SU11274 (PKI-SU11274) is a Met kinase inhibitor with IC50 of 10 nM. c-Met is a prognostic marker and potential therapeutic target in clear cell renal cell carcinoma. c-Met protein was activated in all cell lines, and SU11274 can block proliferation (and colony formation). c-Met inhibition could significantly suppress cell survival and proliferation as well as enhance the radiosensitivity of DU145 cells. SU11274 on DU145 cells may include the inhibition of c-Met signaling, depolarization of the mitochondrial membrane potential, impairment of DNA repair function, abrogation of cell cycle arrest, and enhancement of cell death.
|Cell lines||LoVo cells line|
|Preparation method||MTT assay.
After pancreatic enzymeization, cells were seeded in 96-well plates at 1 9 105/ml (200 ll/well) and allowed to adhere overnight. SU11274, dissolved in 1 % DMSO and diluted in medium, was added at different concentrations 0.1, 0.5, 2.5 μM, 2μl per well. Another 4 wells were set as a reference and incubated for 24, 48 and 72 h. Twenty microliter MTT (5 g/l; Invitrogen, USA) was added, and cells were incubated for another 4 h. The supernatant was removed, 150 ll DMSO was added and oscillated for 10 min avoiding light at room temperature. The assessment procedure was repeated 3 times, and the average value was determined from each well as the absorbance value at 490 nm on a microplate reader.
|Concentrations||0.1, 0.5, 2.5 μM|
|Incubation time||24, 48 and 72 h|
|Animal models||LoVo cells tumor xenograft in 4- to 5-week-old female nude mice (BALB/c-nu/nu)|
|Formulation||1 % DMSO|
|Dosages||0.18, 0.09, 0.0225 mg/kg once daily for 30 days from the day that the tumors became palpable|
|Body Surface Area (m2)||0.007||0.025||0.15||0.05||0.02||0.5|
|Animal A (mg/kg) = Animal B (mg/kg) multiplied by||Animal B Km|
|Animal A Km|
For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for resveratrol of 11.2 mg/kg.
|Solubility||DMSO 90 mg/mL|
|Source||Oncol Lett (2015). Figure 5.SU11274|
|Cell Lines||PK-45H cells|
|Incubation Time||48 h|
|Results||Following treatment with 30 μM SU11274, cell motility was suppressed to 1.0±0.3% in MIA‑Paca2 cells (P<0.05) and 14.7±3.5% in PK‑45H cells (P<0.05) of the level of cells treated with 0 μM SU11274, respectively.|
Study of critical role of c-Met and its inhibitor SU11274 in colorectal carcinoma.
Gao W, et al. Med Oncol. 2013 Jun;30(2):546. PMID: 23536000.
c-Met inhibitor SU11274 enhances the response of the prostate cancer cell line DU145 to ionizing radiation.
Yu H, et al. Biochem Biophys Res Commun. 2012 Sep 28. PMID: 23026049.
c-Met is a prognostic marker and potential therapeutic target in clear cell renal cell carcinoma.
Gibney GT, et al. Ann Oncol. 2012 Sep 28. PMID: 23022995.
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