KOS-1584

Identification

Name
KOS-1584
Accession Number
DB05903
Type
Small Molecule
Groups
Investigational
Description

KOS-1584 is a second-generation epothilone. Epothilones are anticancer agents with a taxane-like mechanism of action that have demonstrated activity in taxane-resistant tumors. KOS-1584 is a second-generation compound with increased potency, favorable tissue distribution, and ease of formulation.

Structure
Thumb
Synonyms
Not Available
External IDs
R1645
Categories
UNII
82481G197K
CAS number
Not Available
Weight
Average: 489.67
Monoisotopic: 489.254894534
Chemical Formula
C27H39NO5S
InChI Key
XAYAKDZVINDZGB-BMVMHAJPSA-N
InChI
InChI=1S/C27H39NO5S/c1-16-9-8-10-17(2)25(31)19(4)26(32)27(6,7)23(29)14-24(30)33-22(12-11-16)18(3)13-21-15-34-20(5)28-21/h8,10-11,13,15,17,19,22-23,25,29,31H,9,12,14H2,1-7H3/b10-8+,16-11-,18-13+/t17-,19+,22-,23-,25-/m0/s1
IUPAC Name
(4S,7R,8S,9S,10E,13Z,16S)-4,8-dihydroxy-5,5,7,9,13-pentamethyl-16-[(1E)-1-(2-methyl-1,3-thiazol-4-yl)prop-1-en-2-yl]-1-oxacyclohexadeca-10,13-diene-2,6-dione
SMILES
C[[email protected]]1\C=C\C\C(C)=C/C[[email protected]](OC(=O)C[[email protected]](O)C(C)(C)C(=O)[[email protected]](C)[[email protected]]1O)C(\C)=C\C1=CSC(C)=N1

Pharmacology

Indication

Investigated for use/treatment in solid tumors.

Structured Indications
Not Available
Pharmacodynamics
Not Available
Mechanism of action

Epothilones are highly potent microtubulin stabilizing compounds with a similar mechanism of action to taxanes and broad applicability in a wide range of tumors. Epothilones are active in both taxane-sensitive and taxane-resistant cancers and have demonstrated low susceptibility to tumor resistance mechanisms.

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
DrugInteractionDrug group
AcetyldigitoxinAcetyldigitoxin may decrease the cardiotoxic activities of KOS-1584.Approved
AcetyldigoxinAcetyldigoxin may decrease the cardiotoxic activities of KOS-1584.Experimental
BevacizumabBevacizumab may increase the cardiotoxic activities of KOS-1584.Approved, Investigational
CabazitaxelThe risk or severity of adverse effects can be increased when Cabazitaxel is combined with KOS-1584.Approved
CyclophosphamideCyclophosphamide may increase the cardiotoxic activities of KOS-1584.Approved, Investigational
CymarinCymarin may decrease the cardiotoxic activities of KOS-1584.Experimental
DeslanosideDeslanoside may decrease the cardiotoxic activities of KOS-1584.Approved
DigitoxinDigitoxin may decrease the cardiotoxic activities of KOS-1584.Approved, Investigational
DigoxinDigoxin may decrease the cardiotoxic activities of KOS-1584.Approved
DocetaxelThe risk or severity of adverse effects can be increased when Docetaxel is combined with KOS-1584.Approved, Investigational
GitoformateGitoformate may decrease the cardiotoxic activities of KOS-1584.Experimental
Lanatoside CLanatoside C may decrease the cardiotoxic activities of KOS-1584.Experimental
MetildigoxinMetildigoxin may decrease the cardiotoxic activities of KOS-1584.Experimental
OleandrinOleandrin may decrease the cardiotoxic activities of KOS-1584.Experimental, Investigational
OuabainOuabain may decrease the cardiotoxic activities of KOS-1584.Approved
PaclitaxelThe risk or severity of adverse effects can be increased when Paclitaxel is combined with KOS-1584.Approved, Vet Approved
PeruvosidePeruvoside may decrease the cardiotoxic activities of KOS-1584.Experimental
ProscillaridinProscillaridin may decrease the cardiotoxic activities of KOS-1584.Experimental
TrastuzumabTrastuzumab may increase the cardiotoxic activities of KOS-1584.Approved, Investigational
Food Interactions
Not Available

References

General References
  1. Pronzato P: New therapeutic options for chemotherapy-resistant metastatic breast cancer: the epothilones. Drugs. 2008;68(2):139-46. [PubMed:18197722]
  2. 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]
External Links
PubChem Compound
6918835
PubChem Substance
347827748
ChemSpider
5294026

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
2CompletedTreatmentLung 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 Solubility0.00256 mg/mLALOGPS
logP4.31ALOGPS
logP4.73ChemAxon
logS-5.3ALOGPS
pKa (Strongest Acidic)14.06ChemAxon
pKa (Strongest Basic)2.73ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count5ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area96.72 Å2ChemAxon
Rotatable Bond Count2ChemAxon
Refractivity137.16 m3·mol-1ChemAxon
Polarizability53.73 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
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
2,4-disubstituted thiazoles / Heteroaromatic compounds / Secondary alcohols / Lactones / Cyclic ketones / Carboxylic acid esters / Oxacyclic compounds / Monocarboxylic acids and derivatives / Azacyclic compounds / Organonitrogen compounds
show 2 more
Substituents
Macrolide / 2,4-disubstituted 1,3-thiazole / Azole / Heteroaromatic compound / Thiazole / Carboxylic acid ester / Ketone / Lactone / Secondary alcohol / Cyclic ketone
show 14 more
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
Not Available

Drug created on November 18, 2007 11:28 / Updated on November 09, 2017 03:52