NAV

Elacytarabine

Identification

创eric Name
Elacytarabine
DrugBank Accession Number
DB05494
Background

Elacytarabine is a fatty acid derivative of阿糖胞苷, an approved cytotoxic cancer drug. Cytarabine has limitations such as minimal uptake in solid tumours and is only used to treat leukaemia. Elacytarabine is designed to overcome this limitation and has shown considerable uptake in solid tumour cells. Elacytarabine is a patented new chemical entity of the nucleoside analog class, with improved biological properties and the potential to treat solid tumours such as non-small cell lung cancer, malignant melanoma and ovarian cancer.

Type
Small Molecule
Groups
Investigational
Structure
MOL SDF PDB SMILES InChI
Similar Structures
Weight
Average: 507.672
Monoisotopic: 507.330836181
Chemical Formula
C27H45N3O6
Synonyms
  • Elacytarabine
External IDs
  • CP 4055
  • CP-4055
  • P-4055

Pharmacology

Indication

Investigated for use/treatment in leukemia (unspecified) and melanoma.

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Contraindications & Blackbox Warnings
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Pharmacodynamics

cp - 4055是阿糖胞苷的脂肪酸衍生物,an approved cytotoxic cancer drug. Cytarabine has limitations such as minimal uptake in solid tumours and is only used to treat leukaemia. CP-4055 is designed to overcome this limitation and has shown considerable uptake in solid tumour cells. CP-4055 is a patented new chemical entity of the nucleoside analog class, with improved biological properties and the potential to treat solid tumours such as non-small cell lung cancer, malignant melanoma and ovarian cancer.

Mechanism of action

CP-4055 is the lipophilic 5'-elaidic acid ester of the deoxycytidine analog cytosine arabinoside (cytarabine; Ara-C) with potential antineoplastic activity. As a prodrug, CP-4055 is converted intracellularly into cytarabine triphosphate by deoxycytidine kinase and subsequently competes with cytidine for incorporation into DNA, thereby inhibiting DNA synthesis. Compared to cytarabine, CP-4055 shows increased cellular uptake and retention, resulting in increased activation by deoxycytidine kinase to cytarabine triphosphate, decreased deamination and deactivation by deoxycytidine deaminase, and increased inhibition of DNA synthesis. This agent also inhibits RNA synthesis, an effect not seen with cytarabine.

Target Actions Organism
UDeoxycytidine kinase Not Available Humans
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/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.
Not Available
Food Interactions
Not Available

Categories

Drug Categories
Chemical TaxonomyProvided byClassyfire
Description
This compound belongs to the class of organic compounds known as pyrimidine nucleosides. These are compounds comprising a pyrimidine base attached to a ribosyl or deoxyribosyl moiety.
Kingdom
Organic compounds
Super Class
Nucleosides, nucleotides, and analogues
Class
Pyrimidine nucleosides
Sub Class
Not Available
Direct Parent
Pyrimidine nucleosides
Alternative Parents
Glycosylamines/Pentoses/Aminopyrimidines and derivatives/Pyrimidones/Fatty acid esters/Hydropyrimidines/Imidolactams/Tetrahydrofurans/Heteroaromatic compounds/1,2-diols
show 11 more
Substituents
1,2-diol/Alcohol/Amine/Amino acid or derivatives/Aminopyrimidine/Aromatic heteromonocyclic compound/Azacycle/Carbonyl group/Carboxylic acid derivative/Carboxylic acid ester
show 25 more
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
Not Available
Affected organisms
Not Available

Chemical Identifiers

UNII
TA7WJG93AR
CAS number
188181-42-2
InChI Key
FLFGNMFWNBOBGE-FNNZEKJRSA-N
InChI
InChI=1S/C27H45N3O6/c1-2-3-4-5-6-7-8-9-10-11-12-13-14-15-16-17-23(31)35-20-21-24(32)25(33)26(36-21)30-19-18-22(28)29-27(30)34/h9-10,18-19,21,24-26,32-33H,2-8,11-17,20H2,1H3,(H2,28,29,34)/b10-9+/t21-,24-,25+,26-/m1/s1
IUPAC Name
[(2R,3S,4S,5R)-5-(4-amino-2-oxo-1,2-dihydropyrimidin-1-yl)-3,4-dihydroxyoxolan-2-yl]methyl (9E)-octadec-9-enoate
SMILES
CCCCCCCC\C=C\CCCCCCCC(=O)OC[C@H]1O[C@H]([C@@H](O)[C@@H]1O)N1C=CC(N)=NC1=O

