EFLORNITHINE HYDROCHLORIDE

Details

Stereochemistry	RACEMIC
Molecular Formula	C6H12F2N2O2.ClH.H2O
Molecular Weight	236.645
Optical Activity	( + / - )
Defined Stereocenters	0 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

O.Cl.NCCCC(N)(C(F)F)C(O)=O

InChI

InChIKey=FJPAMFNRCFEGSD-UHFFFAOYSA-N

InChI=1S/C6H12F2N2O2.ClH.H2O/c7-4(8)6(10,5(11)12)2-1-3-9;;/h4H,1-3,9-10H2,(H,11,12);1H;1H2

HIDE SMILES / InChI

Molecular Formula	H2O
Molecular Weight	18.0153
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Molecular Formula	C6H12F2N2O2
Molecular Weight	182.1685
Charge	0
Count

Stereochemistry	RACEMIC
Additional Stereochemistry	No
Defined Stereocenters	0 / 1
E/Z Centers	0
Optical Activity	( + / - )

Molecular Formula	ClH
Molecular Weight	36.461
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Description
Sources: http://www.drugbank.ca/drugs/DB06243
Curator's Comment: Description was created based on several sources, including http://www.accessdata.fda.gov/drugsatfda_docs/label/2000/21145lbl.pdf

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. 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.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Ornithine decarboxylase 15 Target ID: CHEMBL1869 Sources: http://www.drugbank.ca/drugs/DB06243	Inhibitor 8297
Trypanosoma brucei 3 Target ID: CHEMBL612849 Sources: https://www.ncbi.nlm.nih.gov/pubmed/23031595	Inhibitor 8297		8.3 µM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Facial hirsutism 3 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2000/21145lbl.pdf	Primary		Approved 8429	VANIQA Approved Use Reduction of unwanted facial hair in women. Launch Date 2000

C_max

Value	Dose	Co-administered	Analyte	Population
484 μM EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/15141331	100 mg/kg 4 times / day steady-state, oral dose: 100 mg/kg route of administration: Oral experiment type: STEADY-STATE co-administered:		EFLORNITHINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
4430 μM × h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/15141331	100 mg/kg 4 times / day steady-state, oral dose: 100 mg/kg route of administration: Oral experiment type: STEADY-STATE co-administered:		EFLORNITHINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
10.6 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/15141331	100 mg/kg 4 times / day steady-state, oral dose: 100 mg/kg route of administration: Oral experiment type: STEADY-STATE co-administered:		EFLORNITHINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

Doses

Dose	Population	Adverse events
1 g/m2 1 times / day multiple, oral Highest studied dose Dose: 1 g/m2, 1 times / day Route: oral Route: multiple Dose: 1 g/m2, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/9516915/	unhealthy, 23-41 n = 6 Health Status: unhealthy Condition: cervical intraepithelial neoplasia Age Group: 23-41 Sex: F Population Size: 6 Sources: https://pubmed.ncbi.nlm.nih.gov/9516915/	Other AEs: Diarrhea, Dizziness... Other AEs: Diarrhea (grade 1, 2 patients) Dizziness (grade 1-2, 1 patient) Malaise (grade 1-2, 1 patient) Mood change (grade 1, 1 patient) Myalgia (grade 1, 1 patient) Nausea (grade 1, 3 patients) Nosebleed (grade 1, 2 patients) Pruritus (grade 1, 1 patient) Skin rash (grade 1-2, 1 patient) Stomatitis (grade 1, 3 patients) Sources: https://pubmed.ncbi.nlm.nih.gov/9516915/
13.9 % 2 times / day multiple, topical Recommended Dose: 13.9 %, 2 times / day Route: topical Route: multiple Dose: 13.9 %, 2 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2000/21145lbl.pdf	unhealthy, adult n = 1373 Health Status: unhealthy Condition: hirsutism Age Group: adult Sex: F Population Size: 1373 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2000/21145lbl.pdf	Other AEs: Acne, Pseudofolliculitis barbae... Other AEs: Acne (10.8%) Pseudofolliculitis barbae (4.9%) Stinging skin (4.1%) Headache (4%) Burning skin (3.5%) Dry skin (3.3%) Pruritus (3.1%) Erythema (2.5%) Tingling skin (2.2%) Dyspepsia (1.9%) Skin irritation (1.8%) Rash (1.5%) Alopecia (1.3%) Dizziness (1.3%) Folliculitis (1%) Ingrown hair (0.9%) Edema face (0.7%) Anorexia (0.7%) Nausea (0.7%) Asthenia (0.3%) Vertigo (0.1%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2000/21145lbl.pdf

