Identification Name Patupilone Accession Number DB03010 (EXPT01349) Type Small Molecule Groups Experimental, Investigational Description
Epothilone B is a 16-membered macrolide that mimics the biological effects of taxol.
(−)-epothilone B Epo B Epothilone B External IDs EPO 906 / EPO 906A / EPO-906 / EPO-906A Product Ingredients Not Available Approved Prescription Products Not Available Approved Generic Prescription Products Not Available Approved Over the Counter Products Not Available Unapproved/Other Products Not Available International Brands Not Available Brand mixtures Not Available Categories UNII UEC0H0URSE CAS number 152044-54-7 Weight Average: 507.683 Monoisotopic: 507.265458739 Chemical Formula C 27H 41NO 6S InChI Key QXRSDHAAWVKZLJ-PVYNADRNSA-N InChI
SMILES Pharmacology Indication
Investigated for use/treatment in ovarian cancer, lung cancer, brain cancer, breast cancer, and gastric cancer.
Structured Indications Not Available Pharmacodynamics Not Available Mechanism of action
The principal mechanism of the epothilone class is inhibition of microtubule function. Microtubules are essential to cell division, and epothilones therefore stop cells from properly dividing. Epothilone B possess the same biological effects as taxol both in vitro and in cultured cells. This is because they share the same binding site, as well as binding affinity to the microtubule. Like taxol, epothilone B binds to the αβ-tubulin heterodimer subunit. Once bound, the rate of αβ-tubulin dissociation decreases, thus stabilizing the microtubules. Furthermore, epothilone B has also been shown to induce tubulin polymerization into microtubules without the presence of GTP. This is caused by formation of microtubule bundles throughout the cytoplasm. Finally, epothilone B also causes cell cycle arrest at the G2-M transition phase, thus leading to cytotoxicity and eventually cell apoptosis.
Target Kind Pharmacological action Actions Organism UniProt ID Tubulin alpha-3C/D chain Protein unknown Not Available Human Q13748 details Tubulin beta chain Protein unknown Not Available Human P07437 details Tubulin beta-1 chain Protein unknown Not Available Human Q9H4B7 details Tubulin beta-4B chain Protein unknown Not Available Human P68371 details Tubulin beta-4A chain Protein unknown Not Available Human P04350 details Tubulin alpha-4A chain Protein unknown Not Available Human P68366 details Tubulin beta-3 chain Protein unknown Not Available Human Q13509 details Tubulin alpha-1C chain Protein unknown Not Available Human Q9BQE3 details Tubulin alpha-8 chain Protein unknown Not Available Human Q9NY65 details Tubulin alpha-1B chain Protein unknown Not Available Human P68363 details Tubulin alpha-1A chain Protein unknown Not Available Human Q71U36 details Related Articles 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 Pathways Not Available Pharmacogenomic Effects/ADRs Not Available Interactions Drug Interactions
Drug Interaction Drug group Acetyldigitoxin Acetyldigitoxin may decrease the cardiotoxic activities of Epothilone B. Approved Bevacizumab Bevacizumab may increase the cardiotoxic activities of Epothilone B. Approved, Investigational Cabazitaxel The risk or severity of adverse effects can be increased when Cabazitaxel is combined with Epothilone B. Approved Cyclophosphamide Cyclophosphamide may increase the cardiotoxic activities of Epothilone B. Approved, Investigational Deslanoside Deslanoside may decrease the cardiotoxic activities of Epothilone B. Approved Digitoxin Digitoxin may decrease the cardiotoxic activities of Epothilone B. Approved Digoxin Digoxin may decrease the cardiotoxic activities of Epothilone B. Approved Docetaxel The risk or severity of adverse effects can be increased when Docetaxel is combined with Epothilone B. Approved, Investigational Oleandrin Anvirzel may decrease the cardiotoxic activities of Epothilone B. Experimental Ouabain Ouabain may decrease the cardiotoxic activities of Epothilone B. Approved Paclitaxel The risk or severity of adverse effects can be increased when Paclitaxel is combined with Epothilone B. Approved, Vet Approved Trastuzumab Trastuzumab may increase the cardiotoxic activities of Epothilone B. Approved, Investigational Food Interactions Not Available References Synthesis Reference
Richard Taylor, "Derivatives of epothilone B and D and synthesis thereof." U.S. Patent US20030176473, issued September 18, 2003.
