KOS-1584

Identification

Name
KOS-1584
Accession Number
DB05903
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.

Type
Small Molecule
Groups
Investigational
Structure
Thumb
Weight
Average: 489.67
Monoisotopic: 489.254894534
Chemical Formula
C27H39NO5S
Synonyms
  • (E)-9,10-Dehydroepothilone D
  • (E)-9,10-Didehydroepothilone D
External IDs
  • KOS-1584
  • R 1645
  • R-1645
  • R1645

Pharmacology

Indication

Investigated for use/treatment in solid tumors.

Contraindications & Blackbox Warnings
Learn about our commercial Contraindications & Blackbox Warnings data.
Learn More
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
Adverse Effects
Learn about our commercial Adverse Effects data.
Learn More
Toxicity
Not Available
Affected organisms
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.
DrugInteraction
AbirateroneThe metabolism of Abiraterone can be decreased when combined with KOS-1584.
AcalabrutinibThe metabolism of Acalabrutinib can be decreased when combined with KOS-1584.
AcenocoumarolThe serum concentration of Acenocoumarol can be increased when it is combined with KOS-1584.
AcetyldigitoxinThe serum concentration of Acetyldigitoxin can be increased when it is combined with KOS-1584.
AlbendazoleThe metabolism of Albendazole can be decreased when combined with KOS-1584.
AlectinibThe metabolism of Alectinib can be decreased when combined with KOS-1584.
AlfentanilThe serum concentration of Alfentanil can be increased when it is combined with KOS-1584.
AlfuzosinThe metabolism of Alfuzosin can be decreased when combined with KOS-1584.
AlpelisibThe metabolism of Alpelisib can be decreased when combined with KOS-1584.
AlprazolamThe metabolism of Alprazolam can be decreased when combined with KOS-1584.
Additional Data Available
  • Extended Description
    Extended Description

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

    Learn more
  • Severity
    Severity

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

    Learn more
  • Evidence Level
    Evidence Level

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

    Learn more
  • Action
    Action

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

    Learn more
Food Interactions
Not Available

Products

Categories

Drug Categories
Chemical TaxonomyProvided by Classyfire
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
2,4-disubstituted 1,3-thiazole / Alcohol / Aromatic heteromonocyclic compound / Azacycle / Azole / Carbonyl group / Carboxylic acid derivative / Carboxylic acid ester / Cyclic ketone / Heteroaromatic compound
show 14 more
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
Not Available

Chemical Identifiers

UNII
82481G197K
CAS number
350493-61-7
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

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]
PubChem Compound
6918835
PubChem Substance
347827748
ChemSpider
5294026
ZINC
ZINC000100657972

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
2CompletedTreatmentNon-Small Cell Lung Carcinoma (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)14.07ChemAxon
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
Polarizability54.41 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

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. doi: 10.2165/00003088-200039030-00003. [PubMed:11020135]

Drug created on November 18, 2007 11:28 / Updated on June 12, 2020 10:52

Logo pink
Are you a
new drug developer?
Contact us to learn more about our customized products and solutions.
Logo pink
Stay in the know!
As part of our commitment to providing the most up-to-date drug information, we will be releasing #DrugBankUpdates with our newly added curated drug pages.
#DrugBankUpdates