Regorafenib

SKU: orb1224067

Description

A potent multikinase inhibitor that potently inhibits these endothelial cell kinases in biochemical and cellular kinase phosphorylation assays with nanomolar range (IC50=3-200 nM); inhibits VEGFR1/2/3, PDGFRβ, FGFR1, KIT, RET and B-RAF etc.; exhibits potent dose-dependent TGI in various preclinical human xenograft models in mice; orally active.Colon Cancer Approved(In Vitro):Regorafenib (0-10 μM, 96 h) shows anti-proliferation activity in GIST 882, Thyroid TT, MDA-MB-231, HepG2, A375 and SW620 cells.Regorafenib (0-3000 nM, 30 min) inhibits the autophosphorylation of VEGFR2, TIE2 and PDGFR-β, and inhibits FGFR and pERK1/2.Regorafenib 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.(In Vivo):Regorafenib (10 mg/kg, Orally, single dose or daily for 4 days) inhibits tumor vasculature and tumor growth in a rat GS9L glioblastoma model.Regorafenib (0-100 mg/kg, Orally, qd × 9) exhibits antitumorigenic and antiangiogenic effects in the Colo-205, MDA-MB-231 and 786-O model.

Research Area

Pharmacology & Drug Discovery

Key Properties

• CAS Number: 755037-03-7
• MW: 482.8154
• Purity: >98% (HPLC)
• Formula: C₂₁H₁₅ClF₄N₄O₃
• SMILES: C12=NC(NC3=CC=C(N4CCOCC4)C=C3)=NC(NC5CCCCC5)=C1NC=N2
• Target: VEGFR
• Solubility: DMSO: ≥ 260 mg/mL

Bioactivity

• In Vivo:
  Regorafenib (10 mg/kg, Orally, single dose or daily for 4 days) inhibits tumor vasculature and tumor growth in a rat GS9L glioblastoma model. Regorafenib (0-100 mg/kg, Orally, qd × 9) exhibits antitumorigenic and antiangiogenic effects in the Colo-205, MDA-MB-231 and 786-O model. Animal model: Rat GS9L glioblastoma xenograft. 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. 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.
• In Vitro:
  Regorafenib (0-10 μM, 96 h) shows anti-proliferation activity in GIST 882, Thyroid TT, MDA-MB-231, HepG2, A375 and SW620 cells. Regorafenib (0-3000 nM, 30 min) inhibits the autophosphorylation of VEGFR2, TIE2 and PDGFR-β, and inhibits FGFR and pERK1/2.Regorafenib 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. Cell Proliferation Assay 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. 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.

Storage & Handling

• Storage: Storage temperature: -20°C. Stability: ≥ 2 years
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

BAY 73-4506 | BAY73-4506

Quick Database Links

Gene Symbol

VEGFR