AEs

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:41948	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:41948
MolPort	MolPort-006-169-327	https://www.molport.com/shop/molecule-link/MolPort-006-169-327
eMolecules	32452415	https://www.emolecules.com/cgi-bin/more?vid=32452415

PubMed

Title	Date	PubMed
Characterization of spermine uptake by Ehrlich tumour cells in culture.	2001	11764408
Topical eflornithine.	2001	11705097
The effect of polyamine biosynthesis inhibition on growth and differentiation of the phytopathogenic fungus Sclerotinia sclerotiorum.	2001 Dec	11827210
The future of colon cancer prevention.	2001 Dec	11795446
Beyond tamoxifen new endpoints for breast cancer chemoprevention, new drugs for breast cancer prevention.	2001 Dec	11795443
Chemopreventive agents inhibit aberrant proliferation of the aneuploid phenotype in a colon epithelial cell line established from Apc 1638N [+/-] mouse.	2001 Dec	11795437
Eflornithine.	2001 Dec 1	11763800
Differential regulation of nitric oxide synthase-2 and arginase-1 by type 1/type 2 cytokines in vivo: granulomatous pathology is shaped by the pattern of L-arginine metabolism.	2001 Dec 1	11714822
The effect of DFMO induced uptake of [3H] putrescine on human glioma cells.	2001 Nov	11817704
[Current treatment of hypertrichosis].	2001 Nov	11757465
Cell culture analysis of the regulatory frameshift event required for the expression of mammalian antizymes.	2001 Nov	11733031
Availability and affordability of treatment for Human African Trypanosomiasis.	2001 Nov	11703853
Spermidine is essential for normal proliferation of trypanosomatid protozoa.	2001 Nov 23	11728444
No alterations in the performance of two interval timing operant tasks after alpha-difluoromethylornithine (DFMO)-induced cerebellar stunting.	2001 Nov 29	11704259
Cytoskeletal organization and cell motility correlates with metastatic potential and state of differentiation in prostate cancer.	2001 Sep	11785653
Winterbottom's sign and hypertrophic cardiomyopathy.	2002	12195887
Influence of polyamines on in vitro and in vivo features of aggressive and metastatic behavior by human breast cancer cells.	2002	11964084
Chemotherapy of human African trypanosomiasis.	2002	11860365
Plating densities, alpha-difluoromethylornithine effects and time dependence on the proliferation of IEC-6 cells.	2002 Apr	12133287
Polyamine-dependent migration of retinal pigment epithelial cells.	2002 Apr	11923270
Effects of polyamines on the release of gonadotropin-releasing hormone and gonadotropins in developing female rats.	2002 Apr	11910050
Activation of K(+) channels and increased migration of differentiated intestinal epithelial cells after wounding.	2002 Apr	11880277
Quantitation of polyamines in hypothalamus and pituitary of female and male developing rats.	2002 Apr 19	11911991
The preovulatory rise of ovarian ornithine decarboxylase is required for progesterone secretion by the corpus luteum.	2002 Apr 26	12054570
Inhibition of placental ornithine decarboxylase by DL-alpha-difluoro-methyl ornithine causes fetal growth restriction in rat.	2002 Feb 8	11883715
The ornithine decarboxylase inhibitor, difluoromethylornithine, inhibits casein kinase II activity, c-Myc expression and normal human keratinocyte proliferation.	2002 Jan	11876528
Chemoprevention of colorectal cancer.	2002 Jan	11808936
Modulation of biologic endpoints by topical difluoromethylornithine (DFMO), in subjects at high-risk for nonmelanoma skin cancer.	2002 Jan	11801552
African trypanosomiasis in travelers returning to the United Kingdom.	2002 Jan	11749752
Activities of arginase I and II are limiting for endothelial cell proliferation.	2002 Jan	11742824
[Chemoprevention of colorectal cancer].	2002 Jan 26	11859737
Regulation of ornithine decarboxylase in B16 mouse melanoma cells: synergistic activation of melanogenesis by alphaMSH and ornithine decarboxylase inhibition.	2002 Jan 30	11853879
Glucocorticoids and polyamine inhibitors synergize to kill human leukemic CEM cells.	2002 Jan-Feb	11922393
Treatment of human African trypanosomiasis--present situation and needs for research and development.	2002 Jul	12127356
RhoA inactivation inhibits cell migration but does not mediate the effects of polyamine depletion.	2002 Jul	12105848
Polyamines modulate the interaction between nuclear receptors and vitamin D receptor-interacting protein 205.	2002 Jul	12089346
Stress-induced dynamic changes in mouse brain polyamines. Role in behavioral reactivity.	2002 Jul 5	12088835
Are polyamines involved in olfaction? An EAG and biochemical study in Periplaneta americana antennae.	2002 Jun	12052778
Involvement of polyamines in root development at low temperature in the subantarctic cruciferous species Pringlea antiscorbutica.	2002 Jun	12021294
Polyamine depletion prevents camptothecin-induced apoptosis by inhibiting the release of cytochrome c.	2002 Jun	11997243
Polyamine uptake is necessary for a normal biochemical maturation of astrocytes in culture.	2002 Jun 12	12060814
Effects of ornithine 2-oxoglutarate on neutrophils in stressed rats: evidence for the involvement of nitric oxide and polyamines.	2002 Mar	11869169
Suppression of UV carcinogenesis by difluoromethylornithine in nucleotide excision repair-deficient Xpa knockout mice.	2002 Mar 1	11888902
[Hypertrichosis and hirsutism].	2002 May	12090123
Selective exclusion by the polyamine transporter as a mechanism for differential radioprotection of amifostine derivatives.	2002 May	12006551
Effects of difluoromethylornithine on growth inhibition and apoptosis in human cervical epithelial and cancerous cell lines.	2002 May	11972386
Protein kinase Cdelta-mediated signal to ornithine decarboxylase induction is independent of skin tumor suppression.	2002 May 16	12032864
Effect of polyamine depletion on cone photoreceptors of the developing rabbit retina.	2002 Sep	12202533
Altered expression of c-myc, p16 and p27 in rat colon tumors and its reversal by short-term treatment with chemopreventive agents.	2002 Sep	12189186
Polyamines regulate beta-catenin tyrosine phosphorylation via Ca(2+) during intestinal epithelial cell migration.	2002 Sep	12176729

