Regorafenib (BAY 73-4506)

Name: Regorafenib (BAY 73-4506)
Brand: Selleck Chemicals
SKU: S1178
Rating: 5 (129 reviews)

For research use only.

Catalog No.S1178 Synonyms: Fluoro-Sorafenib, Resihance, Stivarga

129 publications

Regorafenib (BAY 73-4506) Chemical Structure

CAS No. 755037-03-7

Regorafenib (BAY 73-4506, Fluoro-Sorafenib, Resihance, Stivarga) is a multi-target inhibitor for VEGFR1, VEGFR2, VEGFR3, PDGFRβ, Kit (c-Kit), RET (c-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 in cell-free assays, respectively. Regorafenib induces autophagy.

Selleck's Regorafenib (BAY 73-4506) has been cited by 129 publications

Cancer Cell, 2019, 36(2):179-193

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Cell, 2019, 36(2):179-193

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Gastroenterology, 2017, 153(4):1082-1095

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Cancer Res, 2020, 80(21):4815-4827

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Cancers (Basel), 2020, 12(12)E3816

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Front Oncol, 2020, 10:878

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Front Oncol, 2020, 10:563249

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Antiviral Res, 2020, 178:104790

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Arthritis Res Ther, 2020, 22(1):160

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Int J Mol Sci, 2020, 18;21(8):2825

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Cancer Cell Int, 2020, 19;20:58

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Hum Cell, 2020, 10.1007/s13577-020-00420-z

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Hum Cell, 2020, 10.1007/s13577-020-00425-8

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Front Oncol, 2020, 10:694

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Int J Radiat Biol, 2020, 2:1-12

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Front Oncol, 2020, 10:291

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Biochem Biophys Res Commun, 2020, 529(3):699-706

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Onco Targets Ther, 2020, 13:7213-7227

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Nat Cell Biol, 2019, 21(2):203-213

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Gut, 2019, 10.1136/gutjnl-2019-318506

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Cell Rep, 2019, 29(3):573-588

PubMed: 31618628 ( click the link to review the publication )

Br J Pharmacol, 2019, 176(6):787-800

PubMed: 30592786 ( click the link to review the publication )

EBioMedicine, 2019, 41:175-184

PubMed: 30765319 ( click the link to review the publication )

J Med Chem, 2019, 10.1021/acs.jmedchem.9b00855

PubMed: 31364850 ( click the link to review the publication )
Cancers (Basel), 2019, 11(4)

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Cell Death Dis, 2019, 10(10):784

PubMed: 31611551 ( click the link to review the publication )

Cell Death Dis, 2019, 10(9):672

PubMed: 31511501 ( click the link to review the publication )

Br J Cancer, 2019, 120(6):612-620

PubMed: 30792533 ( click the link to review the publication )

Cell Chem Biol, 2019, 10.1016/j.chembiol.2019.04.011

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Mol Cancer Ther, 2019, 18(11):2146-2157

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Cell Commun Signal, 2019, 17(1):85

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Sci Rep, 2019, 9(1):636

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Sci Rep, 2019, 9(1):7103

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Cell Biosci, 2019, 9:88

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Molecules, 2019, 24(7)

PubMed: 30959969 ( click the link to review the publication )

BMC Microbiol, 2019, 19(1):34

PubMed: 30736730 ( click the link to review the publication )

Dis Markers, 2019, 2019:8964015

PubMed: 31781310 ( click the link to review the publication )

FEBS Open Bio, 2019, 9(2):335-347

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Ann Biomed Eng, 2019, 10.1007/s10439-019-02269-2

PubMed: 31020445 ( click the link to review the publication )

Nat Metab, 2019, 1(10):985-995

PubMed: 32021964 ( click the link to review the publication )

Animal Model Exp Med, 2019, 2(4):259-268

PubMed: 31942558 ( click the link to review the publication )

Ann Surg Oncol, 2019, 26(1):139-147

PubMed: 30414038 ( click the link to review the publication )

Mol Cancer Ther, 2018, 17(12):2610-2621

PubMed: 30224431 ( click the link to review the publication )

Endocr Relat Cancer, 2018, 25(4):471-480

PubMed: 29440231 ( click the link to review the publication )

Cancer Sci, 2018, 109(11):3591-3601

PubMed: 30142229 ( click the link to review the publication )

Biochem Biophys Res Commun, 2018, 504(4):878-884

PubMed: 30219235 ( click the link to review the publication )

Anticancer Res, 2018, 38(4):1967-1977

PubMed: 29599312 ( click the link to review the publication )

Chem Sci, 2018, 9(10):2674-2689

PubMed: 29732051 ( click the link to review the publication )
Oncotarget, 2018, 9(56):30869-30882

PubMed: 30112114 ( click the link to review the publication )

BMC Res Notes, 2018, 11(1):859

PubMed: 30514372 ( click the link to review the publication )

Sci Transl Med, 2017, 14;9(394):eaah6144

PubMed: 28615362 ( click the link to review the publication )

Cancer Res, 2017, 77(9):2512-2521

PubMed: 28202514 ( click the link to review the publication )

Arch Toxicol, 2017, 91(8):2921-2938

PubMed: 28032146 ( click the link to review the publication )

Mol Biol Cell, 2017, 28(7):907-921

PubMed: 28209733 ( click the link to review the publication )

Toxicol Sci, 2017, 158(1):213-226

PubMed: 28453775 ( click the link to review the publication )

Sci Rep, 2017, 7(1):1502

PubMed: 28473715 ( click the link to review the publication )

Molecules, 2017, 22(12)

PubMed: 29206199 ( click the link to review the publication )

PLoS One, 2017, 12(3):e0174151

PubMed: 28301591 ( click the link to review the publication )

Curr Cancer Drug Targets, 2017, 17(4):386-401

PubMed: 27396604 ( click the link to review the publication )

Naunyn Schmiedebergs Arch Pharmacol, 2017, 390(11):1125-1134

PubMed: 28779210 ( click the link to review the publication )

Med Sci Monit, 2017, 23:1963-1972

PubMed: 28435150 ( click the link to review the publication )

J Mol Graph Model, 2017,

PubMed: 28236743 ( click the link to review the publication )

Exp Ther Med, 2017, 14(2):1357-1366

PubMed: 28810597 ( click the link to review the publication )

Oncotarget, 2017, 8(4):6102-6113

PubMed: 28008149 ( click the link to review the publication )

Oncotarget, 2017, 8(61):104090-104103

PubMed: 29262623 ( click the link to review the publication )

Oncotarget, 2017, 8(61):103465-103476

PubMed: 29262576 ( click the link to review the publication )

Oncotarget, 2017, 8(69):113444-113459

PubMed: 29371921 ( click the link to review the publication )

Oncotarget, 2017, 8(47):83052-83062

PubMed: 29137323 ( click the link to review the publication )

Oncotarget, 2017, 9(3):3605-3618

PubMed: 29423069 ( click the link to review the publication )

Oncotarget, 2017, 8(52):90262-90277

PubMed: 29163826 ( click the link to review the publication )

Oncotarget, 2017, 8(59):99451-99469

PubMed: 29245915 ( click the link to review the publication )

Oncotarget, 2017, 8(1):1449-1468

PubMed: 27903966 ( click the link to review the publication )
Oncotarget, 2017, 9(17):13154-13166

PubMed: 29568347 ( click the link to review the publication )

Oncotarget, 2017, 8(50):87209-87220

PubMed: 29152075 ( click the link to review the publication )

