Identification

Name
Eflornithine
Accession Number
DB06243
Type
Small Molecule
Groups
Approved, Withdrawn
Description

Eflornithine is a prescription drug indicated in the treatment of facial hirsutism (excessive hair growth). Eflornithine hydrochloride cream for topical application is intended for use in women suffering from facial hirsutism and is sold by Allergan, Inc. under the brand name Vaniqa. Besides being a non-mechanical and non-cosmetic treatment, eflornithine is the only non-hormonal and non-systemic prescription option available for women who suffer from facial hirsutism. Eflornithine for injection against sleeping sickness was manufactured by Sanofi Aventis and sold under the brand name Ornidyl in the USA. It is now discontinued. Eflornithine is on the World Health Organization's List of Essential Medicines.

Structure
Thumb
Synonyms
  • (RS)-2,5-diamino-2-(difluoromethyl)pentanoic acid
  • 2-(difluoromethyl)ornithine
  • alpha-difluoromethylornithine
  • DFMO
  • α-difluoromethylornithine
External IDs
BRN 2250529 / HSDB 7923 / MDL 71782 / RFI 7178 / RMI 71782
Product Ingredients
IngredientUNIICASInChI Key
Eflornithine hydrochloride4NH22NDW9H96020-91-6FJPAMFNRCFEGSD-UHFFFAOYSA-N
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
VaniqaCream139 mg/gTopicalPhysicians Total Care, Inc.2004-07-26Not applicableUs
VaniqaCream13.9 %TopicalCipher Pharmaceuticals Inc.2005-11-01Not applicableCanada
VaniqaCream139 mg/gTopicalAllergan2013-06-01Not applicableUs
Categories
UNII
ZQN1G5V6SR
CAS number
70052-12-9
Weight
Average: 182.171
Monoisotopic: 182.08668396
Chemical Formula
C6H12F2N2O2
InChI Key
VLCYCQAOQCDTCN-UHFFFAOYSA-N
InChI
InChI=1S/C6H12F2N2O2/c7-4(8)6(10,5(11)12)2-1-3-9/h4H,1-3,9-10H2,(H,11,12)
IUPAC Name
2,5-diamino-2-(difluoromethyl)pentanoic acid
SMILES
NCCCC(N)(C(F)F)C(O)=O

Pharmacology

Indication

Eflornithine is indicated in the treatment of facial hirsutism (excessive hair growth).

Structured Indications
Pharmacodynamics
Not Available
Mechanism of action

Eflornithine prevents hair growth by inhibiting the anagen phase of hair production. This occurs by eflornithine irreversibly binding (also called suicide inhibition) to ornithine decarboxylase (ODC) and physically preventing the natural substrate ornithine from accessing the active site.

TargetActionsOrganism
AOrnithine decarboxylase
antagonist
blocker
Human
Absorption
Not Available
Volume of distribution
Not Available
Protein binding
Not Available
Metabolism

