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Drug-Target Interaction

Drug

show drug details
PubChem ID:387447
Structure:
Synonyms:
179324-69-7
AIDS-004352
AIDS004352
BO2
Boronic acid, [(1(R)-3-methyl-1-[[(2S)-1-oxo-3-phenyl-2-[(pyrazinylcarbonyl)amino]propyl]amino]butyl]-
Boronic acid, [1-[[1-oxo-3-phenyl-2-[(2-pyrazinylcarbonyl) amino]propyl]amino]-3-methylbutyl]-, L-(S)-
Bortezomib
Bortezomib (JAN/USAN/INN)
D03150
DPBA
LDP-341
LPD 341
LPD-341
MLN-341
N-[(1R)-1-(dihydroxyboranyl)-3-methylbutyl]-Nalpha-(pyrazin-2-ylcarbonyl)-L-phenylalaninamide
N-[(1R)-1-(DIHYDROXYBORYL)-3-METHYLBUTYL]-N-(PYRAZIN-2-YLCARBONYL)-L-PHENY
N-[(1R)-1-(DIHYDROXYBORYL)-3-METHYLBUTYL]-N-(PYRAZIN-2-YLCARBONYL)-L-PHENYLALANINAMIDE
NCI60_029010
NSC-681239
NSC681239
PROSCRIPT BORONIC ACID
PS 341
PS-341
Pyz-Phe-boroLeu
Velcade
Velcade (TN)
ATC-Codes:
Side-Effects:
Side-EffectFrequency
diarrhea0.25777435
thrombocytopenia0.23198372
nausea0.22046134
peripheral neuropathy0.1804772
vomiting0.17805077
constipation0.14876074
anemia0.14872852
pyrexia0.12964725
neutropenia0.1256191
anorexia0.121853106
headache0.10995067
arthralgia0.0948449
insomnia0.0939306
cough0.09226433
pain in limb0.09156194
paresthesia0.09006605
dysesthesia0.090066046
upper respiratory tract infection0.0899125
dehydration0.0833335
dyspnea0.074871294
dizziness0.07291497
anxiety0.0701755
nasopharyngitis0.067976
rash0.06785051
muscle cramps0.06596617
dyspepsia0.0657895
bone pain0.058520827
back pain0.057784658
pruritus0.0570175
myalgia0.055298325
edema0.053735647
abdominal pain0.05294372
hypotension0.05116957
vertigo0.048943315
herpes zoster0.04676061
vision blurred0.036883
pneumonitis0.0283652
infection0.020918757
mediastinal disorders0.0010
paraplegia0.0010
acute psychosis0.0010
pericardial effusion0.0010
pericarditis0.0010
gastritis hemorrhagic0.0010
sepsis0.0010
hypoxia0.0010
petechiae0.0010
phlebitis0.0010
pleural effusion0.0010
aspiration pneumonia0.0010
postherpetic neuralgia0.0010
lung infiltration0.0010
ileus paralytic0.0010
pancreatitis0.0010
melena0.0010
meningoencephalitis0.0010
multiple myeloma0.0010
hearing impaired0.0010
myocardial infarction0.0010
respiratory failure0.0010
hyperuricemia0.0010
tumour0.0010
nephrotic syndrome0.0010
neuralgia0.0010
peritonitis0.0010
palsy0.0010
pain0.0010
bradycardia0.0010
psychotic disorder0.0010
pulmonary embolism0.0010
portal vein thrombosis0.0010
urinary incontinence0.0010
urinary tract infection0.0010
urticaria0.0010
vascular disorders0.0010
myocardial ischemia0.0010
atrioventricular block complete0.0010
leukocytoclastic vasculitis0.0010
ventricular tachycardia0.0010
deep venous thrombosis0.0010
virus infection0.0010
agitation0.0010
liver failure0.0010
encephalopathy0.0010
ischemic colitis0.0010
erythema0.0010
toxoplasmosis0.0010
renal failure0.0010
acute respiratory distress syndrome0.0010
seizures0.0010
shock0.0010
septic shock0.0010
sinusitis0.0010
small intestinal obstruction0.0010
spasm0.0010
stomatitis0.0010
stroke0.0010
subarachnoid hemorrhage0.0010
tachycardia0.0010
dyspnea exertional0.0010
sinus arrest0.0010
urinary retention0.0010
lymphopenia0.0010
pancreatitis acute0.0010
confusion0.0010
cystitis0.0010
deafness0.0010
dysphagia0.0010
diplopia0.0010
drug hypersensitivity0.0010
duodenitis0.0010
dysarthria0.0010
embolism0.0010
toxic epidermal necrolysis0.0010
grand mal convulsion0.0010
epistaxis0.0010
fecal impaction0.0010
gastroenteritis0.0010
gastroesophageal reflux0.0010
bilateral hearing loss0.0010
cardiac disorders0.0010
coma0.0010
acute pulmonary edema0.0010
amyloidosis0.0010
anaphylactic reaction0.0010
angina pectoris0.0010
angioedema0.0010
ascites0.0010
aspergillosis0.0010
ataxia0.0010
atelectasis0.0010
atrial fibrillation0.0010
atrial flutter0.0010
bacteremia0.0010
malignancies0.0010
oral candidiasis0.0010
cardiac tamponade0.0010
renal tubular acidosis0.0010
cerebral hemorrhage0.0010
transient ischemic attack0.0010
heart failure0.0010
pulmonary hypertension0.0010
herpes0.0010
calculus renal0.0010
hypokalemia0.0010
herpes simplex0.0010
ophthalmic herpes simplex0.0010
hydronephrosis0.0010
hyperbilirubinemia0.0010
hypocalcemia0.0010
hyperkalemia0.0010
hypernatremia0.0010
inappropriate adh secretion0.0010
hyponatremia0.0010
hypersensitivity0.0010
intestinal perforation0.0010
acute renal failure0.0010
bleeding0.0010
hepatitis0.0010
hematemesis0.0010
subdural hematoma0.0010
chronic obstructive airways disease0.0010
pulmonary disease0.0010
hematuria0.0010
leukopenia0.0010
hemoptysis0.0010
lightheadedness0
chest wall pain0
ischemia0
sterility0
autonomic neuropathy0
polyarthritis0
joint stiffness0
asthenia0
malaise0
postural hypotension0
arrhythmia0
abdominal pain upper0
leukemia0
infertility0
neuropathy0
musculoskeletal pain0
meningitis0
numbness0
hypercalcemia0
skin irritation0
hyperglycemia0
congestive heart failure0
ureteral obstruction0
failure to thrive0
fatigue0
flushing0
syncope0
swelling0
gastritis0
pulmonary edema0
gastrointestinal hemorrhage0
enteritis0
vasculitis0
venous thrombosis0
hypertension0
hypomagnesemia0
weakness0
connective tissue disorders0
hypophosphatemia0
hypochloremia0
peripheral edema0
constitutional symptoms0
burning sensation0
acute febrile neutrophilic dermatosis0
weight loss0
cardiac arrest0