Oncotarget, 2017, 8(12):18832-18847

PubMed: 27902968 ( click the link to review the publication )

Oncotarget, 2017, 8(10):16367-16386

PubMed: 28146421 ( click the link to review the publication )

Oncotarget, 2017, 8(69):113444-113459

PubMed: 29371921 ( click the link to review the publication )

ACS Nano, 2016, 10(11):9999-10012

PubMed: 27934069 ( click the link to review the publication )

Cancer Res, 2016, 76(1):117-26

PubMed: 26677977 ( click the link to review the publication )

Oncogene, 2016, 10.1038/onc.2016.247

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PLoS Genet, 2016, 12(9):e1006279

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Bioinformatics, 2016, 32(12):i253-i261

PubMed: 27307624 ( click the link to review the publication )

ACS Chem Biol, 2016, 11(12):3400-3411

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J Cell Physiol, 2016, 231(5):1097-105

PubMed: 26419617 ( click the link to review the publication )

Sci Rep, 2016, 6:35308

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J Cell Physiol, 2016, 231(10):2286-302

PubMed: 27187154 ( click the link to review the publication )

Oncotarget, 2016, 7(18):26580-92

PubMed: 27058891 ( click the link to review the publication )

Oncotarget, 2016, 7(11):12975-96

PubMed: 26887051 ( click the link to review the publication )

Oncotarget, 2016, 7(14):17290-300

PubMed: 26981780 ( click the link to review the publication )

Oncotarget, 2016, 7(30):47954-47965

PubMed: 27323830 ( click the link to review the publication )

Oncotarget, 2016, 7(26):40398-40417

PubMed: 27259258 ( click the link to review the publication )

EMBO Mol Med, 2015, 7(10):1350-65

PubMed: 26290450 ( click the link to review the publication )

Proc Natl Acad Sci USA, 2015, 112(6):1839-44

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Int J Cancer, 2015, 136(6):1434-44

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J Exp Clin Cancer Res, 2015, 34:90

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J Cell Physiol, 2015, 230(1):131-9

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J Cell Physiol, 2015, 230(10):2552-78

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J Cell Physiol, 2015, 10.1002/jcp.24961

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Drug Metab Dispos, 2015, 43(12):1934-7

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Cancer Biol Ther, 2015, 16(11):1660-70

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Toxicology, 2015, 327:10-21

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J Med Invest, 2015, 62(3-4):195-8

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Oncotarget, 2015,

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Oncotarget, 2015, 6(7):4745-56

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Oncotarget, 2015, 6(30):28929-37

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Oncotarget, 2015, 6(14):11820-32

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Oncotarget, 2015, 6(27):23281-96

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Gastroenterology, 2015, 148(7):1438-51

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Oncotarget, 2015, 6(4):1954-66

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Oncotarget, 2015, 6(16):14385-98

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Oncotarget, 2015,

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Clin Cancer Res, 2014, 20(22):5745-5755

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Clin Cancer Res, 2014, 20(22):5768-76

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Cell Death Dis, 2014, 5:e1278

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Cancer Cell Int, 2014, 14(1):89

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Cancer Biol Ther, 2014, 15(3):305-16

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Toxicology, 2014, 10.1016/j.tox.2014.11.002

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Drug Des Devel Ther, 2014, 8:1107-23

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Biomed Res Int, 2014, 2014:568693

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Environ Mol Mutagen, 2014, 55(9):704-18

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Mol Med Rep, 2014, 9(1):83-90

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Oncotarget, 2014, 5(12):4071-86

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Rostock University, 2014, Lange F

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Assay Drug Dev Technol, 2014, 12(9-10):514-26

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J Clin Endocrinol Metab, 2013, 98(6):2502-12

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Mol Pharmacol, 2013, 84(4):562-71

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PLoS One, 2013, 8(5):e63240

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J Interferon Cytokine Res, 2013, 33(4):211-25

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Methods Mol Biol, 2011, 685:91-109

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Purity & Quality Control

Choose Selective VEGFR Inhibitors

Biological Activity

Description

Targets

RET ^[1] (Cell-free assay)	Raf-1 ^[1] (Cell-free assay)	VEGFR2 ^[1] (Cell-free assay)	Kit ^[1] (Cell-free assay)	VEGFR1 ^[1] (Cell-free assay)	View More
1.5 nM	2.5 nM	4.2 nM	7 nM	13 nM	View More

In vitro

Regorafenib strongly prevents VEGFR2 autophosphorylation in NIH-3T3/VEGFR2 cells with IC50 of 3 nM. In HAoSMCs, regorafenib suppress PDGFR-β autophosphorylation after stimulation with PDGF-BB, with an IC50 of 90 nM. Regorafenib also inhibits FGFR signaling in MCF-7 breast cancer (BC) cells stimulated with FGF10. Regorafenib very potently inhibited the mutant receptors KIT^K642E and RET^C634W, with IC50 of approximately 20 nM and 10 nM, respectively. Regorafenib inhibits the proliferation of VEGF¹⁶⁵-stimulated HUVECs, with an IC50 of approximately 3 nM. Regorafenib prevents the proliferation of FGF2-stimulated HUVECs and of PDGF-BB-stimulated HAoSMCs with IC50 of 127 nM and 146 nM, respectively. ^[1] Regorafenib targets both tumor cell proliferation and tumor vasculature through inhibition of receptors of tyrosine kinases (VEGFR, KIT, RET, FGFR, and PDGFR) and serine/threonine kinases (Raf and p38MAPK). ^[2] Regorafenib suppresses growth of human Hep3B, PLC/PRF/5 and HepG2 cells in a concentration- and time-dependent manner. ^[3]

