Home
Drugs
Targets
Pathways
Ontologies
Cyp450s
Adv.search
Help/FAQ

Drug-Target Interaction

Drug

show drug details
PubChem ID:68740
Structure:
Synonyms:
(1-hydroxy-2-(1H-imidazol-1-yl)ethylidene)bisphosphonic acid
(1-hydroxy-2-imidazol-1-yl-1-phosphonoethyl)phosphonic acid
(1-hydroxy-2-imidazol-1-yl-phosphonoethyl)phosphonic acid monohydrate
(1-Hydroxy-2-imidazol-1-ylethylidene)diphosphonic acid
118072-93-8
2-(imidazol-1-yl)-1-hydroxyethane-1,1-diphosphonic acid
2-(imidazol-1-yl)-1-hydroxyethylidene-1,1-bisphosphonic acid
AC-1092
AC1L2ACJ
AC1Q6RN3
Aclasta
AKOS005145739
BIDD:GT0292
BIDD:PXR0134
Bio-0112
Bisphosphonate 3
C088658
CGP 42'446
CGP 42446
CGP 42446A
CGP-42'446
CGP-42446
CHEBI:46557
CHEMBL924
D08689
DB00399
FT-0082657
HMS2089O09
I06-0710
KS-1132
LS-181815
NCGC00159521-02
NCGC00159521-03
Novartis brand of zoledronic acid
NSC721517
Phosphonic acid, (1-hydroxy-2-(1H-imidazol-1-yl)ethylidene)bis-
Phosphonic acid,[1-hydroxy-2-(1H-imidazol-1-yl)ethylidene]bis-
Reclast
Reclast (TN)
S00092
S1314_Selleck
STOCK1N-71622
UNII-70HZ18PH24
ZOL
Zoledronate
Zoledronic acid
Zoledronic acid (INN)
Zoledronic acid [USAN:INN]
Zoledronic Acid-Supplied by Selleck Chemicals
Zometa
Zometa (Novartis)
Zometa (TN)
Zometa Concentrate
Zometa, Zomera, Aclasta and Reclast, Zoledronic Acid
[1-hydroxy-2-(1H-imidazol-1-yl)ethane-1,1-diyl]bis(phosphonic acid)
ATC-Codes:
Side-Effects:
Side-EffectFrequency
constipation0.21333335
nausea0.19399999
dyspnea0.18
cough0.17
insomnia0.155
arthralgia0.14359999
bone pain0.14183335
hypophosphatemia0.13952382
diarrhea0.13049999
agitation0.13
hyperthermia0.12711112
anxiety0.125
hypokalemia0.12
neutropenia0.12
moniliasis0.12
alopecia0.12
headache0.11575
vomiting0.112
dermatitis0.11
abdominal pain0.10666668
thrombocytopenia0.1
confusion0.099999994
dizziness0.09150001
fatigue0.09116667
paresthesia0.085
weakness0.08066667
stomatitis0.08
vertigo0.078666665
pain in extremity0.07825
myalgia0.078
osteoarthritis0.074
anemia0.07244444
edema0.07066666
influenza0.069
urinary tract infection0.0655
hypertension0.06533334
back pain0.063666664
anorexia0.057
hypotension0.0555
dyspepsia0.0525
peripheral edema0.043666665
weight decreased0.04075
asthenia0.035
shoulder pain0.0345
chills0.0345
upper respiratory tract infection0.033999998
malignant neoplasm0.033545457
pain0.03266667
rash0.03
dehydration0.029000001
neck pain0.029
sore throat0.027333334
atrial fibrillation0.026
muscle spasms0.026
abdominal pain upper0.021666666
hypomagnesemia0.020000001
abdominal distension0.02
chest pain0.0185
malaise0.0155
hypermagnesemia0.012
musculoskeletal pain0.011999999
hypocalcemia0.011666666
allergic reaction0.0010
hyperesthesia0.0010
hypercalcemia0.0010
hematuria0.0010
episcleritis0.0010
coagulopathies0.0010
angioedema0.0010
blurred vision0.0010
bradycardia0.0010
osteonecrosis0.0010
breast cancer0.0010
increased sweating0.0010
anaphylactic reaction0.0010
syncope0.0010
hyperkalemia0.0010
hypernatremia0.0010
shock0.0010
scleritis0.0010
renal failure0.0010
proteinuria0.0010
tremor0.0010
neoplasms0.0010
uveitis0.0010
muscle cramps0.0010
multiple myeloma0.0010
weight increase0.0010
infection0.0010
dry mouth0.0010
hypersensitivity0.0010
liver function tests abnormal0
swelling0
epigastric pain0
heart disease0
mediastinal disorders0
agranulocytosis0
asthma0
pancytopenia0
dysphagia0
cataract0
somnolence0
avascular necrosis0
periodontal disease0
kidney carcinoma0
hallucinations0
lymphoma0
acute renal failure0
chronic renal failure0
pruritus0
urticaria0
cachexia0
conjunctivitis0
pleural effusion0
flushing0
leukopenia0
gingivitis0
malnutrition0
nasopharyngitis0
osteomyelitis0
iritis0
mouth ulceration0
vascular disorders0
azotemia0