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:

15217830
Targeting mitochondria to overcome conventional and bortezomib/proteasome inhibitor PS-341 resistance in multiple myeloma (MM) cells.. Dharminder Chauhan; Guilan Li; Klaus Podar; Teru Hideshima; Constantine Mitsiades; Robert Schlossman; Nikhil Munshi; Paul Richardson; Finbarr E Cotter; Kenneth C Anderson (2004) Blood display abstract
Bortezomib (PS-341), a selective inhibitor of proteasomes, induces apoptosis in multiple myeloma (MM) cells; however, prolonged drug exposure may result in cumulative toxicity and the development of chemoresistance. Here we show that combining PK-11195 (PK), an antagonist to mitochondrial peripheral benzodiazepine receptors (PBRs), with bortezomib triggers synergistic anti-MM activity even in doxorubicin-, melphalan-, thalidomide-, dexamethasone-, and bortezomib-resistant MM cells. No significant cytotoxicity was noted in normal lymphocytes. Low-dose combined PK and bortezomib treatment overcomes the growth, survival, and drug resistance conferred by interleukin-6 or insulin growth factor within the MM bone marrow milieu. The mechanism of PK + bortezomib-induced apoptosis includes: loss of mitochondrial membrane potential; superoxide generation; release of mitochondrial proteins cytochrome-c (cyto-c) and Smac; and activation of caspases-8/-9/-3. Furthermore, PK + bortezomib activates c-Jun NH2 terminal kinase (JNK), which translocates to mitochondria, thereby facilitating release of cyto-c and Smac from mitochondria to cytosol. Blocking JNK, by either dominant-negative mutant (DN-JNK) or cotreatment with a specific JNK inhibitor SP600125, abrogates both PK + bortezomib-induced release of cyto-c/Smac and induction of apoptosis. Together, these preclinical studies suggest that combining bortezomib with PK may enhance its clinical efficacy, reduce attendant toxicity, and overcome conventional and bortezomib resistance in patients with relapsed refractory MM.
17134969
Bortezomib induces different apoptotic rates in B-CLL cells according to IgVH and BCL-6 mutations.. Eloisa Jantus-Lewintre; Elena Sarsotti; María José Terol; Isabel Benet; Javier García-Conde (2006) Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico display abstract
BACKGROUND: B-cell chronic lymphocytic leukemia (B-CLL) is a remarkably heterogeneous disorder. Some patients have an indolent disease whereas others undergo a more agressive presentation needing treatment. New therapeutics approaches are necessary for the treatment of B-CLL. Bortezomib (Btz), is a proteasome inhibitor, currently undergoing clinical trials whose function, at least in part, by stabilizing the IkappaBalpha protein and inhibiting NFkappaB activation. OBJECTIVE: The objective of this work was to study the effects of Btz on isolated human B-CLL cells, in vitro, and to correlate the differential rates of apoptosis induction with biological variables. MATERIAL AND METHODS: 31 B-CLL samples, from patients in stage A of Binet were used for this study, and the apoptotic effect of Btz on these cells was measured. RESULTS: Our data show that Btz treatment of B-CLL cells induces apoptosis in a time and dose-dependent manner. The apoptosis induction is mediated in part by inhibition of NFkappaB and is dependent on caspases activation. Interesting, in IgVH mutated cells, Btz have statistically significant differences in their in vitro activity on B-CLL cells according to their BCL-6 mutational status. CONCLUSIONS: Btz is a promising pharmacologic agent for the treatment of B-CLL, but its efficacy seems to be related to IgVH and BCL-6 mutational status, therefore, it could be interesting to further investigate the mechanisms involved in the different behavior of the cells in response to apoptosis induction by this drug.