Regorafenib (BAY 73-4506)

Name: Regorafenib (BAY 73-4506)
Brand: Selleck Chemicals
SKU: S1178
Rating: 5 (145 reviews)

For research use only.

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

145 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 145 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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Neoplasia, 2021, 23(3):304-325

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Mol Cancer Res, 2021, molcanres.0808.2020

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Cancer Immunol Immunother, 2021, 70(1):203-213

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Front Pharmacol, 2021, 12:632201

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J Gastroenterol Hepatol, 2021, 10.1111/jgh.15619

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Molecules, 2021, 26(16)4949

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PLoS One, 2021, 16(7):e0253258

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PLoS One, 2021, 16(7):e0252689

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Hum Cell, 2021, 10.1007/s13577-021-00579-z

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Int J Mol Sci, 2021, 22(3)1502

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Journal of Cancer, 2021, 12(21): 6356-6362

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Food Funct, 2021, 10.1039/d0fo02270e

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Commun Biol, 2021, 4(1):1067

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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

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

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EBioMedicine, 2019, 41:175-184

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

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Cancers (Basel), 2019, 11(4)

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

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

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

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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)

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BMC Microbiol, 2019, 19(1):34

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Dis Markers, 2019, 2019:8964015

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

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

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

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

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

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

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

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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

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

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

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

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Oncotarget, 2018, 9(56):30869-30882

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

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

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

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

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

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Clin Sci (Lond), 2017, 131(17):2275-2288

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

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

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

Sci Rep, 2017, 7(1):1502

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Molecules, 2017, 22(12)

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

PLoS One, 2017, 12(3):e0174151

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

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

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Med Sci Monit, 2017, 23:1963-1972

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J Mol Graph Model, 2017,

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

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

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

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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

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

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

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

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

PubMed: 27903966 ( click the link to review the publication )

Oncotarget, 2017, 9(17):13154-13166

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

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

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

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

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Oncotarget, 2017,

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

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

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

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

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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

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

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

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Sci Rep, 2016, 6:35308

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

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

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

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

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

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

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

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

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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(30):28929-37

