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

Drug-Target Interaction

Drug

show drug details
PubChem ID:5291
Structure:
Synonyms:
152459-95-5
1iep
1xbb
4-(4-METHYL-PIPERAZIN-1-YLMETHYL)-N-[4-METHYL-3-(4-PYRIDIN-3-YL-PYRIMIDIN-2-YLAMINO)-PHENYL]-BENZAMIDE
4-[(4-methyl-1-piperazinyl)methyl]-N-[4-methyl-3-[[4-(3-pyridinyl)-2-pyrimidinyl]amino]phenyl]-benzamide methanesulfonate
4-[(4-methylpiperazin-1-yl)methyl]-N-[4-methyl-3-[(4-pyridin-3-ylpyrimidin-2-yl)amino]phenyl]benzamide
4-[(4-methylpiperazin-1-yl)methyl]-N-{4-methyl-3-[(4-pyridin-3-ylpyrimidin-2-yl)amino]phenyl}benzamide
alpha-(4-Methyl-1-piperazinyl)-3'-((4-(3-pyridyl)-2-pyrimidinyl)amino)-p-tolu-p-toluidide
alpha-(4-methyl-1-piperazinyl)-3'-((4-(3-pyridyl)-2-pyrimidinyl)amino)-p-toluidide
Benzamide,
Benzamide, 4-((4-methyl)-1-piperazinyl)methyl)-N-(4-methyl-3-((4-(3-pyridinyl)-2-pyrimidinyl)amino)phenyl)-
Benzamide, 4-[(4-methyl-1-piperazinyl)methyl]-N-[4-methyl-3-[[4-(3-pyridinyl)-2-pyrimidinyl]amino]phenyl]- (9CI)
CCRIS 9076
Cgp 57148
CGP 57148B
CHEBI:45783
DB00619
DB03261
Gleevec
Glivec
Imatinib
Imatinib Mesylate
Imatinib Methansulfonate
Imatinib [INN:BAN]
LS-182208
LS-187106
N-(3-(4-(pyridin-3-yl)pyrimidin-2-ylamino)-4-methylphenyl)-4-((4-methylpiperazin-1-yl)methyl)benzamide
NCGC00159456-02
NCGC00159456-03
NCGC00159456-04
nchembio.117-comp23
nchembio.162-comp5
nchembio.83-comp14
STI
STI 571
sti-571
STI571
STK617705
STOCK6S-47743
ATC-Codes:
Side-Effects:
Side-EffectFrequency
nausea0.4300001
musculoskeletal pain0.28000003
diarrhea0.26666668
vomiting0.26166666
fatigue0.258
muscle cramps0.22173686
edema0.19282351
arthralgia0.185
abdominal pain0.17666666
headache0.17099999
neutropenia0.1550244
dyspepsia0.1525
fever0.1481875
thrombocytopenia0.12565787
hemorrhage0.125
asthenia0.1184
weight gain0.11631249
cough0.1045
myalgia0.10366666
dyspnea0.099833325
nasopharyngitis0.098400004
pharyngitis0.0925
rash0.08903123
anemia0.08858535
anorexia0.08
night sweats0.07666666
pneumonia0.07000001
dizziness0.06933333
upper respiratory tract infection0.068799995
sinusitis0.061000004
insomnia0.060499996
hypokalemia0.057999995
constipation0.056599997
chest pain0.052000005
pruritus0.049399998
gastrointestinal hemorrhage0.042333335
influenza0.030666666
anxiety0.029439993
elevated alkaline phosphatase0.017857144
elevated sgot0.017222222
psoriasis0.009999999
sexual dysfunction0.009999999
peripheral neuropathy0.009999999
purpura0.009999999
menorrhagia0.009999999
herpes zoster0.009999999