Target

show target details
Uniprot ID:ICE_DROME
Synonyms:
Caspase
drICE
EC-Numbers:3.4.22.-
Organism:Drosophila melanogaster
Fruit fly
PDB IDs:-

Binding Affinities:

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

References:

15286715
The farnesyl transferase inhibitor R115777 (Zarnestra) synergistically enhances growth inhibition and apoptosis induced on epidermoid cancer cells by Zoledronic acid (Zometa) and Pamidronate.. Michele Caraglia; Anna Maria D'Alessandro; Monica Marra; Gaia Giuberti; Giovanni Vitale; Caterina Viscomi; Annamaria Colao; Salvatore Del Prete; Pierosandro Tagliaferri; Pierfrancesco Tassone; Alfredo Budillon; Salvatore Venuta; Alberto Abbruzzese (2004) Oncogene display abstract
Pamidronate (PAM) and zoledronic acid (ZOL) are aminobisphosphonates (BPs) able to affect the isoprenylation of intracellular small G proteins. We have investigated the antitumor activity of BPs and R115777 farnesyl transferase inhibitor (FTI) against epidermoid cancer cells. In human epidermoid head and neck KB and lung H1355 cancer cells, 48 h exposure to PAM and ZOL induced growth inhibition (IC(50) 25 and 10 microM, respectively) and apoptosis and abolished the proliferative and antiapoptotic stimuli induced by epidermal growth factor (EGF). In these experimental conditions, ZOL induced apoptosis through the activation of caspase 3 and a clear fragmentation of PARP was also demonstrated. A strong decrease of basal ras activity and an antagonism on its stimulation by EGF was recorded in the tumor cells exposed to BPs. These effects were paralleled by impaired activation of the survival enzymes extracellular signal regulated kinase 1 and 2 (Erk-1/2) and Akt that were not restored by EGF. Conversely, farnesol induced a recovery of ras activity and antagonized the proapoptotic effects induced by BPs. The combined treatment with BPs and R115777 resulted in a strong synergism both in growth inhibition and apoptosis in KB and H1355 cells. The synergistic activity between the drugs allowed BPs to produce tumor cell growth inhibition and apoptosis at in vivo achievable concentrations (0.1 micromolar for both drugs). Moreover, the combination was highly effective in the inhibition of ras, Erk and Akt activity, while farnesol again antagonized these effects. In conclusion, the combination of BPs and FTI leads to enhanced antitumor activity at clinically achievable drug concentrations that resides in the inhibition of farnesylation-dependent survival pathways and warrants further studies for clinical translation.