Cell Data

Cell Lines	Assay Type	Concentration	Incubation Time	Formulation	Activity Description	PMID
Hep3B	MkjWRZBweHSxc3nzJGF{e2G7	M3HvWVHjiJN3wrFOwG0>	NEXLPJU1QCCq		MnjxbY5pcWKrdIOgZ4VtdCCpcn;3eIg>	MYm8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPjN{OU[wPEc,OjZ\|Mkm2NFg9N2F-
PLC/PRF/5	M{fTVGFxd3C2b4Ppd{BCe3OjeR?=	NVz0VVN4OeLCk{ZCpO69VQ>?	NWq0em9OPDhiaB?=		MkTWbY5pcWKrdIOgZ4VtdCCpcn;3eIg>	MljiQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjZ\|Mkm2NFgoRjJ4M{K5OlA5RC:jPh?=
HepG2	NF2yepBCeG:ydH;zbZMhSXO\|YYm=	MXKx5qCUPcLizszN	NVzFXoNDPDhiaB?=		Mk[0bY5pcWKrdIOgZ4VtdCCpcn;3eIg>	MoTVQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjZ\|Mkm2NFgoRjJ4M{K5OlA5RC:jPh?=
HEK293	MX;GeY5kfGmxbjDBd5NigQ>?	NH\0VVExNjYkgJpOwG0>	NHfQZmEzNzRxNjDo		NIHmNZFz\WS3Y3XzJGdTWDd6IHX4dJJme3Orb36=	MYG8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPTh3OECzNkc,OjV6NUiwN\|I9N2F-
GEO	MU\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?	NFzoeIoxNjBzLUKwJO69VQ>?	NHiz[3A6PiCq	M4nBUWROW09?	NVXlSnJ1cW6qaXLpeJMh[2WubDDndo94fGhiaX6gZUBld3OnLXTldIVv\GWwdDDtZY5v\XJ?	MXm8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPTh\|OEO5NUc,OjV6M{izPVE9N2F-
SW48	MUPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?	Mn7iNE4xOS1{MDFOwG0>	M4PS[Fk3KGh?	NUfoNW5jTE2VTx?=	NG\mSWJqdmirYnn0d{Bk\WyuIHfyc5d1cCCrbjDhJIRwe2VvZHXw[Y5l\W62IH3hco5meg>?	NUXjPWRPRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkW4N\|g{QTFpPkK1PFM5OzlzPD;hQi=>
HT29	MX\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?	NXLnRmtVOC5yMT2yNEDPxE1?	NUfaTmk6QTZiaB?=	NUP2SItCTE2VTx?=	NI\OWYpqdmirYnn0d{Bk\WyuIHfyc5d1cCCrbjDhJIRwe2VvZHXw[Y5l\W62IH3hco5meg>?	NXi2SGFbRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkW4N\|g{QTFpPkK1PFM5OzlzPD;hQi=>
SW480	NUewfGVVT3Kxd4ToJGlvcGmkaYTpc44hSXO\|YYm=	MUewMlAyNTJyIN88US=>	MlraPVYhcA>?	NXfSblZ[TE2VTx?=	M2PnZ4lvcGmkaYTzJINmdGxiZ4Lve5RpKGmwIHGg[I9{\S2mZYDlcoRmdnRibXHucoVz	MnvIQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjV6M{izPVEoRjJ3OEO4N\|kyRC:jPh?=
SW620	NWHFV3RFT3Kxd4ToJGlvcGmkaYTpc44hSXO\|YYm=	M3jGe\|AvODFvMkCg{txO	NXnRdWc6QTZiaB?=	M3n4R2ROW09?	MYHpcohq[mm2czDj[YxtKGe{b4f0bEBqdiCjIHTvd4Uu\GWyZX7k[Y51KG2jbn7ldi=>	NHnaZpU9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NUizPFM6OSd-MkW4N\|g{QTF:L3G+
HCT116	NF7QTWdIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=	NIPwcJgxNjBzLUKwJO69VQ>?	NEOx[YI6PiCq	NIDzT4NFVVOR	NILLTplqdmirYnn0d{Bk\WyuIHfyc5d1cCCrbjDhJIRwe2VvZHXw[Y5l\W62IH3hco5meg>?	NWPzfYVCRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkW4N\|g{QTFpPkK1PFM5OzlzPD;hQi=>
LOVO	M{TB[Wdzd3e2aDDJcohq[mm2aX;uJGF{e2G7	Mmm5NE4xOS1{MDFOwG0>	NHq1cJE6PiCq	NH\LSWlFVVOR	NVnXb4Z5cW6qaXLpeJMh[2WubDDndo94fGhiaX6gZUBld3OnLXTldIVv\GWwdDDtZY5v\XJ?	M{DUblxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ3OEO4N\|kyLz5{NUizPFM6OTxxYU6=
HCT150	MYHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?	M{O2U\|AvODFvMkCg{txO	M{H2UVk3KGh?	NFfBfnpFVVOR	MnTNbY5pcWKrdIOgZ4VtdCCpcn;3eIghcW5iYTDkc5NmNWSncHXu[IVvfCCvYX7u[ZI>	NWrv[oZ{RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkW4N\|g{QTFpPkK1PFM5OzlzPD;hQi=>
SW48-CR	NF\sVJZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=	MX6wMlAyNTJyIN88US=>	NWeyZ\|N2QTZiaB?=	MUXEUXNQ	MVfpcohq[mm2czDj[YxtKGe{b4f0bEBqdiCjIHTvd4Uu\GWyZX7k[Y51KG2jbn7ldi=>	MmizQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjV6M{izPVEoRjJ3OEO4N\|kyRC:jPh?=
GEO-CR	MnnUS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?	NGG5ZoQxNjBzLUKwJO69VQ>?	NUexOJZxQTZiaB?=	MUfEUXNQ	NEX5VHRqdmirYnn0d{Bk\WyuIHfyc5d1cCCrbjDhJIRwe2VvZHXw[Y5l\W62IH3hco5meg>?	M2DKZVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ3OEO4N\|kyLz5{NUizPFM6OTxxYU6=
KB-31	M4XTdGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7				MoXXTWM2OD13LkZCtVAvOyCwTR?=	Mn\YQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjV5NUOzOlEoRjJ3N{WzN\|YyRC:jPh?=
KB-G2	NWj6bm9IT3Kxd4ToJGlvcGmkaYTpc44hSXO\|YYm=				Mof4TWM2OD17LkJCtVAvOSCwTR?=	M3r4NFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ3N{WzN\|YyLz5{NUe1N\|M3OTxxYU6=
LLC-PK1	NV3lcYVKT3Kxd4ToJGlvcGmkaYTpc44hSXO\|YYm=				MWLJR\|UxRTR{LkFCtVMvOiCwTR?=	MmfzQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjV5NUOzOlEoRjJ3N{WzN\|YyRC:jPh?=
LLC-PK1/MRP2	NXK5TpQ5T3Kxd4ToJGlvcGmkaYTpc44hSXO\|YYm=				Mn65TWM2OD16Mj60xtEzNjdibl2=	NVfoXlFURGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkW3OVM{PjFpPkK1O\|U{OzZzPD;hQi=>
HEK293	NYTyOJVTT3Kxd4ToJGlvcGmkaYTpc44hSXO\|YYm=				MUPJR\|UxRTFzLkFCtVEvOiCwTR?=	M2jx[lxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ3N{WzN\|YyLz5{NUe1N\|M3OTxxYU6=
