Elacytarabine

Identification

Name
Elacytarabine
Accession Number
DB05494
Type
Small Molecule
Groups
Investigational
Description

Elacytarabine is a fatty acid derivative of cytarabine, 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.

Structure
Thumb
Synonyms
Not Available
External IDs
CP 4055 / CP-4055 / P-4055
International/Other Brands
Elacyt
Categories
UNII
TA7WJG93AR
CAS number
188181-42-2
Weight
Average: 507.672
Monoisotopic: 507.330836181
Chemical Formula
C27H45N3O6
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)-3,4-dihydroxy-5-(2-hydroxy-4-imino-1,4-dihydropyrimidin-1-yl)oxolan-2-yl]methyl (9E)-octadec-9-enoate
SMILES
[H]\C(CCCCCCCC)=C(\[H])CCCCCCCC(=O)OC[C@@]1([H])O[C@@]([H])(N2C=CC(=N)N=C2O)[C@@]([H])(O)[C@]1([H])O

Pharmacology

Indication

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

Pharmacodynamics

CP-4055 is a fatty acid derivative of cytarabine, 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.

TargetActionsOrganism
UDeoxycytidine kinaseNot AvailableHuman
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
Not Available
Food Interactions
Not Available

References

General 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. [PubMed:15037202]
External Links
PubChem Compound
6438895
PubChem Substance
175427021
ChemSpider
4943338
BindingDB
50004746
ChEMBL
CHEMBL2105665

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedBasic ScienceNot Applicable as This is a Mass Balance/Pharmacokinetic Study Performed in Healthy Subjects1
1CompletedTreatmentRelapsed/Refractory AML1
1, 2CompletedTreatmentCancer of the Ovary1
1, 2CompletedTreatmentLeukemia Acute Myeloid Leukemia (AML) / Malignancies, Hematologic1
2CompletedTreatmentAdvanced Colorectal Cancer / Colorectal Cancers1
2CompletedTreatmentMalignant Melanoma1
2CompletedTreatmentMalignant Melanoma / Neoplasms Metastasis1
3CompletedTreatmentLeukemia Acute Myeloid Leukemia (AML)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 Solubility0.00304 mg/mLALOGPS
logP5.44ALOGPS
logP5.63ChemAxon
logS-5.2ALOGPS
pKa (Strongest Acidic)5.72ChemAxon
pKa (Strongest Basic)2.37ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count8ChemAxon
Hydrogen Donor Count4ChemAxon
Polar Surface Area135.67 Å2ChemAxon
Rotatable Bond Count19ChemAxon
Refractivity149.87 m3·mol-1ChemAxon
Polarizability59.41 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability0ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9623
Blood Brain Barrier+0.9465
Caco-2 permeable-0.8887
P-glycoprotein substrateNon-substrate0.798
P-glycoprotein inhibitor INon-inhibitor0.9686
P-glycoprotein inhibitor IINon-inhibitor0.9532
Renal organic cation transporterNon-inhibitor0.9519
CYP450 2C9 substrateNon-substrate0.793
CYP450 2D6 substrateNon-substrate0.8613
CYP450 3A4 substrateNon-substrate0.6203
CYP450 1A2 substrateNon-inhibitor0.9543
CYP450 2C9 inhibitorNon-inhibitor0.9638
CYP450 2D6 inhibitorNon-inhibitor0.9497
CYP450 2C19 inhibitorNon-inhibitor0.9489
CYP450 3A4 inhibitorNon-inhibitor0.9609
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.981
Ames testNon AMES toxic0.9132
CarcinogenicityNon-carcinogens0.9158
BiodegradationNot ready biodegradable0.7807
Rat acute toxicity1.7184 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.983
hERG inhibition (predictor II)Non-inhibitor0.911
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
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 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
Pyrimidine nucleoside / Glycosyl compound / N-glycosyl compound / Pentose monosaccharide / Aminopyrimidine / Fatty acid ester / Pyrimidone / Hydropyrimidine / Monosaccharide / Fatty acyl
show 25 more
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
Not Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
Unknown
General 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...
Gene Name
DCK
Uniprot ID
P27707
Uniprot Name
Deoxycytidine kinase
Molecular Weight
30518.315 Da

Drug created on November 18, 2007 11:25 / Updated on October 01, 2018 14:01