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

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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	NXGyUIw{SXCxcITvd4l{KEG\|c3H5	MlfHNgKBmzYEoN88US=>	MYS0PEBp		M{PENYlvcGmkaYTzJINmdGxiZ4Lve5Rp	M2\QOFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ4M{K5OlA5Lz5{NkOyPVYxQDxxYU6=
PLC/PRF/5	NEftdndCeG:ydH;zbZMhSXO\|YYm=	NIHpOo4y6oDVNdMg{txO	NH3VNJA1QCCq		MlK2bY5pcWKrdIOgZ4VtdCCpcn;3eIg>	NVm1WFYyRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMk[zNlk3ODhpPkK2N\|I6PjB6PD;hQi=>
HepG2	MWrBdI9xfG:\|aYOgRZN{[Xl?	MojWNgKBmzYEoN88US=>	M3yzblQ5KGh?		MonYbY5pcWKrdIOgZ4VtdCCpcn;3eIg>	MUC8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPjN{OU[wPEc,OjZ\|Mkm2NFg9N2F-
HEK293	Mn7YSpVv[3Srb36gRZN{[Xl?	MnXXNE426oDLzszN	NVLlZ\|Y3Oi92L{[gbC=>		M2XuZZJm\HWlZYOgS3JRPzhiZYjwdoV{e2mxbh?=	NYO2cZE5RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkW4OVgxOzJpPkK1PFU5ODN{PD;hQi=>
GEO	MkXjS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?	NIrKR2IxNjBzLUKwJO69VQ>?	MXG5OkBp	NGjNbYJFVVOR	NEDPc2NqdmirYnn0d{Bk\WyuIHfyc5d1cCCrbjDhJIRwe2VvZHXw[Y5l\W62IH3hco5meg>?	M2fVXlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ3OEO4N\|kyLz5{NUizPFM6OTxxYU6=
SW48	NGHBZWhIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=	NHLXW4YxNjBzLUKwJO69VQ>?	Ml7iPVYhcA>?	NFezTolFVVOR	MljsbY5pcWKrdIOgZ4VtdCCpcn;3eIghcW5iYTDkc5NmNWSncHXu[IVvfCCvYX7u[ZI>	MlXMQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjV6M{izPVEoRjJ3OEO4N\|kyRC:jPh?=
HT29	Ml7US5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?	NUn2SZhtOC5yMT2yNEDPxE1?	M1;GV\|k3KGh?	MUPEUXNQ	NWfKRmNtcW6qaXLpeJMh[2WubDDndo94fGhiaX6gZUBld3OnLXTldIVv\GWwdDDtZY5v\XJ?	NXTxT\|VTRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkW4N\|g{QTFpPkK1PFM5OzlzPD;hQi=>
SW480	NFHudlFIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=	MX6wMlAyNTJyIN88US=>	M3;JVVk3KGh?	MWrEUXNQ	M3zsZYlvcGmkaYTzJINmdGxiZ4Lve5RpKGmwIHGg[I9{\S2mZYDlcoRmdnRibXHucoVz	NFnQPG89[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NUizPFM6OSd-MkW4N\|g{QTF:L3G+
SW620	M2L3R2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7	M4W5XFAvODFvMkCg{txO	NFrlVGE6PiCq	MonXSG1UVw>?	NIi1WItqdmirYnn0d{Bk\WyuIHfyc5d1cCCrbjDhJIRwe2VvZHXw[Y5l\W62IH3hco5meg>?	NVvLOohtRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkW4N\|g{QTFpPkK1PFM5OzlzPD;hQi=>
HCT116	MYTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?	NXr2e\|JJOC5yMT2yNEDPxE1?	NVj0TZJlQTZiaB?=	M1nO[GROW09?	MmTDbY5pcWKrdIOgZ4VtdCCpcn;3eIghcW5iYTDkc5NmNWSncHXu[IVvfCCvYX7u[ZI>	M3XDUVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ3OEO4N\|kyLz5{NUizPFM6OTxxYU6=
LOVO	NUH5[FZyT3Kxd4ToJGlvcGmkaYTpc44hSXO\|YYm=	NV:yT\|ZzOC5yMT2yNEDPxE1?	NV7HTJliQTZiaB?=	NVjPcZc3TE2VTx?=	M{DiNYlvcGmkaYTzJINmdGxiZ4Lve5RpKGmwIHGg[I9{\S2mZYDlcoRmdnRibXHucoVz	NVzoTYRnRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkW4N\|g{QTFpPkK1PFM5OzlzPD;hQi=>