References

创eral References
  1. Bergman AM, Kuiper CM, Voorn DA, Comijn EM, Myhren F, Sandvold ML, Hendriks HR, Peters GJ: Antiproliferative activity and mechanism of action of fatty acid derivatives of arabinofuranosylcytosine in leukemia and solid tumor cell lines. Biochem Pharmacol. 2004 Feb 1;67(3):503-11. [Article]
PubChem Compound
6438895
PubChem Substance
175427021
ChemSpider
4943338
BindingDB
50004746
ChEMBL
CHEMBL2105665

Clinical Trials

Clinical TrialsLearn More" title="" id="clinical-trials-info" class="drug-info-popup" href="javascript:void(0);">
Phase Status Purpose Conditions Count
3 Completed Treatment Acute Myeloid Leukemia (AML) 1
2 Completed Treatment Acute Myeloid Leukemia (AML) 1
2 Completed Treatment Advanced Colorectal Cancer/Colorectal Cancer 1
2 Completed Treatment Melanoma, Malignant 1
2 Completed Treatment Melanoma, Malignant/Neoplasms, Metastasis 1
1 Completed Basic Science Not Applicable as This is a Mass Balance/Pharmacokinetic Study Performed in Healthy Subjects 1
1 Completed Treatment Relapsed/Refractory AML 1
1, 2 Completed Treatment Acute Myeloid Leukemia (AML)/Malignancies, Hematologic 1
1, 2 Completed Treatment Ovarian Cancer 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 0.00419 mg/mL ALOGPS
logP 5.52 ALOGPS
logP 4.65 ChemAxon
logS -5.1 ALOGPS
pKa (Strongest Acidic) 12.56 ChemAxon
pKa (Strongest Basic) 4.07 ChemAxon
Physiological Charge 0 ChemAxon
Hydrogen Acceptor Count 7 ChemAxon
Hydrogen Donor Count 3 ChemAxon
Polar Surface Area 134.68 Å2 ChemAxon
Rotatable Bond Count 19 ChemAxon
Refractivity 138.45 m3·mol-1 ChemAxon
Polarizability 59.02 Å3 ChemAxon
Number of Rings 2 ChemAxon
Bioavailability 0 ChemAxon
Rule of Five No ChemAxon
Ghose Filter No ChemAxon
Veber's Rule No ChemAxon
MDDR-like Rule No ChemAxon
Predicted ADMET Features
Property Value Probability
Human Intestinal Absorption + 0.9623
Blood Brain Barrier + 0.9465
Caco-2 permeable - 0.8887
P-glycoprotein substrate Non-substrate 0.798
P-glycoprotein inhibitor I Non-inhibitor 0.9686
P-glycoprotein inhibitor II Non-inhibitor 0.9532
Renal organic cation transporter Non-inhibitor 0.9519
CYP450 2C9 substrate Non-substrate 0.793
CYP450 2D6 substrate Non-substrate 0.8613
CYP450 3A4 substrate Non-substrate 0.6203
CYP450 1A2 substrate Non-inhibitor 0.9543
CYP450 2C9 inhibitor Non-inhibitor 0.9638
CYP450 2D6 inhibitor Non-inhibitor 0.9497
CYP450 2C19 inhibitor Non-inhibitor 0.9489
CYP450 3A4 inhibitor Non-inhibitor 0.9609
CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.981
Ames test Non AMES toxic 0.9132
Carcinogenicity Non-carcinogens 0.9158
Biodegradation Not ready biodegradable 0.7807
Rat acute toxicity 1.7184 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Weak inhibitor 0.983
hERG inhibition (predictor II) Non-inhibitor 0.911
ADMET data is predicted usingadmetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
Spectrum Spectrum Type Splash Key
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

Targets

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Details 1.Deoxycytidine kinase
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
创eral Function
Protein homodimerization activity
Specific Function
Required for the phosphorylation of the deoxyribonucleosides deoxycytidine (dC), deoxyguanosine (dG) and deoxyadenosine (dA). Has broad substrate specificity, and does not display selectivity based...
创e Name
DCK
Uniprot ID
P27707
Uniprot Name
Deoxycytidine kinase
分子量
30518.315 Da

Drug created at November 18, 2007 18:25 / Updated at February 21, 2021 18:51