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
-
结构为科斯- 1584 (DB05903)
- 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.
Reduce drug development failure ratesBuild, train, & validate machine-learning models
with evidence-based and structured datasets.Build, train, & validate predictive machine-learning models with structured datasets. - Contraindications & Blackbox Warnings
-
Avoid life-threatening adverse drug eventsImprove clinical decision support with information oncontraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events & improve clinical decision support. - 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
-
Improve decision support & research outcomesWith structured adverse effects data, including:blackbox warnings, adverse reactions, warning & precautions, & incidence rates.Improve decision support & research outcomes with our structured adverse effects data. - Toxicity
-
Not Available
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRsBrowse all" title="" id="snp-actions-info" class="drug-info-popup" href="javascript:void(0);">
- Not Available
Interactions
- Drug InteractionsLearn More" title="" 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.
Drug Interaction Integrate drug-drug
interactions in your softwareAbemaciclib The metabolism of Abemaciclib can be decreased when combined with KOS-1584. Acalabrutinib The metabolism of Acalabrutinib can be decreased when combined with KOS-1584. Acenocoumarol The serum concentration of Acenocoumarol can be increased when it is combined with KOS-1584. Acetyldigitoxin The serum concentration of Acetyldigitoxin can be increased when it is combined with KOS-1584. 阿苯达唑 The metabolism of Albendazole can be decreased when combined with KOS-1584. Alectinib The metabolism of Alectinib can be decreased when combined with KOS-1584. Alfentanil The serum concentration of Alfentanil can be increased when it is combined with KOS-1584. Alfuzosin The metabolism of Alfuzosin can be decreased when combined with KOS-1584. Alpelisib The metabolism of Alpelisib can be decreased when combined with KOS-1584. Alprazolam The serum concentration of Alprazolam can be increased when it is combined with KOS-1584. 
Identify potential medication risksEasily compare up to 40 drugs with our drug interaction checker.Get severity rating, description, and management advice.Learn more - Food Interactions
- Not Available
Categories
- Drug Categories
- Chemical TaxonomyProvided byClassyfire
-
- 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
- 82481 g197k
- 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@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
参考文献
- General References
-
- Pronzato P: New therapeutic options for chemotherapy-resistant metastatic breast cancer: the epothilones. Drugs. 2008;68(2):139-46. [Article]
- 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]
- External Links
-
- PubChem Compound
- 6918835
- PubChem Substance
- 347827748
- ChemSpider
- 5294026
- ZINC
- ZINC000100657972
Clinical Trials
- Clinical TrialsLearn More" title="" id="clinical-trials-info" class="drug-info-popup" href="javascript:void(0);">
-
Phase Status Purpose Conditions Count 2 Completed 治疗 Non-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
-
Property Value Source Water Solubility 0.00256 mg/mL ALOGPS logP 4.31 ALOGPS logP 4.73 Chemaxon logS -5.3 ALOGPS pKa (Strongest Acidic) 14.07 Chemaxon pKa (Strongest Basic) 2.73 Chemaxon Physiological Charge 0 Chemaxon Hydrogen Acceptor Count 5 Chemaxon Hydrogen Donor Count 2 Chemaxon Polar Surface Area 96.72 Å2 Chemaxon Rotatable Bond Count 2 Chemaxon Refractivity 137.16 m3·mol-1 Chemaxon Polarizability 54.41 Å3 Chemaxon Number of Rings 2 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter No Chemaxon Veber's Rule No Chemaxon MDDR-like Rule No Chemaxon - Predicted ADMET Features
- Not Available
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
-
Spectrum Spectrum Type Splash Key Predicted GC-MS Spectrum - GC-MS Predicted GC-MS Not Available Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS 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
参考文献
- 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