NAV

KOS-1584

Identification

Generic Name
KOS-1584
DrugBank Accession Number
DB05903
Background

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
3D
Similar Structures
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
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Pharmacology

Indication

Investigated for use/treatment in solid tumors.

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Contraindications & Blackbox Warnings
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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
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Toxicity

Not Available

Pathways
Not Available
Pharmacogenomic Effects/ADRs Browse all" title="About SNP Mediated Effects/ADRs" id="snp-actions-info" class="drug-info-popup" href="javascript:void(0);">
Not Available

Interactions

Drug Interactions Learn More" title="About Drug Interactions" id="structured-interactions-info" class="drug-info-popup" href="javascript:void(0);">
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
Integrate drug-drug
interactions in your software
AbemaciclibThe serum concentration of Abemaciclib can be increased when it is combined with KOS-1584.
AcalabrutinibThe serum concentration of Acalabrutinib can be increased when it is 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.
Food Interactions
Not Available

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
Affected organisms
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[C@H]1\C=C\C\C(C)=C/C[C@H](OC(=O)C[C@H](O)C(C)(C)C(=O)[C@H](C)[C@H]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. [Article]
  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. [Article]
PubChem Compound
6918835
PubChem Substance
347827748
ChemSpider
5294026
ZINC
ZINC000100657972

Clinical Trials

Clinical Trials Learn More" title="About Clinical Trials" id="clinical-trials-info" class="drug-info-popup" href="javascript:void(0);">
PhaseStatusPurposeConditionsCount
2CompletedTreatmentNon-Small Cell Lung 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)14.07Chemaxon
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-MSsplash10-00di-3501900000-78b8338c3607bcda943d
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSsplash10-0uk9-0000900000-402dc8b8a340801d8fec
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSsplash10-000i-0000900000-97908171e2ed54b28423
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSsplash10-0080-1203900000-cae6f16e5d15172c1c0c
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSsplash10-0udi-1400900000-77c1429e380dd5813c83
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSsplash10-00di-9502300000-49d02c2275bb9410a4d7
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSsplash10-0006-5902300000-55f3ef5bd5a188f78beb
Predicted 1H NMR Spectrum1D NMRNot Applicable
Predicted 13C NMR Spectrum1D NMRNot Applicable
Chromatographic Properties
Collision Cross Sections (CCS)
AdductCCS Value (Å2)Source typeSource
[M-H]-228.32292
predicted
DeepCCS 1.0 (2019)
[M+H]+230.21834
predicted
DeepCCS 1.0 (2019)
[M+Na]+235.89807
predicted
DeepCCS 1.0 (2019)

Enzymes

Details1. Cytochrome P450 3A4
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. [Article]

Drug created at November 18, 2007 18:28 / Updated at June 12, 2020 16:52