HEK293/OATP1B1	NU\vXVUzT3Kxd4ToJGlvcGmkaYTpc44hSXO\|YYm=				NVjCT2tWUUN3ME22MlLDuTBwMzDuUS=>	NEXxZmQ9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NUe1N\|M3OSd-MkW3OVM{PjF:L3G+
HROC18	MljjS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?				MWPJR\|UxRTFwMzFOwG0>	MX[8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPTNyOUmxOEc,OjV\|MEm5NVQ9N2F-
HROC24	MXvHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?				NHq5XWJKSzVyPUSuOkDPxE1?	M334UVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ3M{C5PVE1Lz5{NUOwPVkyPDxxYU6=
HROC43	MVXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?				MneyTWM2OD13LkOg{txO	NGXrfVA9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NUOwPVkyPCd-MkWzNFk6OTR:L3G+
HROC46	M1zsb2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7				M1nPbGlEPTB;Mj60JO69VQ>?	MkO4QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjV\|MEm5NVQoRjJ3M{C5PVE1RC:jPh?=
RJ345	MW\GeY5kfGmxbjDBd5NigQ>?	NGXidWkxNjVxNTFOwG0>	NHLuPVkzPCCq	MkX0SG1UVw>?	NYTyS4hqcW6qaXLpeJMhfGinIHPlcIwhdWmpcnH0bY9v	NHXWe\|g9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NUK1N\|k6PCd-MkWyOVM6QTR:L3G+
RJ348	NXu5c3pUTnWwY4Tpc44hSXO\|YYm=	MUCwMlUwPSEQvF2=	NV73ZZc3OjRiaB?=	MVLEUXNQ	NEPtXmlqdmirYnn0d{B1cGViY3XscEBucWe{YYTpc44>	NGe4ToU9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NUK1N\|k6PCd-MkWyOVM6QTR:L3G+
MCF-7	NH\5WZdHfW6ldHnvckBCe3OjeR?=	MW[wMlUwPSEQvF2=	NFfmNJMzPCCq	NGTCNYRFVVOR	M{\KWYlvcGmkaYTzJJRp\SClZXzsJI1q\3KjdHnvci=>	NX;Nc\|c2RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkWyOVM6QTRpPkK1NlU{QTl2PD;hQi=>
MDA-MB-231	M3qzRmZ2dmO2aX;uJGF{e2G7	MXWwMlUwPSEQvF2=	MU[yOEBp	NGS1c\|JFVVOR	MV3pcohq[mm2czD0bIUh[2WubDDtbYdz[XSrb36=	NUDV[WFCRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkWyOVM6QTRpPkK1NlU{QTl2PD;hQi=>
HT15	MV\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?	MmXyNU0zOCEQvF2=	MUS0PEBp		NEDC[5VqdmirYnn0d{Bk\WyuIHfyc5d1cCCrbjDhJIRwe2VvZHXw[Y5l\W62IH3hco5meg>?	Mnq3QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjVyN{GwNVgoRjJ3MEexNFE5RC:jPh?=
DLD1	MX7Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?	M1;NRlEuOjBizszN	MoLTOFghcA>?		M4nGVYlvcGmkaYTzJINmdGxiZ4Lve5RpKGmwIHGg[I9{\S2mZYDlcoRmdnRibXHucoVz	MXi8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPTB5MUCxPEc,OjVyN{GwNVg9N2F-
HT-29	MYLHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?	M17VZVEuOjBizszN	NFvYOHk1QCCq		MX;pcohq[mm2czDj[YxtKGe{b4f0bEBqdiCjIHTvd4Uu\GWyZX7k[Y51KG2jbn7ldi=>	NXHzZWlqRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkWwO\|ExOThpPkK1NFcyODF6PD;hQi=>
Hct-116	NWrEXJBQT3Kxd4ToJGlvcGmkaYTpc44hSXO\|YYm=	MlHDNU0zOCEQvF2=	MnnGOFghcA>?		NFfEfY9qdmirYnn0d{Bk\WyuIHfyc5d1cCCrbjDhJIRwe2VvZHXw[Y5l\W62IH3hco5meg>?	MmPqQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjVyN{GwNVgoRjJ3MEexNFE5RC:jPh?=
HT15	M4CzemFxd3C2b4Ppd{BCe3OjeR?=	NYq4S3dFOS1zMDFOwG0>	Ml;oOFghcA>?		MWrpcoR2[2W\|IHPlcIwh\GWjdHigbY4h[SCmb4PlMYRmeGWwZHXueEBu[W6wZYK=	M3i2TFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ3MEexNFE5Lz5{NUC3NVAyQDxxYU6=
DLD1	NVjRboo6SXCxcITvd4l{KEG\|c3H5	NVT0TpFSOS1zMDFOwG0>	NGfMUmg1QCCq		MXvpcoR2[2W\|IHPlcIwh\GWjdHigbY4h[SCmb4PlMYRmeGWwZHXueEBu[W6wZYK=	MYW8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPTB5MUCxPEc,OjVyN{GwNVg9N2F-
HT-29	M2fHTWFxd3C2b4Ppd{BCe3OjeR?=	NYjIe4doOS1zMDFOwG0>	NHPVWJI1QCCq		NHfmbIpqdmS3Y3XzJINmdGxiZHXheIghcW5iYTDkc5NmNWSncHXu[IVvfCCvYX7u[ZI>	M1THRlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ3MEexNFE5Lz5{NUC3NVAyQDxxYU6=
Hct-116	NGHM[YZCeG:ydH;zbZMhSXO\|YYm=	NUPBS2RLOS1zMDFOwG0>	NXnWdHhNPDhiaB?=		NWDDUGlHcW6mdXPld{Bk\WyuIHTlZZRpKGmwIHGg[I9{\S2mZYDlcoRmdnRibXHucoVz	M{XrdFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ3MEexNFE5Lz5{NUC3NVAyQDxxYU6=
GBM5	NHTPOGxCeG:ydH;zbZMhSXO\|YYm=	M13zU\|AvPeLCk{GuNQKBkc7:TR?=	MUmyOEBp	MmPVSG1UVw>?	NGDrXnpqdnSncnHjeJMhf2m2aDDsZZBifGmwaXKgeI8hcW6mdXPlJINmdGxiZHXheIg>	NH\oSZE9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NEmxNVIyPSd-MkS5NVEzOTV:L3G+
GBM6	NInaNGNCeG:ydH;zbZMhSXO\|YYm=	MoS1NE426oDVMT6w5qCK\|ryP	NH;TdZMzPCCq	MVnEUXNQ	NXK4bHRucW62ZYLhZ5R{KHerdHigcIFx[XSrbnniJJRwKGmwZIXj[UBk\WyuIHTlZZRp	Mn\hQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjR7MUGyNVUoRjJ2OUGxNlE2RC:jPh?=
GBM12	M{K4N2Fxd3C2b4Ppd{BCe3OjeR?=	NWTER5BWOC534pETNU4x6oDLzszN	M1rrVFI1KGh?	MmLKSG1UVw>?	MVXpcpRmemGldIOge4l1cCCuYYDheIlvcWJidH:gbY5lfWOnIHPlcIwh\GWjdHi=	M3fnXFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ2OUGxNlE2Lz5{NEmxNVIyPTxxYU6=
GBM14	NXTq[GY2SXCxcITvd4l{KEG\|c3H5	M1PKbVAvPeLCk{GuNQKBkc7:TR?=	MkHFNlQhcA>?	M1LCTGROW09?	M2rE[4lvfGW{YXP0d{B4cXSqIHzhdIF1cW6rYjD0c{BqdmS3Y3WgZ4VtdCCmZXH0bC=>	NHjzUY89[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NEmxNVIyPSd-MkS5NVEzOTV:L3G+