Not metabolized

Route of elimination

Renal

Half life

8 hours

Clearance
Not Available
Toxicity
Not Available
Affected organisms
  • Humans and other mammals
  • Yeast, Molds, Trypanosomes
  • Trypanosoma brucei gambiense
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteractionDrug group
AcetyldigitoxinAcetyldigitoxin may decrease the cardiotoxic activities of Eflornithine.Approved
AcetyldigoxinAcetyldigoxin may decrease the cardiotoxic activities of Eflornithine.Experimental
BevacizumabBevacizumab may increase the cardiotoxic activities of Eflornithine.Approved, Investigational
CabazitaxelThe risk or severity of adverse effects can be increased when Cabazitaxel is combined with Eflornithine.Approved
CyclophosphamideCyclophosphamide may increase the cardiotoxic activities of Eflornithine.Approved, Investigational
CymarinCymarin may decrease the cardiotoxic activities of Eflornithine.Experimental
DeslanosideDeslanoside may decrease the cardiotoxic activities of Eflornithine.Approved
DigitoxinDigitoxin may decrease the cardiotoxic activities of Eflornithine.Approved, Investigational
DigoxinDigoxin may decrease the cardiotoxic activities of Eflornithine.Approved
DocetaxelThe risk or severity of adverse effects can be increased when Docetaxel is combined with Eflornithine.Approved, Investigational
GitoformateGitoformate may decrease the cardiotoxic activities of Eflornithine.Experimental
Lanatoside CLanatoside C may decrease the cardiotoxic activities of Eflornithine.Experimental
MetildigoxinMetildigoxin may decrease the cardiotoxic activities of Eflornithine.Experimental
OleandrinOleandrin may decrease the cardiotoxic activities of Eflornithine.Experimental, Investigational
OuabainOuabain may decrease the cardiotoxic activities of Eflornithine.Approved
PaclitaxelThe risk or severity of adverse effects can be increased when Paclitaxel is combined with Eflornithine.Approved, Vet Approved
PeruvosidePeruvoside may decrease the cardiotoxic activities of Eflornithine.Experimental
ProscillaridinProscillaridin may decrease the cardiotoxic activities of Eflornithine.Experimental
TrastuzumabTrastuzumab may increase the cardiotoxic activities of Eflornithine.Approved, Investigational
Food Interactions
Not Available

References

Synthesis Reference

https://www.google.com/patents/US4330559

General References
  1. Namazi MR: Hypothesis: the potential utility of topical eflornithine against cutaneous leishmaniasis. Indian J Dermatol Venereol Leprol. 2008 Mar-Apr;74(2):158-9. [PubMed:18388383]
  2. Priotto G, Pinoges L, Fursa IB, Burke B, Nicolay N, Grillet G, Hewison C, Balasegaram M: Safety and effectiveness of first line eflornithine for Trypanosoma brucei gambiense sleeping sickness in Sudan: cohort study. BMJ. 2008 Mar 29;336(7646):705-8. doi: 10.1136/bmj.39485.592674.BE. Epub 2008 Mar 5. [PubMed:18321960]
  3. Hoffmann R: A 4-month, open-label study evaluating the efficacy of eflornithine 11.5% cream in the treatment of unwanted facial hair in women using TrichoScan. Eur J Dermatol. 2008 Jan-Feb;18(1):65-70. Epub 2007 Dec 18. [PubMed:18086592]
  4. Jobanputra KS, Rajpal AV, Nagpur NG: Eflornithine. Indian J Dermatol Venereol Leprol. 2007 Sep-Oct;73(5):365-6. [PubMed:17921631]
External Links
KEGG Drug
D07883
KEGG Compound
C07997
PubChem Compound
3009
PubChem Substance
310264864
ChemSpider
2902
BindingDB
50028197
ChEBI
41948
ChEMBL
CHEMBL830
Drugs.com
Drugs.com Drug Page
Wikipedia
Eflornithine
ATC Codes
D11AX16 — EflornithineP01CX03 — Eflornithine
AHFS Codes
  • 84:92.00 — Misc. Skin and Mucous Membrane Agents
FDA label
Download (243 KB)
MSDS
Download (48.1 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1Active Not RecruitingTreatmentNeuroblastomas1
1CompletedTreatmentNeuroblastomas1
1RecruitingTreatmentDiabetes, Diabetes Mellitus Type 11
1RecruitingTreatmentNeuroblastomas1
1, 2RecruitingTreatmentNeuroblastoma Recurrent1
2Active Not RecruitingPreventionAdenomatous Polyps1
2Active Not RecruitingPreventionNeuroblastomas2
2CompletedPreventionCervical Cancers / Precancerous Conditions1
2CompletedPreventionEsophageal Cancers1
2CompletedPreventionProstate Cancer1
2CompletedTreatmentNon-Melanomatous Skin Cancer / Precancerous/Nonmalignant Condition1
2CompletedTreatmentProstate Cancer1
2RecruitingPreventionGastric Intestinal Metaplasia / Malignant Neoplasm of Stomach1
2RecruitingPreventionNeuroblastomas1
2TerminatedTreatmentColorectal Cancers / Familial Adenomatous Polyposis (FAP)1
2WithdrawnDiagnosticFocus of Study: Drug Response Biomarkers, Chemoprevention, Neoplasms1
2, 3Active Not RecruitingTreatmentHuman African Trypanosomiasis (HAT) / Trypanosoma brucei gambiense infection1
3Active Not RecruitingTreatmentFamilial Adenomatous Polyposis (FAP)1
3CompletedPreventionNon-Melanomatous Skin Cancer1
3CompletedPreventionPrecancerous Conditions1
3CompletedTreatmentBladder Cancers1
3CompletedTreatmentTrypanosoma brucei gambiense infection1
3RecruitingTreatmentAnaplastic Astrocytoma (AA) / Recurrent Anaplastic Astrocytoma1
3WithdrawnTreatmentFamilial Adenomatous Polyposis (FAP)1
4CompletedTreatmentHirsutism2
4CompletedTreatmentHuman African Trypanosomiasis (HAT)1
Not AvailableRecruitingPreventionNon-Melanoma Skin Cancer (NMSC)1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
CreamTopical13.9 %
CreamTopical139 mg/g
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US5648394No1994-07-152014-07-15Us
CA2158041No2001-04-032013-05-27Canada
US4330559No1977-07-111997-07-11Us