HCT150	M2fCWWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7	NGX1NpAxNjBzLUKwJO69VQ>?	M1npNlk3KGh?	M1TVXGROW09?	MXXpcohq[mm2czDj[YxtKGe{b4f0bEBqdiCjIHTvd4Uu\GWyZX7k[Y51KG2jbn7ldi=>	MofPQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjV6M{izPVEoRjJ3OEO4N\|kyRC:jPh?=
SW48-CR	MYDHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?	NFrDdIQxNjBzLUKwJO69VQ>?	MmrtPVYhcA>?	NIe1WIFFVVOR	MknRbY5pcWKrdIOgZ4VtdCCpcn;3eIghcW5iYTDkc5NmNWSncHXu[IVvfCCvYX7u[ZI>	M3;pTlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ3OEO4N\|kyLz5{NUizPFM6OTxxYU6=
GEO-CR	MUnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?	M4HvXlAvODFvMkCg{txO	MnnVPVYhcA>?	NH7DfGJFVVOR	NGrvb21qdmirYnn0d{Bk\WyuIHfyc5d1cCCrbjDhJIRwe2VvZHXw[Y5l\W62IH3hco5meg>?	NVvGNoFmRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkW4N\|g{QTFpPkK1PFM5OzlzPD;hQi=>
KB-31	NHvjdYVIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=				MVvJR\|UxRTVwNdMxNE4{KG6P	M2fOOlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ3N{WzN\|YyLz5{NUe1N\|M3OTxxYU6=
KB-G2	MWDHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?				NEe3TllKSzVyPUmuNeKyOC5zIH7N	M4rwc\|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ3N{WzN\|YyLz5{NUe1N\|M3OTxxYU6=
LLC-PK1	MX3Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?				NGHpcpBKSzVyPUSyMlDDuTNwMjDuUS=>	NXvkV3h{RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkW3OVM{PjFpPkK1O\|U{OzZzPD;hQi=>
LLC-PK1/MRP2	MnzwS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?				NF;WbI5KSzVyPUiyMlTDuTJwNzDuUS=>	MoWxQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjV5NUOzOlEoRjJ3N{WzN\|YyRC:jPh?=
HEK293	Ml;pS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?				M1Hsd2lEPTB;MUGuNOKyOS5{IH7N	NHrad4w9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NUe1N\|M3OSd-MkW3OVM{PjF:L3G+
HEK293/OATP1B1	MnnSS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?				M2\Sc2lEPTB;Nj6yxtExNjNibl2=	Mlf5QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjV5NUOzOlEoRjJ3N{WzN\|YyRC:jPh?=
HROC18	MljUS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?				NHfhc2lKSzVyPUGuN{DPxE1?	MmPlQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjV\|MEm5NVQoRjJ3M{C5PVE1RC:jPh?=
HROC24	NXz3W4lXT3Kxd4ToJGlvcGmkaYTpc44hSXO\|YYm=				NUf6VGRGUUN3ME20MlYh\|ryP	MUG8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPTNyOUmxOEc,OjV\|MEm5NVQ9N2F-
HROC43	MkTqS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?				NYXCeIZIUUN3ME21MlMh\|ryP	NGS1NGU9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NUOwPVkyPCd-MkWzNFk6OTR:L3G+
HROC46	MYjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?				M2Lmd2lEPTB;Mj60JO69VQ>?	M4nNU\|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ3M{C5PVE1Lz5{NUOwPVkyPDxxYU6=