Hep3B	NGnBWW1Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?=	MU[x5qCUOi53wrFOwG0>	Mlu1NlQwPDhxN{KgbC=>		NXzPVWsycW6qaXLpeJMh[2WubDDndo94fGh?	NXzqbIlvRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkS4PFU5QTBpPkK0PFg2QDlyPD;hQi=>
PLC/PRF/5	NVG3Ono4T3Kxd4ToJGlvcGmkaYTpc44hSXO\|YYm=	NYXlS\|NoOeLCk{KuOeKh\|ryP	Mn:1NlQwPDhxN{KgbC=>		NYXSN3FncW6qaXLpeJMh[2WubDDndo94fGh?	M4TyWlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ2OEi1PFkxLz5{NEi4OVg6ODxxYU6=
HepG2	MlHrS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?	NGnRVZEy6oDVMj61xsDPxE1?	M3jJbFI1NzR6L{eyJIg>		M3rsT4lvcGmkaYTzJINmdGxiZ4Lve5Rp	NFLCTG09[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NEi4OVg6OCd-MkS4PFU5QTB:L3G+
HCT116	MV7GeY5kfGmxbjDBd5NigQ>?	MXOxNE8zOC92MDFOwG0>	NWHETHhDOjRiaB?=		M4fJeolv\HWlZYOgVHVOSSCycn;0[YlvKGGwZDDtVm5CKGW6cILld5Nqd25iaX6gZUBld3OnLTDhcoQhfGmvZT3k[ZBmdmSnboSgcYFvdmW{	M1XOTFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ2N{[zOlEyLz5{NEe2N\|YyOTxxYU6=
Lim2405	MUfGeY5kfGmxbjDBd5NigQ>?	NWLmcoJ2PDBizszN	MkLlNlQhcA>?		MmTtbY5lfWOnczDQWW1CKHC{b4TlbY4h[W6mIHPlcIwh[XCxcITvd4l{	NVXENpFXRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkS3OlM3OTFpPkK0O\|Y{PjFzPD;hQi=>
LoVo	M1zlVWZ2dmO2aX;uJGF{e2G7	M3u1OlQxKM7:TR?=	M4C3RlI1KGh?		NVG5eHY{cW6mdXPld{BRXU2DIIDyc5RmcW5iYX7kJINmdGxiYYDvdJRwe2m\|	MmTMQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjR5NkO2NVEoRjJ2N{[zOlEyRC:jPh?=
Lim1215	MU\GeY5kfGmxbjDBd5NigQ>?	NYi5SIFTPDBizszN	M2CyN\|I1KGh?		MXLpcoR2[2W\|IGDVUWEheHKxdHXpckBidmRiY3XscEBieG:ydH;zbZM>	MXy8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPDd4M{[xNUc,OjR5NkO2NVE9N2F-
SW48	M2HHO2Z2dmO2aX;uJGF{e2G7	MYK0NEDPxE1?	MmftNlQhcA>?		MnO4bY5lfWOnczDQWW1CKHC{b4TlbY4h[W6mIHPlcIwh[XCxcITvd4l{	MnzFQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjR5NkO2NVEoRjJ2N{[zOlEyRC:jPh?=
RKO	Mmj2SpVv[3Srb36gRZN{[Xl?	MVi0NEDPxE1?	M1G2NFI1KGh?		NXLFS5JucW6mdXPld{BRXU2DIIDyc5RmcW5iYX7kJINmdGxiYYDvdJRwe2m\|	NGnHfXU9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NEe2N\|YyOSd-MkS3OlM3OTF:L3G+
SW837	NE\UT4ZHfW6ldHnvckBCe3OjeR?=	MX20NEDPxE1?	NEHrc3EzPCCq		NYLCOmZscW6mdXPld{BRXU2DIIDyc5RmcW5iYX7kJINmdGxiYYDvdJRwe2m\|	NH7Ufog9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NEe2N\|YyOSd-MkS3OlM3OTF:L3G+
SW1463	NUfn[oNNTnWwY4Tpc44hSXO\|YYm=	NWHN[Y1DPDBizszN	NX[0[lBwOjRiaB?=		MnOzbY5lfWOnczDQWW1CKHC{b4TlbY4h[W6mIHPlcIwh[XCxcITvd4l{	NHX6O4U9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NEe2N\|YyOSd-MkS3OlM3OTF:L3G+
SW480	MlL1SpVv[3Srb36gRZN{[Xl?	NYLEemVoPDBizszN	MoDJNlQhcA>?		M4D0colv\HWlZYOgVHVOSSCycn;0[YlvKGGwZDDj[YxtKGGyb4D0c5Nqew>?	MVG8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPDd4M{[xNUc,OjR5NkO2NVE9N2F-
Vaco432	NHu1V3NHfW6ldHnvckBCe3OjeR?=	NHvCe2Y1OCEQvF2=	NHXxVnozPCCq		MmXBbY5lfWOnczDQWW1CKHC{b4TlbY4h[W6mIHPlcIwh[XCxcITvd4l{	NWDCSHZXRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkS3OlM3OTFpPkK0O\|Y{PjFzPD;hQi=>
Vaco400	NYLXdnRDTnWwY4Tpc44hSXO\|YYm=	NIfB[IU1OCEQvF2=	MV6yOEBp		MlvObY5lfWOnczDQWW1CKHC{b4TlbY4h[W6mIHPlcIwh[XCxcITvd4l{	M2C0b\|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ2N{[zOlEyLz5{NEe2N\|YyOTxxYU6=
DLD1	NH7oe4ZHfW6ldHnvckBCe3OjeR?=	NHntN5Q1OCEQvF2=	NIHKcIYzPCCq		NHnFfWFqdmS3Y3XzJHBWVUFicILveIVqdiCjbnSgZ4VtdCCjcH;weI9{cXN?	NW[yc25QRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkS3OlM3OTFpPkK0O\|Y{PjFzPD;hQi=>
HT29	NVfNN4RITnWwY4Tpc44hSXO\|YYm=	MmqwOFAh\|ryP	MXmyOEBp		MUXpcoR2[2W\|IGDVUWEheHKxdHXpckBidmRiY3XscEBieG:ydH;zbZM>	MXe8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPDd4M{[xNUc,OjR5NkO2NVE9N2F-
PLC/PRF/5	NHvqPXFIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=	NXnNWod6OeLCk{ZCuW0>	NXf6R\|RUOjRxNEivO\|IhcA>?		M4C4UolvcGmkaYTzJINmdGxiZ4Lve5Rp	Mn;nQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjNzNkmxOFgoRjJ\|MU[5NVQ5RC:jPh?=
HepG2	M3vDfGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7	M2m1Z\|HjiJN3wsXN	NX[1bnlFOjRxNEivO\|IhcA>?		NUfuSHpycW6qaXLpeJMh[2WubDDndo94fGh?	NWjVempQRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkOxOlkyPDhpPkKzNVY6OTR6PD;hQi=>
Hep3B	MkDMS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?	M37h[VHjiJN3wsXN	MlfwNlQwPDhxN{KgbC=>		NYHQfIZLcW6qaXLpeJMh[2WubDDndo94fGh?	M2jURlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ\|MU[5NVQ5Lz5{M{G2PVE1QDxxYU6=
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BA/F3	NFvFd5pEgXSxdH;4bYNqfHliYYPzZZk>		M{TrfVczKGi{cx?=		NFfXVFREgXSxdH;4bYNqfHliaX6gcY92e2VicHHy[Y51[WxiQlGvSlMh[2WubIOgbY5kfWKjdHXkJIZweiB5MjDodpMh[nliTWTTJIF{e2G7LDDHTVUxKD1iOT65OVMh\|ryPLh?=	M1fLTVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzNyMkC0OFQyLz5\|MEKwOFQ1OTxxYU6=
