REVIEW Vargatef (also known as Nintedanib, BIBF 1120) is a indolinone-derived small molecule of angiokinase inhibitor class inhibiting vascular endothelial growth factor receptor (VEGFR), fibroblast growth factor receptor (FGFR) and platelet derived growth factor receptor (PDGFR) being developed by Boehringer Ingelheim for use as an anti-vascular anti-cancer agent. Nintedanib inhibits PDGFR kinase activity of PDGFR alpha and PDGFR beta types with IC50 values of 59 nM and 65 nM, respectively. In addition, BIBF1120 suppresses the FGFR subtypes with IC50 of 60 nM, 37 nM and 108 nM for FGFR1, FGFR2, and FGFR3, respectively. BIBF1120 binds to the ATP-binding site in the cleft between the amino and carboxy terminal lobes of the kinase domain. Vargatef inhibits the process of blood vessel formation (angiogenesis) in tumours. Angiogenesis inhibitors stop the formation and reshaping of blood vessels in and around tumours, which reduces the tumour's blood supply, starving tumour cells of oxygen and nutrients leading to cell death and tumour shrinkage. In all tumor models tested thus far, including human tumor xenografts growing in nude mice and a syngeneic rat tumor model, BIBF1120 is highly active at well-tolerated doses (25-100 mg/kg daily p.o.). This is evident in the magnetic resonance imaging of tumor perfusion after 3 days, reducing vessel density and vessel integrity after 5 days, and profound growth. The compound is currently in Phase 3 clinical trials.
REFERENCES
[1]
Kulimova, Emma; Oelmann, Elisabeth; Bisping, Guido; Kienast, Joachim; Mesters, Rolf M.; Schwaeble, Joachim; Hilberg, Frank; Roth, Gerald J.; Munzert, Gerd; Stefanic, Martin; Steffen, Bjoern; Brandts, Christian; Mueller-Tidow, Carsten; Kolkmeyer, Astrid; Buechner, Thomas; Serve, Hubert; Berdel, Wolfgang E. Growth inhibition and induction of apoptosis in acute myeloid leukemia cells by new indolinone derivatives targeting fibroblast growth factor, platelet-derived growth factor, and vascular endothelial growth factor receptors. Molecular Cancer Therapeutics (2006), 5(12), 3105-3112.
[2]
Hilberg F, Roth GJ, Krssak M, Kautschitsch S, Sommergruber W, Tontsch-Grunt U, Garin-Chesa P, Bader G, Zoephel A, Quant J, Heckel A, Rettig WJ. BIBF 1120: triple angiokinase inhibitor with sustained receptor blockade and good antitumor efficacy. Cancer Res. 2008 Jun 15;68(12):4774-82.
[3]
Okamoto I, Kaneda H, Satoh T, Okamoto W, Miyazaki M, Morinaga R, Ueda S, Terashima M, Tsuya A, Sarashina A, Konishi K, Arao T, Nishio K, Kaiser R, Nakagawa K. Phase I safety, pharmacokinetic, and biomarker study of BIBF 1120, an oral triple tyrosine kinase inhibitor in patients with advanced solid tumors. Mol Cancer Ther. 2010 Oct;9(10):2825-33.
[4]
Santos ES, Gomez JE, Raez LE. Targeting angiogenesis from multiple pathways simultaneously: BIBF 1120, an investigational novel triple angiokinase inhibitor. Invest New Drugs. 2012 Jun;30(3):1261-9.
All products are stocked and shipped from the SF Bay, California, USA via FedEx, UPS or DHL.
All batches backed with full quality assurance.
??
All products are for research and development use only, not for any other uses, and must be handled by technically-qualified persons.
These products are explicitly not intended to be used in foods and/or cosmetics and/or drugs (human and veterinary) and/or consumer products and/or biocides and/or pesticides of any kind unless explicitly stated otherwise.
Products are not sold to individuals. We do not ship to residential addresses. Consumer orders will be cancelled without notice.
New customers undergo an internal onboarding process. As part of this process, new customers may be asked for more information. Additional restrictions may apply.
Add to Favorites 
Delete from Favorites 
