Sagopilone

This drug entry is a stub and has not been fully annotated. It is scheduled to be annotated soon.

Identification

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Name
Sagopilone
Accession Number
DB12391  (DB05654)
Type
Small Molecule
Groups
Investigational
Description

Sagopilone has been used in trials studying the treatment of Melanoma, Neoplasms, CNS Disease, Breast Cancer, and Breast Neoplasms, among others. It is a so-called fully synthetic epothilone and is the first such compound to be in clinical development to combat several forms of cancer. Epothilones are 16-member ring macrolides with antimicrotubule activity that share a similar mechanism of action to the taxanes but have demonstrated potent antiproliferative activity in several different multidrug-resistant and paclitaxel-resistant tumor cell lines in vitro and in vivo.

Structure
Thumb
Synonyms
Not Available
External IDs
BAY86-5302 / DE-03757 / ZK 219477 / ZK-219477 / ZK-EPO
Categories
UNII
KY72JU32FO
CAS number
305841-29-6
Weight
Average: 543.72
Monoisotopic: 543.265459218
Chemical Formula
C30H41NO6S
InChI Key
BFZKMNSQCNVFGM-UCEYFQQTSA-N
InChI
InChI=1S/C30H41NO6S/c1-7-9-20-27(34)17(2)10-8-13-30(6)25(37-30)15-22(19-11-12-23-21(14-19)31-18(3)38-23)36-26(33)16-24(32)29(4,5)28(20)35/h7,11-12,14,17,20,22,24-25,27,32,34H,1,8-10,13,15-16H2,2-6H3/t17-,20+,22-,24-,25-,27-,30+/m0/s1
IUPAC Name
(1S,3S,7S,10R,11S,12S,16R)-7,11-dihydroxy-8,8,12,16-tetramethyl-3-(2-methyl-1,3-benzothiazol-5-yl)-10-(prop-2-en-1-yl)-4,17-dioxabicyclo[14.1.0]heptadecane-5,9-dione
SMILES
C[C@H]1CCC[C@@]2(C)O[C@H]2C[C@H](OC(=O)C[C@H](O)C(C)(C)C(=O)[C@H](CC=C)[C@H]1O)C1=CC=C2SC(C)=NC2=C1

Pharmacology

Indication
Not Available
Pharmacodynamics

Sagopilone is a highly potent, fully synthetic epothilone that was specifically designed to be safer and more effective than other chemotherapy drugs like paclitaxel and other epothilones for the treatment of solid tumor cancers. In early phase studies, Sagopilone appears to have greater antitumor activity relative to other epothilones, and appears to cross the blood-brain barrier which may help to treat brain tumors or metastases.

Mechanism of action

Epothilones are a new class of cytotoxic agents that induce tubulin polymerization. Sagopilone, the only fully synthetic, third-generation analogue of epothilone B, is a highly potent tubulin stabilizer that has shown substantial preclinical antitumor activity, including against taxane-resistant models.

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
DrugInteraction
(R)-warfarinThe serum concentration of (R)-warfarin can be increased when it is combined with Sagopilone.
(S)-WarfarinThe serum concentration of (S)-Warfarin can be increased when it is combined with Sagopilone.
3-isobutyl-1-methyl-7H-xanthineThe metabolism of 3-isobutyl-1-methyl-7H-xanthine can be decreased when combined with Sagopilone.
4-hydroxycoumarinThe metabolism of 4-hydroxycoumarin can be decreased when combined with Sagopilone.
6-O-benzylguanineThe metabolism of 6-O-benzylguanine can be decreased when combined with Sagopilone.
7-DeazaguanineThe metabolism of 7-Deazaguanine can be decreased when combined with Sagopilone.
7,9-DimethylguanineThe metabolism of 7,9-Dimethylguanine can be decreased when combined with Sagopilone.
8-azaguanineThe metabolism of 8-azaguanine can be decreased when combined with Sagopilone.
8-chlorotheophyllineThe metabolism of 8-chlorotheophylline can be decreased when combined with Sagopilone.
9-DeazaguanineThe metabolism of 9-Deazaguanine can be decreased when combined with Sagopilone.
Additional Data Available
  • Extended Description
    Extended Description

    Extended description of the mechanism of action and particular properties of each drug interaction.