U-2 OS	M1K3cZFJXFNiYYPzZZk>				MXnxTHRUKG:oIIDl[IlifHKrYzDjZY5k\XJiY3XscEBtcW6nczD0c{Bq\GWwdHnmfUBufWy2aYDs[UBweHCxcoT1col1cWW\|IH\vdkBlenWpIILldJVzeG:\|aX7nPkBRemmvYYL5JJNkemWnbjDmc5IhXS1{IF;TJINmdGy\|	M2LpdlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7NEO1NVM6Lz5{OUSzOVE{QTxxYU6=
A673	NVXPd3o4eUiWUzDhd5NigQ>?				Mn[0dWhVWyCxZjDw[YRq[XS{aXOgZ4Fv[2W{IHPlcIwhdGmwZYOgeI8hcWSnboTp[pkhdXWudHnwcIUhd3Cyb4L0eY5qfGmnczDmc5Ih\HK3ZzDy[ZB2enCxc3nu[\|ohWHKrbXHyfUB{[3KnZX6g[o9zKEF4N{OgZ4VtdHN?	NWHJUmFnRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkm0N\|UyOzlpPkK5OFM2OTN7PD;hQi=>
DAOY	NWfwdVBUeUiWUzDhd5NigQ>?				NILBfYZyUFSVIH;mJJBm\GmjdILpZ{Bk[W6lZYKgZ4VtdCCuaX7ld{B1dyCrZHXueIlngSCvdXz0bZBt\SCxcIDvdpR2dmm2aXXzJIZweiCmcoXnJJJmeHW{cH;zbY5oQiCScnntZZJ6KHOlcnXlckBnd3JiRFHPXUBk\Wyucx?=	NUPYU4ZyRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkm0N\|UyOzlpPkK5OFM2OTN7PD;hQi=>
Saos-2	NIDZWW5yUFSVIHHzd4F6				MoHudWhVWyCxZjDw[YRq[XS{aXOgZ4Fv[2W{IHPlcIwhdGmwZYOgeI8hcWSnboTp[pkhdXWudHnwcIUhd3Cyb4L0eY5qfGmnczDmc5Ih\HK3ZzDy[ZB2enCxc3nu[\|ohWHKrbXHyfUB{[3KnZX6g[o9zKFOjb4OtNkBk\Wyucx?=	MlL2QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjl2M{WxN\|koRjJ7NEO1NVM6RC:jPh?=
BT-37	NVOwSlNzeUiWUzDhd5NigQ>?				MUXxTHRUKG:oIIDl[IlifHKrYzDjZY5k\XJiY3XscEBtcW6nczD0c{Bq\GWwdHnmfUBufWy2aYDs[UBweHCxcoT1col1cWW\|IH\vdkBlenWpIILldJVzeG:\|aX7nPkBRemmvYYL5JJNkemWnbjDmc5IhSlRvM{egZ4VtdHN?	MV[8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTR\|NUGzPUc,Ojl2M{WxN\|k9N2F-
RD	M1H5PZFJXFNiYYPzZZk>				MWPxTHRUKG:oIIDl[IlifHKrYzDjZY5k\XJiY3XscEBtcW6nczD0c{Bq\GWwdHnmfUBufWy2aYDs[UBweHCxcoT1col1cWW\|IH\vdkBlenWpIILldJVzeG:\|aX7nPkBRemmvYYL5JJNkemWnbjDmc5IhWkRiY3XscJM>	MVG8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTR\|NUGzPUc,Ojl2M{WxN\|k9N2F-
BT-12	M4r4W5FJXFNiYYPzZZk>				NUXHfldxeUiWUzDv[kBx\WSrYYTybYMh[2GwY3XyJINmdGxibHnu[ZMhfG9iaXTlcpRq\nlibYXseIlxdGVib4Dwc5J1fW6rdHnld{Bnd3JiZIL1[{Bz\XC3coDvd4lv\zpiUILpcYFzgSC\|Y4Ll[Y4h\m:{IFLUMVEzKGOnbHzz	NFTqeHM9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUSzOVE{QSd-Mkm0N\|UyOzl:L3G+
MG 63 (6-TG R)	M372TpFJXFNiYYPzZZk>				NWfDOWlCeUiWUzDv[kBx\WSrYYTybYMh[2GwY3XyJINmdGxibHnu[ZMhfG9iaXTlcpRq\nlibYXseIlxdGVib4Dwc5J1fW6rdHnld{Bnd3JiZIL1[{Bz\XC3coDvd4lv\zpiUILpcYFzgSC\|Y4Ll[Y4h\m:{IF3HJFY{KCh4LWTHJHIqKGOnbHzz	MXG8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTR\|NUGzPUc,Ojl2M{WxN\|k9N2F-
NB1643	NHHsd45yUFSVIHHzd4F6				NVHTUnZmeUiWUzDv[kBx\WSrYYTybYMh[2GwY3XyJINmdGxibHnu[ZMhfG9iaXTlcpRq\nlibYXseIlxdGVib4Dwc5J1fW6rdHnld{Bnd3JiZIL1[{Bz\XC3coDvd4lv\zpiUILpcYFzgSC\|Y4Ll[Y4h\m:{IF7CNVY1OyClZXzsdy=>	NXLYSFBpRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkm0N\|UyOzlpPkK5OFM2OTN7PD;hQi=>
OHS-50	MXLxTHRUKGG\|c3H5				NVXsRnZReUiWUzDv[kBx\WSrYYTybYMh[2GwY3XyJINmdGxibHnu[ZMhfG9iaXTlcpRq\nlibYXseIlxdGVib4Dwc5J1fW6rdHnld{Bnd3JiZIL1[{Bz\XC3coDvd4lv\zpiUILpcYFzgSC\|Y4Ll[Y4h\m:{IF;IV{02OCClZXzsdy=>	NYPDbnQ3RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkm0N\|UyOzlpPkK5OFM2OTN7PD;hQi=>
SJ-GBM2	NXni[49keUiWUzDhd5NigQ>?				NUH2[2x2eUiWUzDv[kBx\WSrYYTybYMh[2GwY3XyJINmdGxibHnu[ZMhfG9iaXTlcpRq\nlibYXseIlxdGVib4Dwc5J1fW6rdHnld{Bnd3JiZIL1[{Bz\XC3coDvd4lv\zpiUILpcYFzgSC\|Y4Ll[Y4h\m:{IGPKMWdDVTJiY3XscJM>	MoTyQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjl2M{WxN\|koRjJ7NEO1NVM6RC:jPh?=
SK-N-MC	NHz3cotyUFSVIHHzd4F6				NH3lco9yUFSVIH;mJJBm\GmjdILpZ{Bk[W6lZYKgZ4VtdCCuaX7ld{B1dyCrZHXueIlngSCvdXz0bZBt\SCxcIDvdpR2dmm2aXXzJIZweiCmcoXnJJJmeHW{cH;zbY5oQiCScnntZZJ6KHOlcnXlckBnd3JiU1utUk1OSyClZXzsdy=>	M4\r[lxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7NEO1NVM6Lz5{OUSzOVE{QTxxYU6=
NB-EBc1	NHvJSIxyUFSVIHHzd4F6				MXfxTHRUKG:oIIDl[IlifHKrYzDjZY5k\XJiY3XscEBtcW6nczD0c{Bq\GWwdHnmfUBufWy2aYDs[UBweHCxcoT1col1cWW\|IH\vdkBlenWpIILldJVzeG:\|aX7nPkBRemmvYYL5JJNkemWnbjDmc5IhVkJvRVLjNUBk\Wyucx?=	NXPMcpduRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkm0N\|UyOzlpPkK5OFM2OTN7PD;hQi=>
LAN-5	MmL2dWhVWyCjc4PhfS=>				MXXxTHRUKG:oIIDl[IlifHKrYzDjZY5k\XJiY3XscEBtcW6nczD0c{Bq\GWwdHnmfUBufWy2aYDs[UBweHCxcoT1col1cWW\|IH\vdkBlenWpIILldJVzeG:\|aX7nPkBRemmvYYL5JJNkemWnbjDmc5IhVEGQLUWgZ4VtdHN?	MXq8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTR\|NUGzPUc,Ojl2M{WxN\|k9N2F-
Rh18	NXH5cm8xeUiWUzDhd5NigQ>?				MkTGdWhVWyCxZjDw[YRq[XS{aXOgZ4Fv[2W{IHPlcIwhdGmwZYOgeI8hcWSnboTp[pkhdXWudHnwcIUhd3Cyb4L0eY5qfGmnczDmc5Ih\HK3ZzDy[ZB2enCxc3nu[\|ohWHKrbXHyfUB{[3KnZX6g[o9zKFKqMUigZ4VtdHN?	MUG8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTR\|NUGzPUc,Ojl2M{WxN\|k9N2F-