RJ345	MV7GeY5kfGmxbjDBd5NigQ>?	M1LRe\|AvPS93IN88US=>	M{nlTVI1KGh?	MU\EUXNQ	NFXGPZFqdmirYnn0d{B1cGViY3XscEBucWe{YYTpc44>	MkTrQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjV{NUO5PVQoRjJ3MkWzPVk1RC:jPh?=
RJ348	MnXRSpVv[3Srb36gRZN{[Xl?	NYP1SYRwOC53L{Wg{txO	NGfn[XozPCCq	MkjySG1UVw>?	MYLpcohq[mm2czD0bIUh[2WubDDtbYdz[XSrb36=	NX\sdFQyRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkWyOVM6QTRpPkK1NlU{QTl2PD;hQi=>
MCF-7	MnXUSpVv[3Srb36gRZN{[Xl?	M{C3OlAvPS93IN88US=>	M3HF[FI1KGh?	NHnkcZRFVVOR	NUC0VIlEcW6qaXLpeJMhfGinIHPlcIwhdWmpcnH0bY9v	NELHfYw9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NUK1N\|k6PCd-MkWyOVM6QTR:L3G+
MDA-MB-231	M1u1UWZ2dmO2aX;uJGF{e2G7	NHX0fnkxNjVxNTFOwG0>	NFe1c2MzPCCq	MVHEUXNQ	NY\BdJQ3cW6qaXLpeJMhfGinIHPlcIwhdWmpcnH0bY9v	M{XWTVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ3MkWzPVk1Lz5{NUK1N\|k6PDxxYU6=
HT15	MonIS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?	NVHvSJVKOS1{MDFOwG0>	NEfSSow1QCCq		MkfUbY5pcWKrdIOgZ4VtdCCpcn;3eIghcW5iYTDkc5NmNWSncHXu[IVvfCCvYX7u[ZI>	M3TmUVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ3MEexNFE5Lz5{NUC3NVAyQDxxYU6=
DLD1	MVLHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?	MWOxMVIxKM7:TR?=	Mlm1OFghcA>?		M1nze4lvcGmkaYTzJINmdGxiZ4Lve5RpKGmwIHGg[I9{\S2mZYDlcoRmdnRibXHucoVz	MVK8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPTB5MUCxPEc,OjVyN{GwNVg9N2F-
HT-29	Mn7CS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?	MlzHNU0zOCEQvF2=	NGnLT\|U1QCCq		M4m5NolvcGmkaYTzJINmdGxiZ4Lve5RpKGmwIHGg[I9{\S2mZYDlcoRmdnRibXHucoVz	M{PpZ\|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ3MEexNFE5Lz5{NUC3NVAyQDxxYU6=
Hct-116	MkjBS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?	MlHxNU0zOCEQvF2=	NHX1XZQ1QCCq		MV;pcohq[mm2czDj[YxtKGe{b4f0bEBqdiCjIHTvd4Uu\GWyZX7k[Y51KG2jbn7ldi=>	NW\ib405RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkWwO\|ExOThpPkK1NFcyODF6PD;hQi=>
HT15	Mm[3RZBweHSxc3nzJGF{e2G7	Mk\pNU0yOCEQvF2=	MYG0PEBp		MoPWbY5lfWOnczDj[YxtKGSnYYToJIlvKGFiZH;z[U1l\XCnbnTlcpQhdWGwbnXy	NHHsdnk9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NUC3NVAyQCd-MkWwO\|ExOTh:L3G+
DLD1	NX\ZSnVFSXCxcITvd4l{KEG\|c3H5	M{HmVFEuOTBizszN	NWrJeoFzPDhiaB?=		MVTpcoR2[2W\|IHPlcIwh\GWjdHigbY4h[SCmb4PlMYRmeGWwZHXueEBu[W6wZYK=	NEC2OVY9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NUC3NVAyQCd-MkWwO\|ExOTh:L3G+
HT-29	NGi2eXpCeG:ydH;zbZMhSXO\|YYm=	MXOxMVExKM7:TR?=	NGfkblY1QCCq		MUnpcoR2[2W\|IHPlcIwh\GWjdHigbY4h[SCmb4PlMYRmeGWwZHXueEBu[W6wZYK=	NUmycnBXRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkWwO\|ExOThpPkK1NFcyODF6PD;hQi=>
Hct-116	MlrYRZBweHSxc3nzJGF{e2G7	M4\reFEuOTBizszN	MVq0PEBp		NHrGOJZqdmS3Y3XzJINmdGxiZHXheIghcW5iYTDkc5NmNWSncHXu[IVvfCCvYX7u[ZI>	MXK8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPTB5MUCxPEc,OjVyN{GwNVg9N2F-
