeepCCS 1.0 (2019) [M+H]+ 320.7093 predictedDeepCCS 1.0 (2019) [M+Na]+ 326.86615 predictedDeepCCS 1.0 (2019)
Targets
- Kind
- Protein
- Organism
- Humans
- 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 at November 18, 2007 18:23 / Updated at July 18, 2023 22:56