... Click to View More Cell Line Experimental Data

Assay

Methods	Test Index	PMID
Western blot	PUMA / p53; PubMed: 24763611 Clin Cancer Res WT and p53-KO HCT116 cells were treated with 40 μmol/L regorafenib for 24 hours. PUMA expression was analyzed by Western blotting. Bim / Bid / Bak / Bcl-Xl / Mcl-1; PubMed: 24763611 Clin Cancer Res The expression of indicated Bcl-2 family members was analyzed by Western blotting in HCT116 cells treated with 40 μmol/L regorafenib at indicated time points. p-p65(S536) / p65; PubMed: 24763611 Clin Cancer Res HCT116 cells were treated with 40 μmol/L regorafenib. Expression of p-p65 (S536) and β-actin at indicated time points was analyzed by Western blotting. p-FGFR2 / p-FRS2α / p-AKT / p-MAPK / p-P90RSK / FGFR2 / AKT / MAPK / p90RSK; PubMed: 29573334 Mol Oncol Changes in FGFR2 signaling molecules after regorafenib treatment. Immunoblotting assays were performed after treatment with increasing concentrations of regorafenib for 24 h. Cyclin D / Cyclin E / Cyclin A / Cyclin B / p27 / p21; PubMed: 29573334 Mol Oncol Changes in cell cycle and/or apoptosis‐related molecules. p-STAT3 / STAT3 / PARP / Caspase-9; PubMed: 25071018 Oncotarget p-STAT3(Tyr705), STAT3, the cleaved fragments of PARP and the cleaved fragments of caspase-9 were measured by western blotting at the times indicated after Hct-15 and DLD1 cells were treated with regorafenib at 5 μM. β-actin was used as a loading control. The cleaved fragments of PARP and the cleaved fragments of caspase-9 were indicated by arrows.	24763611 29573334 25071018
Immunofluorescence	p65; PubMed: 24763611 Clin Cancer Res HCT116 cells were treated with 40 μmol/L regorafenib for 3 hours and then fixed. Immunofluorescence was carried out as described in the Materials and Methods for p65 (green) and DAPI (blue). Representative pictures (400×) are shown. Arrows indicate cells with p65 nuclear translocation. F-actin / Vimentin / E-cadherin ; PubMed: 27580057 Oncotarget Immunofluorescence microscopy analysis of rhodamine phalloidin-stained F-actin, DAPI-stained nuclei, vimentin and E-cadherin in the cells.	24763611 27580057
Growth inhibition assay	GI50; PubMed: 29573334 Mol Oncol Screening of in vitro sensitivity to regorafenib in 14 gastric and 10 colorectal cancer cell lines. MTT cell proliferation assays were performed with increasing concentrations of regorafenib for 72 h. GI 50 values were averaged from at least three independent experiments in hexaplicate. Cell viability; PubMed: 25071018 Oncotarget MTT assay was performed to measure the cell viability in the colon cancer cell lines 2 days after treatment with regorafenib in a dose-dependent manner.	29573334 25071018

In vivo

Regorafenib reveals potent dose-dependent TGI in various preclinical human xenograft models in mice, with tumor shrinkages in breast MDA-MB-231 and renal 786-O carcinoma models. Regorafenib prevents not only the growth of syngeneic primary 4T1 breast tumors growing orthotopically in the fat pad, but also suppresses the formation of tumor metastasis in the lung. ^[1]

Protocol

Kinase Assay:^[1]	- Collapse Kinase assays: In vitro assays using recombinant VEGFR2 (murine aa785–aa1367), VEGFR3 (murine aa818–aa1363), PDGFRβ (aa561–aa1106), Raf-1 (aa305–aa648) and BRafV600E (aa409–aa765) kinase domains are performed. Initial in vitro kinase inhibition profiling is performed at a fixed 1 μM Regorafenib concentration. Inhibitory concentration of 50% (IC50) values are determined from selected responding kinases, e.g., VEGFR1 and RET. TIE2 kinase inhibition is measured with a homogeneous time-resolved fluorescence (HTRF) assay using a recombinant fusion protein of glutathione-S-transferase, the intracellular domain of TIE2 and the peptide biotin-Ahx-EPKDDAYPLYSDFG as substrate.
Cell Research:^[1]	- Collapse Cell lines: GIST 882 and TT cells Concentrations: 5 nM-10 μM Incubation Time: 96 hours Method: For proliferation assays, GIST 882 and TT cells are grown in RPMI medium containing L-glutamine, and MDA-MB-231, HepG2 and A375 cells in DMEM always containing 10% hiFBS. Cells are 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 10 μM and 5 nM final concentrations, and 0.2% DMSO, is added and incubation is continued for 96 hours. Cell proliferation is quantified. (Only for Reference)
Animal Research:^[1]	- Collapse Animal Models: Female athymic NCr nu/nu mice with Colo-205, MDA-MB-231 or 786-O Dosages: 3 mg/kg, 10 mg/kg, 30 mg/kg, 100 mg/kg Administration: Orally (Only for Reference)

References

Solubility (25°C)

In vitro	DMSO	97 mg/mL (200.9 mM)
	Water	Insoluble
	Ethanol	Insoluble
In vivo	Add solvents to the product individually and in order(Data is from Selleck tests instead of citations): 2% DMSO+30% PEG 300+5% Tween 80+ddH2O For best results, use promptly after mixing.	5mg/mL

* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

Chemical Information Download Regorafenib (BAY 73-4506) SDF

Molecular Weight	482.82
Formula	C₂₁H₁₅ClF₄N₄O₃
CAS No.	755037-03-7
Storage	3 years-20°C powder 2 years-80°C in solvent
Synonyms	Fluoro-Sorafenib, Resihance, Stivarga
Smiles	CNC(=O)C1=NC=CC(=C1)OC2=CC(=C(C=C2)NC(=O)NC3=CC(=C(C=C3)Cl)C(F)(F)F)F

In vivo Formulation Calculator (Clear solution)

Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)

Dosage

mg/kg

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Step 2: Enter the in vivo formulation (Different batches have different solubility ratios, please contact Selleck to provide you with the correct ratio)

% DMSO+ % + % Tween 80+ % ddH₂O

Calculate Reset

Calculation results:

Working concentration： mg/ml；

Method for preparing DMSO master liquid: ： mg drug pre-dissolved in μL DMSO (Master liquid concentration mg/mL， Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )

Method for preparing in vivo formulation：Take DMSO master liquid, next addμL PEG300， mix and clarify, next addμL Tween 80，mix and clarify, next add μL ddH₂O，mix and clarify.

Note：1.Please make sure the liquid is clear before adding the next solvent.
2.Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.

Bio Calculators

Molarity Calculator

Calculate the mass, volume or concentration required for a solution. The Selleck molarity calculator is based on the following equation:

Mass (mg) = Concentration (mM) × Volume (mL) × Molecular Weight (g/mol)

*When preparing stock solutions, please always use the batch-specific molecular weight of the product found on the via label and MSDS / COA (available on product pages).

Dilution Calculator

Calculate the dilution required to prepare a stock solution. The Selleck dilution calculator is based on the following equation:

Concentration _(start) x Volume _(start) = Concentration _(final) x Volume _(final)

This equation is commonly abbreviated as: C1V1 = C2V2 ( Input Output )

* When preparing stock solutions always use the batch-specific molecular weight of the product found on the vial label and MSDS / COA (available online).