GBM5	NGO0WVZCeG:ydH;zbZMhSXO\|YYm=	MofmNE426oDVMT6w5qCK\|ryP	NELTbGczPCCq	MoXYSG1UVw>?	NFXpT5lqdnSncnHjeJMhf2m2aDDsZZBifGmwaXKgeI8hcW6mdXPlJINmdGxiZHXheIg>	M2PLbFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ2OUGxNlE2Lz5{NEmxNVIyPTxxYU6=
GBM6	NVjTdlNVSXCxcITvd4l{KEG\|c3H5	M17JdVAvPeLCk{GuNQKBkc7:TR?=	NGHHR3YzPCCq	M4HsO2ROW09?	NEPuVm5qdnSncnHjeJMhf2m2aDDsZZBifGmwaXKgeI8hcW6mdXPlJINmdGxiZHXheIg>	MXK8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPDlzMUKxOUc,OjR7MUGyNVU9N2F-
GBM12	MX\BdI9xfG:\|aYOgRZN{[Xl?	NYTnWYx2OC534pETNU4x6oDLzszN	NETTNZUzPCCq	M1zqXWROW09?	NYrS[GM1cW62ZYLhZ5R{KHerdHigcIFx[XSrbnniJJRwKGmwZIXj[UBk\WyuIHTlZZRp	M{L3V\|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ2OUGxNlE2Lz5{NEmxNVIyPTxxYU6=
GBM14	M4myVGFxd3C2b4Ppd{BCe3OjeR?=	NGHzfmUxNjYkgKOxMlDjiIoQvF2=	MUeyOEBp	NVS1PJNmTE2VTx?=	NHvzWoRqdnSncnHjeJMhf2m2aDDsZZBifGmwaXKgeI8hcW6mdXPlJINmdGxiZHXheIg>	NYTXUYlPRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkS5NVEzOTVpPkK0PVEyOjF3PD;hQi=>
Hep3B	MXzHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?	MYmx5qCUOi53wrFOwG0>	MlHHNlQwPDhxN{KgbC=>		NGr1WpBqdmirYnn0d{Bk\WyuIHfyc5d1cA>?	NVK4elNwRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkS4PFU5QTBpPkK0PFg2QDlyPD;hQi=>
PLC/PRF/5	NUC2UJV7T3Kxd4ToJGlvcGmkaYTpc44hSXO\|YYm=	MVqx5qCUOi53wrFOwG0>	NV7KOJpDOjRxNEivO\|IhcA>?		MmnBbY5pcWKrdIOgZ4VtdCCpcn;3eIg>	MlzGQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjR6OEW4PVAoRjJ2OEi1PFkxRC:jPh?=
HepG2	MUTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?	NVjScohqOeLCk{KuOeKh\|ryP	M3jV[lI1NzR6L{eyJIg>		NGLETYJqdmirYnn0d{Bk\WyuIHfyc5d1cA>?	M1ezXVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ2OEi1PFkxLz5{NEi4OVg6ODxxYU6=
HCT116	M3frbGZ2dmO2aX;uJGF{e2G7	Mk\2NVAwOjBxNECg{txO	NEnHUpAzPCCq		M1z0c4lv\HWlZYOgVHVOSSCycn;0[YlvKGGwZDDtVm5CKGW6cILld5Nqd25iaX6gZUBld3OnLTDhcoQhfGmvZT3k[ZBmdmSnboSgcYFvdmW{	NHvFeGY9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NEe2N\|YyOSd-MkS3OlM3OTF:L3G+
Lim2405	M2rNPWZ2dmO2aX;uJGF{e2G7	Mn3XOFAh\|ryP	M2q5SFI1KGh?		MXvpcoR2[2W\|IGDVUWEheHKxdHXpckBidmRiY3XscEBieG:ydH;zbZM>	NIXt[mM9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NEe2N\|YyOSd-MkS3OlM3OTF:L3G+
LoVo	MlvySpVv[3Srb36gRZN{[Xl?	Mn;uOFAh\|ryP	MmG4NlQhcA>?		NGLvS3NqdmS3Y3XzJHBWVUFicILveIVqdiCjbnSgZ4VtdCCjcH;weI9{cXN?	MVS8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPDd4M{[xNUc,OjR5NkO2NVE9N2F-
Lim1215	M{SwbGZ2dmO2aX;uJGF{e2G7	MVu0NEDPxE1?	NHH2SpEzPCCq		M1K1TYlv\HWlZYOgVHVOSSCycn;0[YlvKGGwZDDj[YxtKGGyb4D0c5Nqew>?	MlXWQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjR5NkO2NVEoRjJ2N{[zOlEyRC:jPh?=
