Orantinib-SU6668-DataSheet-MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEOrantinibCat. No.: HY-10517CAS No.: 252916-29-3Synonyms: SU6668; TSU-68分式: CHNO分量: 310.35作靶点: PDGFR; VEGFR; FGFR作通路: Protein Tyrosine Kinase/RTK储存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性数据体外实验 DMSO

2、 : 28 mg/mL (90.22 mM)* means soluble, but saturation unknown.Mass Solvent1 mg 5 mg 10 mg Concentration制备储备液1 mM 3.2222 mL 16.1108 mL 32.2217 mL5 mM 0.6444 mL 3.2222 mL 6.4443 mL10 mM 0.3222 mL 1.6111 mL 3.2222 mL请根据产品在不同溶剂中的溶解度，选择合适的溶剂配制储备液，并请注意储备液的保存式和期限。BIOLOGICAL ACTIVITY物活性 Orantinib (SU6668; T

3、SU-68)是多靶点的受体酪氨酸激酶抑制剂，对Flt-1，PDGFR 和FGFR1 的 Ki 值分别为2.1 M，8 nM 和 1.2 M。IC50 & Target Flt-1 PDGFR FGFR12.1 M (Ki) 0.008 M (Ki) 1.2 M (Ki)1/3 Master of Small Molecules 您边的抑制剂师www.MedChemE体外研究 Orantinib (SU6668; 0.03-10 M) shows inhibitory activity against tyrosine phosphorylation of KDR in VEGFstimulat

4、ed HUVECs, and also blocks PDGF-stimulated PDGFR tyrosine phosphorylation in NIH-3T3 cellsoverexpressing PDGFR. Orantinib (10 M) inhibits acidic FGF-induced phosphorylation of the FGFR1substrate 2. However, Orantinib (up to 100 M) has no effect on EGF-stimulated EGFR tyrosinephosphorylation in NIH-3

5、T3 cells overexpressing EGFR. Furthermore, Orantinib inhibits VEGF-driven andFGF-driven mitogenesis of HUVECs with mean IC50 of 0.34 M and 9.6 M, respectively 1. In humanmyeloid leukemia MO7E cells, Orantinib (SU6668) inhibits the tyrosine autophosphorylation of stem cellfactor (SCF) receptor, c-kit

6、, with IC50 of 0.1-1 M, as well as ERK1/2 phosphorylation. In addition, Orantinibsuppresses SCF-induced proliferation of MO7E cells with an IC50 of 0.29 M, and induces apoptosis 2.体内研究 Orantinib (SU6668; 75-200 mg/kg) causes tumor growth inhibition on several tumor types in xenograftmodels in athymi

7、c mice, such as A375, Colo205, H460, Calu-6, C6, SF763T, and SKOV3TP5 cells. Orantinib(75 mg/kg) also inhibits tumor angiogenesis of C6 glioma xenografts 1. In a tumor model of HT29 humancolon carcinoma, Orantinib (200 mg/kg) decreases the average vessel permeability and average fractionalplasma vol

8、ume in the tumor rim and core. Orantinib enhances abnormal stromal development at theperiphery of carcinomas 3. Moreover, Orantinib (TSU-68; 200 mg/kg) augments the effect ofchemotherapeutic infusion in a rabbit VX2 liver tumor model 4.PROTOCOLCell Assay 1 Cells are seeded (3105 cells/35-mm well) in

9、 DMEM containing 10% (v/v) FBS and grow to confluence andthen quiesced in DMEM containing 0.1% serum for 2 hours before drug treatment. HUVECs (seeded at2106 cells/10-cm plate) are grown to confluence in endothelial cell growth media and then quiesced inendothelial cell basal media containing 0.5% F

10、BS for 24 hours before drug treatment. All cell lines areincubated with Orantinib for 1 hour before ligand stimulation (100 ng/mL) for 10 min.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Animal Colo205 and H460 cells are cultured in RPMI 1640 supplem

11、ented with 10% FBS and 2 mm glutamine.Administration 1 SKOV3 cells are passaged five times through mice to yield SKOV3TP5 cells. These cells are cultured inDMEM supplemented with 10% FBS and 2 mm glutamine. Tumor cells (3-10106 cells/animal) are implanteds.c. into the hind flank of mice on day 0. Da

12、ily treatment with Orantinib or vehicle commenced 1 day afterimplantation of cells (to test efficacy against newly implanted tumors) or when tumors have reached apredetermined average size (to test efficacy against established tumors). Orantinib is delivered i.p. by bolusinjection in DMSO or p.o. by

13、 gavage in a cremophor-based vehicle according to the specifics stated in figureand table legends. Tumor growth is measured twice a week using vernier calipers for the duration oftreatment. Tumor volumes are calculated.MCE has not independently confirmed the accuracy of these methods. They are for r

14、eference only.户使本产品发表的科研献 Sci Transl Med. 2018 Jul 18;10(450). pii: eaaq1093. Patent. US20180263995A1.2/3 Master of Small Molecules 您边的抑制剂师www.MedChemESee more customer validations on HYPERLINK / www.MedChemEREFERENCES1. Laird AD, et al. SU6668 is a potent antiangiogenic and antitumor agent that ind

15、uces regression of established tumors. Cancer Res,2000, 60(15), 4152-4160.2. Smolich BD, et al. The antiangiogenic protein kinase inhibitors SU5416 and SU6668 inhibit the SCF receptor (c-kit) in a human myeloidleukemia cell line and in acute myeloid leukemia blasts. Blood, 2001, 97(5), 1413-1421.3.

16、Marzola P, et al. In vivo assessment of antiangiogenic activity of SU6668 in an experimental colon carcinoma model. Clin Cancer Res,2004, 10(2), 739-750.4. Kim HC, et al. Augmentation of chemotherapeutic infusion effect by TSU-68, an oral targeted antiangiogenic agent, in a rabbit VX2 livertumor model. Cardiovas