hypotension0.009999999
nail disorder0.009999999
hypertension0.009999999
breast enlargement0.009999999
pancytopenia0.009999999
herpes simplex0.009999999
hematuria0.009999999
renal failure0.009999999
exfoliative dermatitis0.009999999
dehydration0.009999999
weight decreased0.009999999
hypophosphatemia0.009999999
dry skin0.009999999
migraine0.009999999
ldh increased0.009999999
sepsis0.009999999
peripheral coldness0.009999999
photosensitivity0.009999999
urinary frequency0.009999999
somnolence0.009999999
vertigo0.009999999
gout0.009999999
sciatica0.009999999
gastroenteritis0.009999999
gastritis0.009999999
flushing0.009999999
gastric ulcer0.009999999
syncope0.009999999
dry eye0.009999999
tachycardia0.009999999
tinnitus0.009999999
alopecia0.009999999
cardiac failure0.009181817
paresthesia0.0055
mouth ulceration0.0028000001
abdominal distension0.0028000001
gastroesophageal reflux0.0028000001
hepatitis0.0028000001
stevens - johnson syndrome0.001818182
dts0.0010
convulsions0.0010
diverticulitis0.0010
vitreous hemorrhage0.0010
vascular disorders0.0010
embolism0.0010
eosinophilia0.0010
erythema multiforme0.0010
conjunctivitis0.0010
glaucoma0.0010
retinal hemorrhage0.0010
acute febrile neutrophilic dermatosis0.0010
hepatic failure0.0010
confusion0.0010
aplastic anemia0.0010
osteonecrosis0.0010
shortness of breath0.0010
angioedema0.0010
vision blurred0.0010
ascites0.0010
cancer0.0010
vaginal discharge0.0010
avascular necrosis0.0010
interstitial pneumonitis0.0010
joint swelling0.0010
cardiac tamponade0.0010
colitis0.0010
cardiac disease0.0010
pulmonary fibrosis0.0010
infections0.0010
pericarditis0.0010
jaundice0.0010
leukemia0.0010
sarcoma0.0010
acute lymphoblastic leukemia0.0010
chronic myeloid leukemia0.0010
hyperkalemia0.0010
papilledema0.0010
pancreatitis0.0010
hyponatremia0.0010
tumor0.0010
lymphoma0.0010
hypersensitivity0.0010
mpd0.0010
watery eyes0
nephrosis0
myelodysplastic syndrome0
pain0
dyspnea on exertion0
elevated liver enzymes0
cardiomyopathy0
lymphopenia0
leukopenia0
back pain0
nephropathy0
blistering0
sore throat0
memory impairment0
cerebral hemorrhage0
bone pain0
petechiae0
congestive heart failure0
epistaxis0
pleural effusion0
flatulence0
blood dyscrasia0
shock0
alveolar proteinosis0
rhinitis0
pulmonary edema0
melena0
ecchymosis0
hepatic necrosis0
varicella0
weakness0
lower respiratory infection0
constitutional symptoms0
peripheral edema0
papilloma0
dermatitis0
pericardial effusion0
viral infection0
gynecomastia0

