TSU-68 (SU6668) is an oral tyrosine kinase inhibitor of VEGFR-2, PDGFR and FGFR. TSU-68 inhibits SCF-induced proliferation of MO7E cells with IC50 of 0.29 μM, and induces apoptosis. TSU-68 (SU6668) also inhibits Aurora kinases B and C (IC50 = 35 and 210 nM respectively). TSU68 suppresses tumor growth, blocks angiogenesis in tumors, and induces apoptosis of tumor vasculature and regression of established tumors. In a tumor model of HT29 human colon carcinoma, TSU-68 (200 mg/kg) decreases the average vessel permeability and average fractional plasma volume in the tumor rim and core.
|Cell lines||HUVECs cells|
|Preparation method||HUVECs (seeded at 2 × 106 cells/10-cm plate) were grown to confluence in endothelial cell growth media [containing 12 μg/ml bovine brain extract, 10 μg/ml human epidermal growth factor, 1 μg/ml hydrocortisone, 2% (v/v) FBS, 50 μg/ml gentamicin, and 50 mg/ml amphotericin B in modified MCDB 131 (Clonetics Corp., Walkersville, MD)] and then quiesced in endothelial cell basal media (modified MCDB 131; Clonetics) containing 0.5% FBS for 24 h before drug treatment. All cell lines were incubated with the indicated concentrations of SU6668 for 60 min before ligand stimulation (100 ng/ml) for 10 min. Preparation of cell lysates, separation of cellular proteins (30 μg from NIH-3T3 engineered cells, 100 μg from HUVECs), and immunoblotting with antiphosphotyrosine antibody were performed as described previously.|
|Incubation time||60 min|
|Animal models||A375, Calu-6, A431, C6, and SF763T tumor cells xenograft in athymic mice|
|Dosages||75 or 100 mg/kg|
|Administration||i.p. by bolus injection|
|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 60 mg/mL|
|Source||Cell Physiol Biochem (2017). Figure 3. TSU-68|
|Method||Measurement of VDCC currents|
|Cell Lines||ASM cells|
|Incubation Time||30 min|
|Results||The currents were then removed by 316 μM TSU-68, while 100 μM TSU-68 partially blocked the currents|
TSU68 prevents liver metastasis of colon cancer xenografts by modulating the premetastatic niche.
Yamamoto M, et al. Cancer Res. 2008 Dec 1;68(23):9754-62. PMID: 19047154.
In vivo assessment of antiangiogenic activity of SU6668 in an experimental colon carcinoma model.
Marzola P, et al. Clin Cancer Res. 2004 Jan 15;10(2):739-50. PMID: 14760097.
The antiangiogenic protein kinase inhibitors SU5416 and SU6668 inhibit the SCF receptor (c-kit) in a human myeloid leukemia cell line and in acute myeloid leukemia blasts.
Smolich BD, et al. Blood. 2001 Mar 1;97(5):1413-21. PMID: 11222388.
SU6668 is a potent antiangiogenic and antitumor agent that induces regression of established tumors.
Laird AD, et al. Cancer Res. 2000 Aug 1;60(15):4152-60. PMID: 10945623.
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