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility50.0 mg/mLALOGPS
logP-2ALOGPS
logP-2.9ChemAxon
logS-0.56ALOGPS
pKa (Strongest Acidic)2.19ChemAxon
pKa (Strongest Basic)10.2ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count3ChemAxon
Polar Surface Area89.34 Å2ChemAxon
Rotatable Bond Count5ChemAxon
Refractivity37.73 m3·mol-1ChemAxon
Polarizability15.8 Å3ChemAxon
Number of Rings0ChemAxon
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
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-001i-0900000000-df91c4b4acdcbe7cee41
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-00xr-0900000000-9a7e6cedd31e8d4feff3
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-00di-0900000000-83896c5cd4b28a1aeb5b
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-00di-4900000000-3d4818a740257594aecb
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-00e9-9300000000-3f52c4f986a5917af0ff

Taxonomy

Description
This compound belongs to the class of organic compounds known as alpha amino acids. These are amino acids in which the amino group is attached to the carbon atom immediately adjacent to the carboxylate group (alpha carbon).
Kingdom
Organic compounds
Super Class
Organic acids and derivatives
Class
Carboxylic acids and derivatives
Sub Class
Amino acids, peptides, and analogues
Direct Parent
Alpha amino acids
Alternative Parents
Halogenated fatty acids / Branched fatty acids / Amino acids / Monocarboxylic acids and derivatives / Carboxylic acids / Organopnictogen compounds / Organofluorides / Organic oxides / Monoalkylamines / Hydrocarbon derivatives
show 2 more
Substituents
Alpha-amino acid / Branched fatty acid / Halogenated fatty acid / Fatty acyl / Fatty acid / Amino acid / Carboxylic acid / Monocarboxylic acid or derivatives / Alkyl fluoride / Primary amine
show 14 more
Molecular Framework
Aliphatic acyclic compounds
External Descriptors
fluoroamino acid (CHEBI:41948)

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Antagonist
Blocker
General Function
Protein homodimerization activity
Specific Function
Key enzyme of polyamine biosynthesis that converts ornithine into putrescine, which is the precursor for the polyamines, spermidine and spermine.
Gene Name
ODC1
Uniprot ID
P11926
Uniprot Name
Ornithine decarboxylase
Molecular Weight
51147.73 Da
References
  1. Poulin R, Lu L, Ackermann B, Bey P, Pegg AE: Mechanism of the irreversible inactivation of mouse ornithine decarboxylase by alpha-difluoromethylornithine. Characterization of sequences at the inhibitor and coenzyme binding sites. J Biol Chem. 1992 Jan 5;267(1):150-8. [PubMed:1730582]

Drug created on March 19, 2008 10:19 / Updated on November 14, 2017 08:11