The Serial Dilution Calculator Equation

Serial Dilutions
Concertration (start):
Dilution-folds:

Computed Result

C1=C0/X	C1:	LOG(C1):
C2=C1/X	C2:	LOG(C2):
C3=C2/X	C3:	LOG(C3):
C4=C3/X	C4:	LOG(C4):
C5=C4/X	C5:	LOG(C5):
C6=C5/X	C6:	LOG(C6):
C7=C6/X	C7:	LOG(C7):
C8=C7/X	C8:	LOG(C8):

Molecular Weight Calculator

Enter the chemical formula of a compound to calculate its molar mass and elemental composition:

Tip: Chemical formula is case sensitive. C10H16N2O2 c10h16n2o2

Instructions to calculate molar mass (molecular weight) of a chemical compound:

To calculate molar mass of a chemical compound, please enter its chemical formula and click 'Calculate'.

Definitions of molecular mass, molecular weight, molar mass and molar weight:

Molecular mass (molecular weight) is the mass of one molecule of a substance and is expressed in the unified atomic mass units (u). (1 u is equal to 1/12 the mass of one atom of carbon-12)
Molar mass (molar weight) is the mass of one mole of a substance and is expressed in g/mol.

Molarity Calculator

Clinical Trial Information (data from https://clinicaltrials.gov, updated on 2020-01-06)

NCT Number	Recruitment	interventions	Conditions	Sponsor/Collaborators	Start Date	Phases
NCT04476329	Recruiting	Drug: Regorafenib 40 MG	Hepatocellular Carcinoma	SC Liver Research Consortium LLC\|Bayer	December 15 2020	Phase 2
NCT04200404	Recruiting	Drug: CS1001\|Drug: Regorafenib	Advanced Refractory Solid Tumors	CStone Pharmaceuticals\|Bayer	December 13 2019	Phase 1\|Phase 2
NCT03793361	Recruiting	Drug: Regorafenib\|Drug: Placebo	Metastatic Soft Tissue Sarcoma	Centre Oscar Lambret	May 15 2019	Phase 2
NCT03829852	Recruiting	Drug: Regorafenib	Metastatic Colorectal Cancer	Taipei Veterans General Hospital Taiwan\|Chang Gung Memorial Hospital\|Koo Foundation Sun Yat-Sen Cancer Center	March 29 2019	--

Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

Tel: +1-832-582-8158 Ext:3

If you have any other enquiries, please leave a message.

Frequently Asked Questions

Question 1:
How to resuspend Regorafenib for in vivo studies?
Answer:
For in vivo study, we recommend to use 2% DMSO+30% PEG 300+5% Tween 80+ddH2O up to 5mg/ml.

VEGFR Signaling Pathway Map

VEGFR Inhibitors with Unique Features

Selective VEGFR Inhibitors

Vandetanib (ZD6474) : VEGFR2-selective, IC50=40 nM.
Most Potent VEGFR Inhibitor

Cabozantinib (XL184, BMS-907351) : VEGFR2, IC50=0.035 nM.
FDA-approved VEGFR Inhibitor

Axitinib : Approved by FDA for Renal Cell Carcinoma.
Classic VEGFR Inhibitor

Nintedanib (BIBF 1120) : Potent triple angiokinase inhibitor for VEGFR1/2/3, FGFR1/2/3 and PDGFRα/β with IC50 of 34 nM/13 nM/13 nM, 69 nM/37 nM/108 nM and 59 nM/65 nM. Phase 3.

Related VEGFR Products

SU5402 ^New

SU5402 is a potent multi-targeted receptor tyrosine kinase inhibitor with IC50 of 20 nM, 30 nM, and 510 nM for VEGFR2, FGFR1, and PDGF-Rβ, respectively.
Erlotinib ^New

Erlotinib (CP358774, NSC 718781) is an EGFR inhibitor with IC50 of 2 nM, >1000-fold more sensitive for EGFR than human c-Src or v-Abl. Erlotinib induces autophagy.
Bemcentinib (R428) ^New

Bemcentinib (R428, BGB324) is an inhibitor of Axl with IC50 of 14 nM, >100-fold selective for Axl versus Abl. Selectivty for Axl is also greater than Mer and Tyro3 (50-to-100- fold more selective) and InsR, EGFR, HER2, and PDGFRβ (100- fold more selective).
Axitinib

Axitinib (AG 013736) is a multi-target inhibitor of VEGFR1, VEGFR2, VEGFR3, PDGFRβ and c-Kit with IC50 of 0.1 nM, 0.2 nM, 0.1-0.3 nM, 1.6 nM and 1.7 nM in Porcine aorta endothelial cells, respectively.

Features:Superior as second-line therapy relative to sorafenib (current standard-of-care).
Cabozantinib (BMS-907351)

Cabozantinib (XL184, BMS-907351) is a potent VEGFR2 inhibitor with IC50 of 0.035 nM and also inhibits c-Met, Ret, Kit, Flt-1/3/4, Tie2, and AXL with IC50 of 1.3 nM, 4 nM, 4.6 nM, 12 nM/11.3 nM/6 nM, 14.3 nM and 7 nM in cell-free assays, respectively. Cabozantinib induces PUMA-dependent apoptosis in colon cancer cells via AKT/GSK-3β/NF-κB signaling pathway.
Nintedanib (BIBF 1120)

Nintedanib (BIBF 1120, Intedanib, Vargatef, Ofev) is a potent triple angiokinase inhibitor for VEGFR1/2/3, FGFR1/2/3 and PDGFRα/β with IC50 of 34 nM/13 nM/13 nM, 69 nM/37 nM/108 nM and 59 nM/65 nM in cell-free assays. Phase 3.
Vandetanib (ZD6474)

Vandetanib (ZD6474) is a potent inhibitor of VEGFR2 with IC50 of 40 nM in a cell-free assay. It also inhibits VEGFR3 and EGFR with IC50 of 110 nM and 500 nM, respectively. Not sensitive to PDGFRβ, Flt1, Tie-2 and FGFR1 with IC50 of 1.1-3.6 μM. No activity against MEK, CDK2, c-Kit, erbB2, FAK, PDK1, Akt and IGF-1R with IC50 above 10 μM. Vandetanib (ZD6474) increases apoptosis and induces autophagy by increasing the level of reactive oxygen species (ROS).
Lenvatinib (E7080)

Lenvatinib (E7080) is a multi-target inhibitor, mostly for VEGFR2(KDR)/VEGFR3(Flt-4) with IC50 of 4 nM/5.2 nM, less potent against VEGFR1/Flt-1, ~10-fold more selective for VEGFR2/3 against FGFR1, PDGFRα/β in cell-free assays. Lenvatinib (E7080) also inhibits FGFR1-4, PDGFR, Kit (c-Kit), RET (c-RET), and shows potent antitumor activities. Phase 3.
Pazopanib

Pazopanib (GW786034) is a novel multi-target inhibitor of VEGFR1, VEGFR2, VEGFR3, PDGFR, FGFR, c-Kit and c-Fms/CSF1R with IC50 of 10 nM, 30 nM, 47 nM, 84 nM, 74 nM, 140 nM and 146 nM in cell-free assays, respectively. Pazopanib induces cathepsin B activation and autophagy.
Pazopanib HCl (GW786034 HCl)

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. Pazopanib induces autophagic Type II cell death.

Features:A multi-kinase inhibitor.

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Regorafenib (BAY 73-4506)