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Drug-Target Interaction

Drug

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PubChem ID:3009
Structure:
Synonyms:
.alpha.-DFMO HCl
2,5-diamino-2-(difluoromethyl)pentanoic acid
2-(Difluoromethyl)-DL-ornithine
2-(Difluoromethyl)ornithine
67037-37-0
67037-37-0 (FREE BASE)
68278-23-9
70052-12-9
96020-91-6
96020-91-6 (HYDROCHLORIDE)
96020-91-6 (mono-hydrochloride, monohydrate)
AC1L1EYW
AIDS-002149
AIDS002149
alpha,delta-Diamino-alpha-(difluoromethyl)valeric acid
alpha-(Difluoromethyl)-DL-ornithine
alpha-Difluoromethylornithine
BRN 2250529
C07997
CCG-204521
CCRIS 3295
CCRIS 3718
CHEBI:41948
CHEMBL830
D,L-alpha-Difluoromethylornithine
D07883
DB03856
DFMO
DFMO (growth regulator)
DFMO HCl
Difluoromethylornithine
Difluromethylornithine
DL-.alpha.-Difluoromethylornithine
DL-alpha-(Difluoromethyl)ornithine
DL-alpha-Difluoromethylornithine
DL-alpha-Difluoromethylornithine hydrochloride
DL-Ornithine, 2-(difluoromethyl)-
DL-Ornithine, 2-(difluoromethyl)-, monohydrochloride
Eflornithine
Eflornithine (INN)
Eflornithine hydrochloride
Eflornithine [INN:BAN]
Eflornithinum
Eflornithinum [Latin]
Eflornitina
Eflornitina [Spanish]
HSCI1_000267
Lopac0_000429
LS-185084
LS-7332
MDL 71,782 A
MDL 71782
MolPort-006-169-327
N-Difluoromethylornithine
NCGC00015316-02
NCGC00015316-03
NCGC00162152-01
NSC337250
Ornidyl
Ornithine, 2-(difluoromethyl)-
pentane-1,4-diamine
RMI 71782
UNII-ZQN1G5V6SR
Vaniqa
ATC-Codes:
Side-Effects:
Side-EffectFrequency
alopecia0
nausea0
numbness0
pruritus0
rosacea0
swelling0
erythema0
vertigo0
dry skin0
herpes simplex0
hemorrhage0
headache0
anorexia0
asthenia0
contact dermatitis0
dizziness0
dyspepsia0
edema0
rash0
folliculitis0
skin irritation0

Target

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Uniprot ID:A5GZ72_HUMAN
Synonyms:
Matrix metalloproteinase 7
EC-Numbers:-
Organism:Homo sapiens
Human
PDB IDs:-

Binding Affinities:

Ki: Kd:Ic 50:Ec50/Ic50:
----

References:

16170669
Inhibitors of polyamine biosynthesis decrease the expression of the metalloproteases meprin alpha and MMP-7 in hormone-independent human breast cancer cells.. Gail L Matters; Andrea Manni; Judith S Bond (2005) Clinical & experimental metastasis display abstract
Inhibition of ornithine decarboxylase (ODC), a key enzyme in polyamine biosynthesis, by the irreversible inhibitor alpha-difluoromethylornithine (DFMO) has been shown to decrease the invasiveness of metastatic human breast cancer cell lines. However, the mechanism by which DFMO acts to reduce invasiveness is unclear. Using the human breast cancer cell line MDA-MB-435, the effect of DFMO on metalloprotease gene expression was investigated. DFMO treatment decreases the expression of the metalloprotease meprin alpha, while concurrent treatment with DFMO and the polyamine putrescine partially restored meprin alpha expression levels. Expression of MMP-7 mRNA was reduced by DFMO, while MMPs-1, -2, -3, -14, and meprin beta were unaffected. Treatment of cells with a second inhibitor of polyamine biosynthesis, the S-adenosylmethionine decarboxylase (SAMDC) inhibitor SAM486A, also resulted in a dosage dependent decrease in meprin alpha and MMP-7 mRNA. In addition, DFMO treatment decreased meprin alpha at the protein level by 2 days of treatment, and MMP-7 protein levels at 4 and 6 days. Previous studies have shown that DFMO treatment increases ERK phosphorylation and signaling through the MAP kinase pathway. The decrease in meprin alpha expression was reversed with the MEK inhibitor PD98059, demonstrating that MAP kinase signaling mediates the effect of DFMO and SAM486A. MDA-MB-435 cells treated with the meprin alpha inhibitor actinonin (5 nM) were less invasive in vitro, indicating that meprin alpha is mechanistically involved in invasion. The decrease in meprin alpha expression in DFMO and SAM486A-treated cells indicates a means by which these compounds can decrease the invasiveness of metastatic breast cancer cells.