SW48	M3jMWWZ2dmO2aX;uJGF{e2G7	Mn6yOFAh\|ryP	MkPoNlQhcA>?		NUPKR3hUcW6mdXPld{BRXU2DIIDyc5RmcW5iYX7kJINmdGxiYYDvdJRwe2m\|	Mn\JQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjR5NkO2NVEoRjJ2N{[zOlEyRC:jPh?=
RKO	NH7EO\|RHfW6ldHnvckBCe3OjeR?=	M13oOlQxKM7:TR?=	MWeyOEBp		MUnpcoR2[2W\|IGDVUWEheHKxdHXpckBidmRiY3XscEBieG:ydH;zbZM>	NED5d4I9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NEe2N\|YyOSd-MkS3OlM3OTF:L3G+
SW837	MXPGeY5kfGmxbjDBd5NigQ>?	M{PlOVQxKM7:TR?=	NHi3XlczPCCq		MkLUbY5lfWOnczDQWW1CKHC{b4TlbY4h[W6mIHPlcIwh[XCxcITvd4l{	M2e2bFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ2N{[zOlEyLz5{NEe2N\|YyOTxxYU6=
SW1463	M{O3fGZ2dmO2aX;uJGF{e2G7	MmflOFAh\|ryP	M2\SW\|I1KGh?		NWTRVZFCcW6mdXPld{BRXU2DIIDyc5RmcW5iYX7kJINmdGxiYYDvdJRwe2m\|	NIfsWnU9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NEe2N\|YyOSd-MkS3OlM3OTF:L3G+
SW480	MmGwSpVv[3Srb36gRZN{[Xl?	MXO0NEDPxE1?	NIf6RpczPCCq		NVvJW3lKcW6mdXPld{BRXU2DIIDyc5RmcW5iYX7kJINmdGxiYYDvdJRwe2m\|	NWHLSHQ{RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkS3OlM3OTFpPkK0O\|Y{PjFzPD;hQi=>
Vaco432	NVnpPJZ[TnWwY4Tpc44hSXO\|YYm=	NWDIbI5EPDBizszN	MmjJNlQhcA>?		M1Gz[Ilv\HWlZYOgVHVOSSCycn;0[YlvKGGwZDDj[YxtKGGyb4D0c5Nqew>?	M4jBPVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ2N{[zOlEyLz5{NEe2N\|YyOTxxYU6=
Vaco400	NEDkdoVHfW6ldHnvckBCe3OjeR?=	MW[0NEDPxE1?	M{nHO\|I1KGh?		MnnhbY5lfWOnczDQWW1CKHC{b4TlbY4h[W6mIHPlcIwh[XCxcITvd4l{	MYm8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPDd4M{[xNUc,OjR5NkO2NVE9N2F-
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BA/F3	MXHHdo94fGhiaX7obYJqfGmxbjDhd5NigQ>?		NFrzVlk4OiCqcoO=		M{f5SWlvcGmkaYTpc44hd2ZiS3n0JGQ5OT[YIH31eIFvfCBqdX7rco94diCxcnnnbY4qKHS{YX7z[oVkfGWmIHnuJI1wfXOnIFLBM2Y{KGOnbHzzJIF{e2W\|c3XkJIF{KGmwaHnibZRqd25ib3[gZ4VtdCCpcn;3eIghcW6ldXLheIVlKG[xcjC3NkBpenNiYomgUXRUKGG\|c3H5MEBIUTVyIE2gNk4{PzFizszNMi=>	M3fPe\|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzNyMkC0OFQyLz5\|MEKwOFQ1OTxxYU6=
GIST430	NU\kPFBuS3m2b4TvfIlkcXS7IHHzd4F6		M{W2WlczKGi{cx?=		MoDtR5l1d3SxeHnjbZR6KGGpYXnud5QhcHWvYX6gS2lUXDR\|MDDj[YxteyCqYYLic5JqdmdiS1nUJHY3PTSDIH31eIFvfCCjc4Pld5Nm\CCjczDj[YxtKGe{b4f0bEBqdmirYnn0bY9vKGGodHXyJFczKGi{czDifUBE\WyuVHn0[ZJIdG9iYYPzZZktKEeLNUCgQUA{KM7:TT6=	M{L5bFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ6OUmxOFY2Lz5{OEm5NVQ3PTxxYU6=
BA/F3	NEDyXVhEgXSxdH;4bYNqfHliYYPzZZk>		MoLEO\|IhcHK\|		NHvWVZhEgXSxdH;4bYNqfHliaX6gcY92e2VicHHy[Y51[WxiQlGvSlMh[2WubIOgbY5kfWKjdHXkJIZweiB5MjDodpMh[nliTWTTJIF{e2G7LDDHTVUxKD1iOT65OVMh\|ryPLh?=	NHTMbGs9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9\|MEKwOFQ1OSd-M{CyNFQ1PDF:L3G+
U-2 OS	MX\xTHRUKGG\|c3H5				MWDxTHRUKG:oIIDl[IlifHKrYzDjZY5k\XJiY3XscEBtcW6nczD0c{Bq\GWwdHnmfUBufWy2aYDs[UBweHCxcoT1col1cWW\|IH\vdkBlenWpIILldJVzeG:\|aX7nPkBRemmvYYL5JJNkemWnbjDmc5IhXS1{IF;TJINmdGy\|	NYL6RpNNRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkm0N\|UyOzlpPkK5OFM2OTN7PD;hQi=>
