<Suppliers Price>

Regorafenib

Names

[ CAS No. ]:
835621-08-4

[ Name ]:
Regorafenib

[Synonym ]:
4(4-[3-(4-chloro-3-trifluoromethylphenyl)-ureido]-3-fluorophenoxy)-pyridine-2-carboxylic acid methylamide mesylate
Regorafenib

Biological Activity

[Description]:

Regorafenib (BAY 73-4506) mesylate is an orally active and potent multi-targeted receptor tyrosine kinase inhibitor, with IC50 values of 13/4.2/46, 22, 7, 1.5 and 2.5 nM for VEGFR1/2/3, PDGFRβ, Kit, RET and Raf-1, respectively. Regorafenib mesylate shows very robust antitumor and antiangiogenic activity[1].

[Related Catalog]:

Research Areas >> Cancer
Signaling Pathways >> Protein Tyrosine Kinase/RTK >> PDGFR
Signaling Pathways >> Protein Tyrosine Kinase/RTK >> FGFR
Signaling Pathways >> Autophagy >> Autophagy
Signaling Pathways >> MAPK/ERK Pathway >> Raf
Signaling Pathways >> Protein Tyrosine Kinase/RTK >> VEGFR
Signaling Pathways >> Protein Tyrosine Kinase/RTK >> c-Kit

[Target]

Raf-1:2.5 ± 0.6 nM (IC50)

VEGFR2:4.2 ± 1.6 nM (IC50)

VEGFR1:13 ± 0.4 nM (IC50)

BRafV600E:19 ± 6 nM (IC50)

PDGFRβ:22 ± 3 nM (IC50)

B-Raf:28 ± 10 nM (IC50)

VEGFR3:46 ± 10 nM (IC50)


[In Vitro]

Regorafenib mesylate (0-10 μM, 96 h) shows anti-proliferation activity in GIST 882, Thyroid TT, MDA-MB-231, HepG2, A375 and SW620 cells[1]. Regorafenib mesylate (0-3000 nM, 30 min) inhibits the autophosphorylation of VEGFR2, TIE2 and PDGFR-β, and inhibits FGFR and pERK1/2[1]. Regorafenib mesylate causes a concentration-dependent decrease in Hep3B cell growth, with an IC50 of 5 μM. Regorafenib subsequently increases the levels of phospho-c-Jun, a JNK target, but not total c-Jun in Hep3B cells[2]. Cell Proliferation Assay[1] Cell Line: GIST 882, Thyroid TT, MDA-MB-231, HepG2, A375 and SW620 cells Concentration: 10 μM and 5 nM Incubation Time: 96 h Result: Showed anti-proliferation activity in GIST 882, Thyroid TT, MDA-MB-231, HepG2, A375 and SW620 cells, with IC50 values of 45 ± 20, 34 ± 8, 401 ± 88, 560 ± 200, 900, 967 ± 287 nM. respectively. Western Blot Analysis[1] Cell Line: NIH-3T3/VEGFR2 cells, (CHO)-TIE2 cells, HAoSMCs cells, MCF-7 cells Concentration: 0, 10, 30, 100, 300, 1000, 3000 nM Incubation Time: 30 min Result: Inhibited the autophosphorylation of VEGFR2, TIE2 and PDGFR-β, with IC50 values of 3, 31, and 90 nM, respectively, inhibited FGFR signaling in MCF-7 breast cancer (BC) cells stimulated with FGF10, and showed inhibition of phosphorylated FGFR substrate 2 (pFRS2) and the downstream signaling kinase pERK1/2.

[In Vivo]

Regorafenib mesylate (10 mg/kg, Orally, single dose or daily for 4 days) inhibits tumor vasculature and tumor growth in a rat GS9L glioblastoma model[1]. Regorafenib mesylate (0-100 mg/kg, Orally, qd × 9) exhibits antitumorigenic and antiangiogenic effects in the Colo-205, MDA-MB-231 and 786-O model[1]. Animal Model: Rat GS9L glioblastoma xenograft[1] Dosage: 10 mg/kg Administration: Orally, single dose or daily for 4 days Result: Inhibited tumor vasculature and tumor growth in a rat GS9L glioblastoma model. Animal Model: Female athymic NCr nu/nu mice, Multiple xenograft models, including models derived from CRC (Colo-205), BC (MDA-MB-231) and RCC (786-O) tumors[1] Dosage: 0, 3, 10, 30, 100 mg/kg Administration: Orally, qd × 9 Result: Effectively inhibited growth of the Colo-205, MDA-MB-231 and 786-O model. Significantly reduces tumor MVA, effectively inhibited the RAF/MEK/ERK signaling cascade, and drastically inhibited tumor cell proliferation.

[References]

[1]. Wilhelm SM, et al. Regorafenib (BAY 73-4506): a new oral multikinase inhibitor of angiogenic, stromal and oncogenic receptor tyrosine kinases with potent preclinical antitumor activity. Int J Cancer, 2011, 129(1), 245-255.

[2]. Carr BI, et al. Fluoro-Bay 43-9006 (Regorafenib) effects on hepatoma cells: growth inhibition, quiescence, and recovery. J Cell Physiol, 2013, 228(2), 292-297.

Chemical & Physical Properties

[ Molecular Formula ]:
C22H19ClF4N4O6S

[ Molecular Weight ]:
578.92100

[ Exact Mass ]:
578.06500

[ PSA ]:
155.10000

[ LogP ]:
6.81050


Related Compounds

The content on this webpage is sourced from various professional data sources. If you have any questions or concerns regarding the content, please feel free to contact service1@chemsrc.com.