US20030176473 General References Not Available External Links ATC Codes Not Available AHFS Codes Not Available PDB Entries FDA label Not Available MSDS Not Available Clinical Trials Clinical Trials
Phase Status Purpose Conditions Count 1 Completed Treatment Advanced Malignancies 1 1 Completed Treatment Advanced Malignancies / Tumors 2 1 Completed Treatment Advanced Malignancies / Tumors, Solid 1 1 Completed Treatment Advanced Solid Tumors 1 1 Completed Treatment Central Nervous System Neoplasms / Neoplasms, Head and Neck 1 1 Completed Treatment Malignant Neoplasm of Colon 1 1 Completed Treatment Refractory Malignancy 1 1 Completed Treatment Tumors 1 1 Completed Treatment Tumors, Solid 1 1 Terminated Treatment Advanced Malignancies 1 1 Withdrawn Treatment Tumors, Solid 1 1, 2 Completed Treatment Non-Small-Cell Lung Carcinoma (NSCLC) 1 1, 2 Completed Treatment Recurrent Glioblastoma Planned for Reoperation 1 2 Completed Treatment Abdominal wall neoplasm / Fallopian Tube Neoplasms / Neoplasms, Ovarian 1 2 Completed Treatment Brain Metastasis / Non-Small-Cell Lung Carcinoma (NSCLC) 1 2 Completed Treatment Cancer, Breast / Metastatic Cancers 1 2 Completed Treatment Carcinoids / Neuroendocrine Tumors 1 2 Completed Treatment Colonic Neoplasms / Neoplasms, Colorectal 1 2 Completed Treatment Hepatocellular,Carcinoma 1 2 Completed Treatment Hormone Refractory Prostate Cancer 1 2 Completed Treatment Melanoma 1 2 Completed Treatment Metastatic Hormone Refractory Prostate Cancer 1 2 Completed Treatment Neoplasms, Breast 1 2 Completed Treatment Neoplasms, Kidney 1 2 Completed Treatment Prostatic Neoplasms 1 3 Completed Treatment Abdominal wall neoplasm / Cancer, Ovarian / Fallopian Tube 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 Predicted ADMET features
Property Value Probability Human Intestinal Absorption + 0.8471 Blood Brain Barrier + 0.6791 Caco-2 permeable - 0.5935 P-glycoprotein substrate Substrate 0.7384 P-glycoprotein inhibitor I Non-inhibitor 0.8232 P-glycoprotein inhibitor II Non-inhibitor 0.9779 Renal organic cation transporter Non-inhibitor 0.9193 CYP450 2C9 substrate Non-substrate 0.84 CYP450 2D6 substrate Non-substrate 0.8309 CYP450 3A4 substrate Substrate 0.622 CYP450 1A2 substrate Inhibitor 0.5065 CYP450 2C9 inhibitor Non-inhibitor 0.7468 CYP450 2D6 inhibitor Non-inhibitor 0.9114 CYP450 2C19 inhibitor Non-inhibitor 0.6114 CYP450 3A4 inhibitor Non-inhibitor 0.7163 CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.8841 Ames test Non AMES toxic 0.5816 Carcinogenicity Non-carcinogens 0.933 Biodegradation Ready biodegradable 0.5 Rat acute toxicity 2.7983 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.9924 hERG inhibition (predictor II) Non-inhibitor 0.935
ADMET data is predicted using
, a free tool for evaluating chemical ADMET properties. (
Spectra Mass Spec (NIST) Not Available Spectra Taxonomy Description This compound belongs to the class of chemical entities known as epothilones and analogues. These are macrolides consisting of a 16-member lactone ring conjugated at the carbon 16 with a 1-(2-methyl-1,3-thiazol-4-yl)prop-1-en-2-yl group. Some epothilone analogues containing a lactam ring instead of the lactone ring. Kingdom Chemical entities Super Class Organic compounds Class Phenylpropanoids and polyketides Sub Class Macrolides and analogues Direct Parent Epothilones and analogues Alternative Parents 2,4-disubstituted thiazoles / Heteroaromatic compounds / Secondary alcohols / Lactones / Cyclic ketones / Carboxylic acid esters / Oxacyclic compounds / Monocarboxylic acids and derivatives / Epoxides / Dialkyl ethers / Azacyclic compounds / Organopnictogen compounds / Organonitrogen compounds / Organic oxides / Hydrocarbon derivatives show 5 more Substituents Epothilone / 2,4-disubstituted 1,3-thiazole / Azole / Heteroaromatic compound / Thiazole / Carboxylic acid ester / Ketone / Lactone / Secondary alcohol / Cyclic ketone / Carboxylic acid derivative / Dialkyl ether / Oxirane / Ether / Oxacycle / Monocarboxylic acid or derivatives / Azacycle / Organoheterocyclic compound / Organic oxide / Organic oxygen compound / Hydrocarbon derivative / Carbonyl group / Organic nitrogen compound / Organonitrogen compound / Organooxygen compound / Organopnictogen compound / Alcohol / Aromatic heteropolycyclic compound show 18 more Molecular Framework Aromatic heteropolycyclic compounds External Descriptors 1,3-thiazole, oxabicycloalkane ( CHEBI:42432 ) / Macrolides and lactone polyketides ( C12154 ) / Macrolides and lactone polyketides ( LMPK04000041 )