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  • Severity
    Severity

    A severity rating for each drug interaction, from minor to major.

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  • Evidence Level
    Evidence Level

    A rating for the strength of the evidence supporting each drug interaction.

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  • Action
    Action

    An effect category for each drug interaction. Know how this interaction affects the subject drug.

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Food Interactions
Not Available

References

General References
  1. Fumoleau P, Coudert B, Isambert N, Ferrant E: Novel tubulin-targeting agents: anticancer activity and pharmacologic profile of epothilones and related analogues. Ann Oncol. 2007 Jul;18 Suppl 5:v9-15. [PubMed:17656562]
  2. Cortes J, Baselga J: Targeting the microtubules in breast cancer beyond taxanes: the epothilones. Oncologist. 2007 Mar;12(3):271-80. [PubMed:17405891]
  3. Klar U, Buchmann B, Schwede W, Skuballa W, Hoffmann J, Lichtner RB: Total synthesis and antitumor activity of ZK-EPO: the first fully synthetic epothilone in clinical development. Angew Chem Int Ed Engl. 2006 Dec 4;45(47):7942-8. [PubMed:17006870]
  4. Larkin JM, Kaye SB: Epothilones in the treatment of cancer. Expert Opin Investig Drugs. 2006 Jun;15(6):691-702. [PubMed:16732719]
External Links
PubChem Compound
11284169
PubChem Substance
347828638
ChemSpider
9459163
ChEMBL
CHEMBL2304041

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedTreatmentNeoplasms1
1, 2CompletedTreatmentCarcinoma, Small Cell1
2CompletedTreatmentBrain and Central Nervous System Tumors1
2CompletedTreatmentBreast Cancer, Metastatic / Neoplasms, Breast1
2CompletedTreatmentGlioblastomas1
2CompletedTreatmentMelanoma1
2CompletedTreatmentNeoplasms, Breast1
2CompletedTreatmentNeoplasms, Ovarian1
2CompletedTreatmentNon Small Cell Lung Carcinoma (NSCLC)1
2TerminatedTreatmentCancer, Breast / CNS Disease1
2TerminatedTreatmentSmall Cell Lung Carcinoma1

Pharmacoeconomics

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

Properties

State
Not Available
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.0024 mg/mLALOGPS
logP4.42ALOGPS
logP5.1ChemAxon
logS-5.4ALOGPS
pKa (Strongest Acidic)14.08ChemAxon
pKa (Strongest Basic)2.88ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count6ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area109.25 Å2ChemAxon
Rotatable Bond Count3ChemAxon
Refractivity145.71 m3·mol-1ChemAxon
Polarizability59.69 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability0ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
Not Available

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 macrolides and analogues. These are organic compounds containing a lactone ring of at least twelve members.
Kingdom
Organic compounds
Super Class
Phenylpropanoids and polyketides
Class
Macrolides and analogues
Sub Class
Not Available
Direct Parent
Macrolides and analogues
Alternative Parents
Benzothiazoles / Benzenoids / Thiazoles / Heteroaromatic compounds / Secondary alcohols / Lactones / Carboxylic acid esters / Cyclic ketones / Oxacyclic compounds / Azacyclic compounds
show 7 more
Substituents
Macrolide / 1,3-benzothiazole / Benzenoid / Azole / Heteroaromatic compound / Thiazole / Carboxylic acid ester / Ketone / Lactone / Secondary alcohol
show 19 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
Not Available

Enzymes

Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Inhibitor
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
References
  1. Kuper JI, D'Aprile M: Drug-Drug interactions of clinical significance in the treatment of patients with Mycobacterium avium complex disease. Clin Pharmacokinet. 2000 Sep;39(3):203-14. [PubMed:11020135]

Drug created on October 20, 2016 16:11 / Updated on June 04, 2019 07:37