A673	NILOXoJyUFSVIHHzd4F6				NXXjdVVIeUiWUzDv[kBx\WSrYYTybYMh[2GwY3XyJINmdGxibHnu[ZMhfG9iaXTlcpRq\nlibYXseIlxdGVib4Dwc5J1fW6rdHnld{Bnd3JiZIL1[{Bz\XC3coDvd4lv\zpiUILpcYFzgSC\|Y4Ll[Y4h\m:{IFG2O\|Mh[2WubIO=	MYW8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTR\|NUGzPUc,Ojl2M{WxN\|k9N2F-
DAOY	Moi0dWhVWyCjc4PhfS=>				MUHxTHRUKG:oIIDl[IlifHKrYzDjZY5k\XJiY3XscEBtcW6nczD0c{Bq\GWwdHnmfUBufWy2aYDs[UBweHCxcoT1col1cWW\|IH\vdkBlenWpIILldJVzeG:\|aX7nPkBRemmvYYL5JJNkemWnbjDmc5IhTEGRWTDj[Yxtew>?	M4nndlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7NEO1NVM6Lz5{OUSzOVE{QTxxYU6=
Saos-2	NGLmN\|JyUFSVIHHzd4F6				M1LY[5FJXFNib3[gdIVlcWG2cnnjJINidmOncjDj[YxtKGyrbnXzJJRwKGmmZX70bYZ6KG23bITpdIxmKG:ycH;yeJVvcXSrZYOg[o9zKGS{dXegdoVxfXKyb4Ppcoc7KFC{aX3hdpkhe2O{ZXXuJIZweiCVYX;zMVIh[2WubIO=	NVrmbHh1RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkm0N\|UyOzlpPkK5OFM2OTN7PD;hQi=>
BT-37	MXPxTHRUKGG\|c3H5				MkX1dWhVWyCxZjDw[YRq[XS{aXOgZ4Fv[2W{IHPlcIwhdGmwZYOgeI8hcWSnboTp[pkhdXWudHnwcIUhd3Cyb4L0eY5qfGmnczDmc5Ih\HK3ZzDy[ZB2enCxc3nu[\|ohWHKrbXHyfUB{[3KnZX6g[o9zKEKWLUO3JINmdGy\|	M1vJWFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7NEO1NVM6Lz5{OUSzOVE{QTxxYU6=
RD	Mn7PdWhVWyCjc4PhfS=>				NX\afoRZeUiWUzDv[kBx\WSrYYTybYMh[2GwY3XyJINmdGxibHnu[ZMhfG9iaXTlcpRq\nlibYXseIlxdGVib4Dwc5J1fW6rdHnld{Bnd3JiZIL1[{Bz\XC3coDvd4lv\zpiUILpcYFzgSC\|Y4Ll[Y4h\m:{IGLEJINmdGy\|	Mke4QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjl2M{WxN\|koRjJ7NEO1NVM6RC:jPh?=
BT-12	NILZdIJyUFSVIHHzd4F6				M3nPN5FJXFNib3[gdIVlcWG2cnnjJINidmOncjDj[YxtKGyrbnXzJJRwKGmmZX70bYZ6KG23bITpdIxmKG:ycH;yeJVvcXSrZYOg[o9zKGS{dXegdoVxfXKyb4Ppcoc7KFC{aX3hdpkhe2O{ZXXuJIZweiCEVD2xNkBk\Wyucx?=	NHzFNFg9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUSzOVE{QSd-Mkm0N\|UyOzl:L3G+
MG 63 (6-TG R)	MU\xTHRUKGG\|c3H5				MXXxTHRUKG:oIIDl[IlifHKrYzDjZY5k\XJiY3XscEBtcW6nczD0c{Bq\GWwdHnmfUBufWy2aYDs[UBweHCxcoT1col1cWW\|IH\vdkBlenWpIILldJVzeG:\|aX7nPkBRemmvYYL5JJNkemWnbjDmc5IhVUdiNkOgLFYuXEdiUjmgZ4VtdHN?	MoP6QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjl2M{WxN\|koRjJ7NEO1NVM6RC:jPh?=
NB1643	NYPxc2NGeUiWUzDhd5NigQ>?				NEn3bWhyUFSVIH;mJJBm\GmjdILpZ{Bk[W6lZYKgZ4VtdCCuaX7ld{B1dyCrZHXueIlngSCvdXz0bZBt\SCxcIDvdpR2dmm2aXXzJIZweiCmcoXnJJJmeHW{cH;zbY5oQiCScnntZZJ6KHOlcnXlckBnd3JiTlKxOlQ{KGOnbHzz	NGrJUHg9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUSzOVE{QSd-Mkm0N\|UyOzl:L3G+
OHS-50	M3HSVJFJXFNiYYPzZZk>				NHK5VlVyUFSVIH;mJJBm\GmjdILpZ{Bk[W6lZYKgZ4VtdCCuaX7ld{B1dyCrZHXueIlngSCvdXz0bZBt\SCxcIDvdpR2dmm2aXXzJIZweiCmcoXnJJJmeHW{cH;zbY5oQiCScnntZZJ6KHOlcnXlckBnd3JiT1jTMVUxKGOnbHzz	NUf4[pkxRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkm0N\|UyOzlpPkK5OFM2OTN7PD;hQi=>
