Regorafenib (BAY 73-4506) is a novel oral multikinase inhibitor of c-KIT, VEGFR2, B-Raf with IC50s of 17, 40 and 69 nM respectively. Regorafenib (BAY 73-4506) administered once orally at 10 mg/kg significantly decreased the extravasation of Gadomer in the vasculature of rat GS9L glioblastoma tumor xenografts.
|Cell lines||GIST 882, TT cells MDA-MB-231, HepG2 and A375 cells|
|Preparation method||Cell proliferation assays For proliferation assays, GIST 882 and TT cells were grown in RPMI medium containing L-glutamine, and MDA-MB-231, HepG2 and A375 cells in DMEM always containing 10% hiFBS. Cells were trypsinized, plated at 5 104 cells/well in 96-well plates in complete media containing 10% FBS and grown overnight at 37 C. The next day, vehicle or regorafenib serially diluted in complete growth media to between 10µM and 5 nM final concentrations, and 0.2% DMSO, was added and incubation was continued for 96 hr. Cell proliferation was quantified using CellTitre-GloTM (Promega Corporation, Madison, WI).|
|Incubation time||96 h|
|Animal models||Mice bearing xenografts of the human CRC cell line Colo-205 (B-RAFV600E), the human BC cell line MDA-MB-231 (K-RASG13D, B-RAFG464V) or the human RCC cell line 786-O (Von-Hippel Lindau gene - /- )|
|Formulation||formulated as a solution in either PEG400/125 mM aqueous methanesulfonic acid (80/20) or polypropylene glycol/PEG400/Pluronic F68 (42.5/42.5/15 þ 20% Aqua)|
|Dosages||100, 30, 10, and 3 mg/ kg qd 21 in the 786-O model, and qd 9 in the Colo-205 and MDA-MB-231 models|
|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.
|Source||Cancer Chemother Pharmacol (2015). Figure 4. Regorafenib|
|Cell Lines||HepG2 cells|
|Incubation Time||48 and 72 h|
|Results||We found that the growth inhibition observed with both drugs was significantly higher when they were used in combination (Fig. 4a). In addition, we saw that Erlotinib 1.25 μM also partially blocked the effects of hPLs in antagonizing Regorafenib-mediated cell growth inhibition (Fig. 4b).|
|Source||Cancer Chemother Pharmacol (2015). Figure 1. Regorafenib|
|Cell Lines||HCC cell lines|
|Incubation Time||48 h|
|Results||As shown in Fig. 1c, after 6 h (T1) from block release, Regorafenib-treated cells in G2/M phase were similar to the control cells at T0, while the number of control cells that proceeded through the cell cycle doubled with respect to the number of cells at T0.|
Regorafenib monotherapy for previously treated metastatic colorectal cancer (CORRECT): an international, multicentre, randomised, placebo-controlled, phase 3 trial.
Grothey A, et al. Lancet. 2013 Jan 26;381(9863):303-12. PMID: 23177514.
Regorafenib (BAY 73-4506) in advanced colorectal cancer: a phase I study.
Strumberg D, et al. Br J Cancer. 2012 May 22;106(11):1722-7. PMID: 22568966.
Regorafenib (BAY 73-4506): a new oral multikinase inhibitor of angiogenic, stromal and oncogenic receptor tyrosine kinases with potent preclinical antitumor activity.
Wilhelm SM, et al. Int J Cancer. 2011 Jul 1;129(1):245-55. PMID: 21170960.
|Related VEGFR/PDGFR Products|
Avapritinib (BLU-285) is a small molecule kinase inhibitor that potently inhibits PDGFRα D842V mutant activity in vitro (IC50 = 0.5 nM) and PDGFRα D842V autophosphorylation in the cellular setting (IC50 = 30 nM); also a potent inhibitor of the analogous KIT mutation, D816V in KIT Exon 17 (IC50 = 0.5 nM).
|Nintedanib Ethanesulfonate Salt
BIBF 1120 esylate is a potent triple angiokinase inhibitor for VEGFR1/2/3, FGFR1/2/3 and PDGFRα/β with IC50s of 34 nM/13 nM/13 nM, 69 nM/37 nM/108 nM and 59 nM/65 nM, respectively.
Regorafenib (BAY 73-4506) is a multi-target inhibitor for VEGFR1, VEGFR2, VEGFR3, PDGFRβ, Kit, RET and Raf-1 with IC50 of 13 nM/4.2 nM/46 nM, 22 nM, 7 nM, 1.5 nM and 2.5 nM, respectively.
|Pazopanib HCl (GW786034 )
Pazopanib HCl (GW786034 HCl) is a novel multi-target inhibitor of VEGFR1, VEGFR2, VEGFR3, PDGFR, FGFR, c-Kit and c-Fms with IC50 of 10 nM, 30 nM, 47 nM, 84 nM, 74 nM, 140 nM and 146 nM in cell-free assays, respectively.
|Dovitinib (TKI-258) Dilactic Acid
Dovitinib Dilactic acid (TKI258 Dilactic acid) is the Dilactic acid of Dovitinib, which is a multitargeted RTK inhibitor, mostly for class III (FLT3/c-Kit) with IC50 of 1 nM/2 nM.
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