Target

show target details
Uniprot ID:AKT1_MOUSE
Synonyms:
AKT1 kinase
C-AKT
PKB
Protein kinase B
RAC-alpha serine/threonine-protein kinase
RAC-PK-alpha
Thymoma viral proto-oncogene
EC-Numbers:2.7.11.1
Organism:Mouse
Mus musculus
PDB IDs:-

Binding Affinities:

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

References:

10918610
Growth inhibition and modulation of kinase pathways of small cell lung cancer cell lines by the novel tyrosine kinase inhibitor STI 571.. W L Wang; M E Healy; M Sattler; S Verma; J Lin; G Maulik; C D Stiles; J D Griffin; B E Johnson; R Salgia (2000) Oncogene display abstract
Small cell lung cancer (SCLC) is an aggressive cancer characterized by several autocrine growth mechanisms including stem cell factor and its receptor c-Kit. In order to arrive at potentially new and novel therapy for SCLC, we have investigated the effects of the tyrosine kinase inhibitor, STI 571, on SCLC cell lines. It has been previously reported that STI 571 does not only inhibit cellular Abl tyrosine kinase activity but also the PDGF receptor and c-Kit tyrosine kinases at similar concentrations (approximately 0.1 microM). There is no expression of the PDGF-receptor, and the Abl kinase is not activated by SCLC, but over 70% of SCLC contain the c-Kit receptor. Utilizing this preliminary data, we have determined that three (NCI-H69, NCI-H146 and NCI-H209) of five (including NCI-H82 and NCI-H249) SCLC cell lines had detectable c-Kit receptors and were inhibited in growth and viability at concentrations 1 - 5 microM of STI 571 after 48 h of treatment. The SCLC cell lines, NCI-H69, NCI-H146 and NCI-H209, showed a dose-response (tested between 0.1 - 10 microM) inhibition of tyrosine phosphorylation of c-Kit as well as in vitro kinase activity (at 5 microM) of c-Kit in response to STI 571. STI 571 inhibited cell motility, as assessed by time-lapsed video microscopy, within 6 h of STI 571 treatment (5 microM). STI 571 also decreased intracellular levels of reactive oxygen species (ROS) by at least 60%, at a concentration (5 microM) that also inhibited cell growth. Cell cycle analysis of STI 571 responsive cells showed that cells were generally slowed in G2/M phase, but there was no arrest at G1/S. A downstream phosphorylation target of c-Kit, Akt, was not phosphorylated in response to stem cell factor in the presence of STI 571. These data imply that STI 571 inhibits growth of SCLC cells through a mechanism that involves inactivation of the tyrosine kinase c-Kit. The effectiveness of STI 571 in this study suggests this drug may be useful in a clinical trial, for patients with SCLC. Oncogene (2000) 19, 3521 - 3528
15221957
Different inhibitory effect of imatinib on phosphorylation of mitogen-activated protein kinase and Akt and on proliferation in cells expressing different types of mutant platelet-derived growth factor receptor-alpha.. Akiko Ohashi; Kazuo Kinoshita; Koji Isozaki; Toshirou Nishida; Yasuhisa Shinomura; Yukihiko Kitamura; Seiichi Hirota (2004) International journal of cancer. Journal international du cancer display abstract
Most gastrointestinal stromal tumors (GISTs) have gain-of-function mutations of the c-kit gene. Previously, we found 2 types of gain-of-function mutation of the PDGFRA gene, Val561 to Asp and Asp842 to Val, in about half of GISTs without c-kit gene mutations. Although the inhibitory effect of imatinib on various types of activating mutant KIT has been well examined, that on the activating mutant PDGFRA has not been fully investigated. In the present study, we examined the effect of imatinib on autophosphorylation of mutant PDGFRA, phosphorylation of MAPK and of Akt and in vitro cell proliferation using murine Ba/F3 cells stably transfected with one of the 2 murine-type mutated PDGFRA cDNAs. Imatinib almost completely inhibited autophosphorylation of mutant PDGFRA, phosphorylation of MAPK and Akt as well as in vitro cell proliferation at the concentration of 0.01 microM in cells expressing mutant PDGFRA with Val561 to Asp. However, in cells expressing mutant PDGFRA with Asp842 to Val, imatinib almost completely inhibited autophosphorylation of mutant PDGFRA and phosphorylation of MAPK and Akt at 1.0 microM. The concentration contributing to complete inhibition of in vitro cell proliferation was 10 microM. Ba/F3 cells expressing mutant PDGFRA are a good model to investigate the mechanism of cell proliferation or growth inhibition by imatinib in mutant PDGFRA-driven cells.
17999742
Targeting stromal cells for the treatment of platelet-derived growth factor C-induced hepatocellular carcinogenesis.. Jean S Campbell; Melissa M Johnson; Renay L Bauer; Kelly L Hudkins; Debra G Gilbertson; Kimberly J Riehle; Matthew M Yeh; Charles E Alpers; Nelson Fausto (2007) Differentiation; research in biological diversity display abstract
Non-invasive therapies for the treatment of hepatocellular carcinoma (HCC) would be of great benefit to public health. To this end, we have developed a platelet-derived growth factor-C (PDGF-C) transgenic (Tg) mouse model, which mimics many aspects of human liver carcinogenesis. Specifically, overexpression of PDGF-C results in liver fibrosis, which is preceded by activation and proliferation of hepatic stellate cells, and is followed by the development of dysplastic lesions and angiogenesis, and progression to HCCs by 8 months of age. Here, we show that PDGF-C overexpression induces the proliferation of endothelial-like cells that are present in tumors and adjacent non-neoplastic parenchyma. The protein tyrosine kinase inhibitor, imatinib (Gleevec), decreases the proliferation of non-parenchymal cells (NPC) in vitro and in vivo, with concomitant inhibition of Akt. In vivo treatment with imatinib also blocks the expression of CD34 in PDGF-C Tg mice. Decreased NPC proliferation and CD34 expression correlated with lower levels of active ERK1/2 and total levels of PDGF receptor alpha (PDGFRalpha). In summary, the small molecule inhibitor imatinib attenuates stromal cell proliferation in PDGF-C-induced HCC, which coincides with decreased expression of both CD34 and PDGFRalpha, and activated Akt. Our findings suggest that imatinib may be efficacious in the treatment of hepatocarcinogenesis, particularly when neovascularization is present.