Identification
NameEflornithine
Accession NumberDB06243
TypeSmall Molecule
GroupsApproved, Withdrawn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 KeyDetails
Eflornithine hydrochloride4NH22NDW9H 96020-91-6FJPAMFNRCFEGSD-UHFFFAOYSA-NDetails
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
VaniqaCream139 mg/gTopicalAllergan2013-06-01Not applicableUs
VaniqaCream139 mg/gTopicalPhysicians Total Care, Inc.2004-07-26Not applicableUs
VaniqaCream13.9 %TopicalCipher Pharmaceuticals Inc.2005-11-01Not applicableCanada
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International BrandsNot Available
Brand mixturesNot Available
Categories
UNIIZQN1G5V6SR
CAS number70052-12-9
WeightAverage: 182.171
Monoisotopic: 182.08668396
Chemical FormulaC6H12F2N2O2
InChI KeyVLCYCQAOQCDTCN-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
PharmacodynamicsNot 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.

TargetKindPharmacological actionActionsOrganismUniProt ID
Ornithine decarboxylaseProteinyes
antagonist
blocker
HumanP11926 details
Related Articles
AbsorptionNot Available
Volume of distributionNot Available
Protein bindingNot Available
Metabolism

Not metabolized

Route of elimination

Renal

Half life

8 hours

ClearanceNot Available
ToxicityNot Available
Affected organisms
  • Humans and other mammals
  • Yeast, Molds, Trypanosomes
  • Trypanosoma brucei gambiense
PathwaysNot Available
Pharmacogenomic Effects/ADRs Not Available
Interactions
Drug Interactions
DrugInteractionDrug group
AcetyldigitoxinAcetyldigitoxin may decrease the cardiotoxic activities of Eflornithine.Approved
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
DeslanosideDeslanoside may decrease the cardiotoxic activities of Eflornithine.Approved
DigitoxinDigitoxin may decrease the cardiotoxic activities of Eflornithine.Approved
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
OleandrinAnvirzel may decrease the cardiotoxic activities of Eflornithine.Experimental
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
TrastuzumabTrastuzumab may increase the cardiotoxic activities of Eflornithine.Approved, Investigational
Food InteractionsNot 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
ATC CodesD11AX16 — EflornithineP01CX03 — Eflornithine
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelDownload (243 KB)
MSDSDownload (48.1 KB)
Clinical Trials
Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedTreatmentNeuroblastomas1
1RecruitingTreatmentDiabetes, Diabetes Mellitus Type 11
1RecruitingTreatmentNeuroblastomas2
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
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage forms
FormRouteStrength
CreamTopical13.9 %
CreamTopical139 mg/g
PricesNot Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US5648394 No1994-07-152014-07-15Us
CA2158041 No2001-04-032013-05-27Canada
US4330559 No1977-07-111997-07-11Us
Properties
StateSolid
Experimental PropertiesNot 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 featuresNot Available
Spectra
Mass Spec (NIST)Not Available
Spectra
Spectrum TypeDescriptionSplash Key
Predicted GC-MSPredicted GC-MS Spectrum - GC-MSNot Available
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ , positivesplash10-001i-0900000000-df91c4b4acdcbe7cee41View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ , positivesplash10-00xr-0900000000-9a7e6cedd31e8d4feff3View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ , positivesplash10-00di-0900000000-83896c5cd4b28a1aeb5bView in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ , positivesplash10-00di-4900000000-3d4818a740257594aecbView in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ , positivesplash10-00e9-9300000000-3f52c4f986a5917af0ffView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, NegativeNot Available
Taxonomy
DescriptionThis 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).
KingdomOrganic compounds
Super ClassOrganic acids and derivatives
ClassCarboxylic acids and derivatives
Sub ClassAmino acids, peptides, and analogues
Direct ParentAlpha amino acids
Alternative ParentsHalogenated fatty acids / Branched fatty acids / Amino acids / Monocarboxylic acids and derivatives / Carboxylic acids / Organopnictogen compounds / Organofluorides / Organic oxides / Monoalkylamines / Hydrocarbon derivatives
SubstituentsAlpha-amino acid / Branched fatty acid / Halogenated fatty acid / Fatty acyl / Fatty acid / Amino acid / Carboxylic acid / Monocarboxylic acid or derivatives / Alkyl fluoride / Primary amine
Molecular FrameworkAliphatic acyclic compounds
External Descriptorsfluoroamino acid (CHEBI:41948 )

Targets

Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
antagonistblocker
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 September 01, 2017 11:27