SJ-GBM2	MknKdWhVWyCjc4PhfS=>				M{e4WJFJXFNib3[gdIVlcWG2cnnjJINidmOncjDj[YxtKGyrbnXzJJRwKGmmZX70bYZ6KG23bITpdIxmKG:ycH;yeJVvcXSrZYOg[o9zKGS{dXegdoVxfXKyb4Ppcoc7KFC{aX3hdpkhe2O{ZXXuJIZweiCVSj3HRm0zKGOnbHzz	M17DSVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7NEO1NVM6Lz5{OUSzOVE{QTxxYU6=
SK-N-MC	NWfTTJB{eUiWUzDhd5NigQ>?				MWfxTHRUKG:oIIDl[IlifHKrYzDjZY5k\XJiY3XscEBtcW6nczD0c{Bq\GWwdHnmfUBufWy2aYDs[UBweHCxcoT1col1cWW\|IH\vdkBlenWpIILldJVzeG:\|aX7nPkBRemmvYYL5JJNkemWnbjDmc5IhW0tvTj3NR{Bk\Wyucx?=	NEP3PII9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUSzOVE{QSd-Mkm0N\|UyOzl:L3G+
NB-EBc1	MkXOdWhVWyCjc4PhfS=>				MmDtdWhVWyCxZjDw[YRq[XS{aXOgZ4Fv[2W{IHPlcIwhdGmwZYOgeI8hcWSnboTp[pkhdXWudHnwcIUhd3Cyb4L0eY5qfGmnczDmc5Ih\HK3ZzDy[ZB2enCxc3nu[\|ohWHKrbXHyfUB{[3KnZX6g[o9zKE6ELVXCZ\|Eh[2WubIO=	MVW8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTR\|NUGzPUc,Ojl2M{WxN\|k9N2F-
LAN-5	MomwdWhVWyCjc4PhfS=>				NXr6UGVoeUiWUzDv[kBx\WSrYYTybYMh[2GwY3XyJINmdGxibHnu[ZMhfG9iaXTlcpRq\nlibYXseIlxdGVib4Dwc5J1fW6rdHnld{Bnd3JiZIL1[{Bz\XC3coDvd4lv\zpiUILpcYFzgSC\|Y4Ll[Y4h\m:{IFzBUk02KGOnbHzz	NEHLcXo9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUSzOVE{QSd-Mkm0N\|UyOzl:L3G+
Rh18	MVjxTHRUKGG\|c3H5				MWfxTHRUKG:oIIDl[IlifHKrYzDjZY5k\XJiY3XscEBtcW6nczD0c{Bq\GWwdHnmfUBufWy2aYDs[UBweHCxcoT1col1cWW\|IH\vdkBlenWpIILldJVzeG:\|aX7nPkBRemmvYYL5JJNkemWnbjDmc5IhWmhzODDj[Yxtew>?	M4S3XVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7NEO1NVM6Lz5{OUSzOVE{QTxxYU6=

... 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 (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)

% DMSO+ % + % Tween 80+ % ddH₂O

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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 μL 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 SDS / 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 SDS / 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 2021-09-06)

NCT Number	Recruitment	interventions	Conditions	Sponsor/Collaborators	Start Date	Phases
NCT05023720	Recruiting	Other: nonintervention	Metastatic Colorectal Cancer	Henan Cancer Hospital	July 20 2021	--
NCT04920422	Active not recruiting	Other: No intervention	Metastatic Colorectal Cancer	Bayer	July 15 2021	--
NCT04476329	Recruiting	Drug: Regorafenib 40 MG	Hepatocellular Carcinoma	SC Liver Research Consortium LLC\|Bayer	January 21 2021	Phase 2
NCT04200404	Recruiting	Drug: CS1001\|Drug: Regorafenib	Advanced Refractory Solid Tumors	CStone Pharmaceuticals\|Bayer	December 13 2019	Phase 1\|Phase 2

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.

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Erlotinib (OSI-774) ^New

Erlotinib (OSI-774, CP358774, NSC 718781, Tarceva) 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 (AG 013736)

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)