印度伊马替尼

产品描述

matinib is an inhibitor of the receptor tyrosine kinases c-Abl, Bcr-Abl, PDGFR, and c-Kit (IC50: 600/100/100 nM).

靶点活性

c-Kit,100 nM (cell free)

PDGFR,100 nM (cell free)

v-Abl,600nM

体外活性

Imatinib (STI 571) inhibited c-kit autophosphorylation, activation of mitogen-activated protein (MAP) kinase, and activation of Akt without altering total protein levels of c-kit, MAP kinase, or Akt. The concentration that produced 50% inhibition for these effects was approximately 100 nmol/L. STI 571 also significantly decreased SLF-dependent growth of M-07e cells in a dose-dependent manner and blocked the antiapoptotic activity of SLF [1]. Imatinib mesylate had a more similar effect on Bcr/Abl- and c-Kit–dependent proliferation, with an IC50 of 19 nM in R10(-) cells and 82 nM in MO7e cells growing in the presence of SCF (KL, Kit ligand), respectively [2]. STI571 inhibited tyrosine phosphorylation and cell growth of Ba/F3 cells expressing BCR/ABL, TEL/ABL, TEL/PDGFbetaR, and TEL/ARG with an IC(50) of approximately 0.5 microM in each case, but it had no effect on untransformed Ba/F3 cells growing in IL-3 or on Ba/F3 cells transformed by TEL/JAK2 [3].

体内活性

Imatinib (25 mg/kg/day, p.o.) significantly reduced the endometriosis score compared to normal saline. It significantly decreased the ovarian follicle number compared to normal saline. The CD117 staining score of rats administered imatinib was significantly lower than that of the rats received normal saline [4]. After intraperitoneal injection of STI571, it has 80%, 40% and 78% growth inhibition of SCLC6, SCLC61, and SCLC108 tumors, respectively, without any significant inhibition of SCLC74 tumor growth [5].

激酶实验

PDGF receptor kinase activity: PDGF receptor is immunoprecipitated from BALB/c 3T3 cell extracts with rabbit antiserum to the murine PDGF receptor for 2 hours on ice. Protein A-Sepharose beads are used to collect the antigen-antibody complexes. The immunoprecipitates are washed twice with TNET (50 mM Tris, pH 7.5, 140 mM NaCl, 5 mM EDTA, 1% Triton X-100), once with TNE (50 mM Tris, pH 7.5, 140 mM EDTA), and once with kinase buffer (20 mM Tris, pH 7.5,10 mM MgCl2). After stimulation with PDGF (50 ng/mL) for 10 minutes at 4 °C, different concentrations of drug are added to the reaction mixture. PDGF receptor kinase activity is determined by incubation with 10 μCi [7-33P]-ATP and l μM ATP for 10 minutes at 4 °C. Immune complexes are separated by SDS-PAGE on 7.5% gels.

细胞实验

M-07e cells were grown in serum-free RPMI 1640 at 37°C for approximately 18 hours before they were incubated for 90 minutes in the presence of various concentrations of STI 571. The cells were then pelleted and resuspended in 1 mL RPMI 1640. STI 571 was added to each tube to achieve the same concentration used during the 90 minutes of preincubation. The cells were then incubated with inhibitor and growth factor (SLF or GM-CSF) for 15 minutes at 37°C. Subsequently, the cell pellets were lysed with 100 to 250 μL of protein lysis buffer (50 mmol/L Tris, 150 mmol/L sodium chloride, 1% NP-40, and 0.25% deoxycholate, with addition of the inhibitors aprotinin, leupeptin, pepstatin, phenylmethyl sulfonyl fluoride, and sodium orthovanadate). Western immunoblot analysis was performed as previously described.41Experiments with HMC-1 cells were performed in the same way except that neither SLF nor GM-CSF was added [1].

细胞系： BON-1 cells and NCI-H727 cells

动物实验

Swiss mice (nu/nu, female), weighing 30 g, 6 – 8 weeks old, were bred in the animal facilities, maintained under specific pathogen-free conditions with artificial lighting (12 hr light/12 hr dark cycle) and fed a regular diet and water ad libitum. For therapeutic trials, the tumor-bearing mice were randomly divided into equivalent groups of 5 to 12 animals and mice were treated as soon as the xenografted tumors reached a diameter of 5 mm (or a tumor volume of approximately 60 mm^3). Four different human tumors were used: the SCLC6, SCLC61, SCLC 74 and SCLC108 small cell lung cancers. STI571 was administered at a total dosage of 70 or 100 mg/kg per day in 1 or 2 intraperitoneal injections, with or without etoposide plus ifosfamide or topotecan. STI571 was diluted in 150 l of H2O and administered on different days, as indicated. Etoposide and ifosfamide were diluted in 200 l of 0.9% sodium chloride, and topotecan was diluted in 150 l of 0.9% sodium chloride. The control group received injections according to the same schedule as experimentally treated mice. All mice were weighed once weekly. Tumor growth was monitored by measuring 2 perpendicular diameters with calipers. Tumor volume (V) and the relative tumor volume (RTV) were calculated as: V = a^2 × b/2, where a is the width (large diameter) and b the length (small diameter) of the tumor in millimeters, and RTV = Vx/Vi, where Vx is the mean tumor volume in cubic millimeters at any given time and Vi is the mean initial tumor volume in cubic millimeters at the start of treatment. Mice were ethically sacrificed when the tumor volume reached 2,500 mm^3 [5].

动物模型：SCLC6, SCLC61, SCLC 74 and SCLC108 small cell lung cancers are injected into Swiss mice (nu/nu, female).

分子量

493.60

分子式

C29H31N7O

CAS

152459-95-5

溶解度

DMSO: 66.9 mM

（ < 1 mg/ml refers to the product slightly soluble or insoluble )

储存条件

store at -80°C

备注

For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months.