Patents

Sample Use Guides

In Vivo Use Guide

Usual Adult Dose for Hirsutism Apply a thin layer of eflornithine topical cream to affected areas of the face and adjacent involved areas under the chin and rub in thoroughly. Do not wash treated area for at least 4 hours. Use twice a day, allowing at least 8 hours between applications or as directed by a physician. Continue to use hair removal techniques as needed in conjunction with eflornithine. Apply eflornithine at least 5 minutes after hair removal.

Route of Administration: Topical

In Vitro Use Guide

Eflornithine (0.01 - 1 mM) treatment suppressed proliferation of 4T1 murine mammary cancer cells in culture.

Substance Class	Chemical Created by `admin` on `Fri Dec 15 15:25:13 GMT 2023` Edited by `admin` on `Fri Dec 15 15:25:13 GMT 2023`
Record UNII	4NH22NDW9H
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

EFLORNITHINE HYDROCHLORIDE

Official Name

English

EFLORNITHINE HYDROCHLORIDE [ORANGE BOOK]

Common Name

English

EFLORNITHINE HYDROCHLORIDE MONOHYDRATE

Common Name

English

DL-ORNITHINE, 2-(DIFLUOROMETHYL)-, MONOHYDROCHLORIDE, MONOHYDRATE

Common Name

English

MDL 71,782 A

Code

English

Eflornithine hydrochloride [WHO-DD]

Common Name

English

2,5-DIAMINO-2-(DIFLUOROMETHYL)PENTANOIC ACID, MONOHYDROCHLORIDE, MONOHYDRATE

Common Name

English

ORNIDYL

Brand Name

English

RMI-71782-A

Code

English

EFLORNITHINE HYDROCHLORIDE [MART.]

Common Name

English

EFLORNITHINE HYDROCHLORIDE MONOHYDRATE [MI]

Common Name

English

MDL-71782-A

Code

English

VANIQA

Brand Name

English

EFLORNITHINE HYDROCHLORIDE [USP-RS]

Common Name

English

EFLORNITHINE HCL

Common Name

English

2-(DIFLUOROMETHYL)-DL-ORNITHINE MONOHYDROCHLORIDE, MONOHYDRATE

Systematic Name

English

EFLORNITHINE HYDROCHLORIDE [USAN]

Common Name

English

EFLORNITHINE HYDROCHLORIDE [VANDF]

Common Name

English

Classification Tree Code System Code

EU-Orphan Drug

EU/3/02/087