Vascular endothelial growth factor inhibitor

Lucentis contains ranibizumab and is available for intravitreal injection. It is a vascular endothelial growth factor inhibitor indicated for the treatment of neovascular (wet) age-related macular degeneration. Unlike verteporfin, which is used in photodynamic treatment of age-related macular degeneration, ranibizumab does not require activation by local irradiation using non-thermal red light. 

Uses Neovascular wet macular degenoation Action Vascular endothelial growth factor inhibitor Dose 0.5 mg intravitreal inj qmo Caution [C ] Hx thromboembohsm Contra Periocular Infxn Disp Inj SE Endophthalmitis, retinal detachment/hemorrhage, cataract, intraocular inflammation, conjunctival hemorrhage, eye pain, floaters EMS None OD Unlikely, but immediate effect would be vision loss and pain d/t t ocular pressure... 

A fundamental process in biology is the proliferation of cells mediated by the cell cycle. On the basis of previous studies, Kuo et al. identified the pyrazino-pytidine compound 360 as a potent vascular endothelial growth factor inhibitor and the pyrimidino-pyridine species 361 as a moderately potent cyclin-dependent kinase (CDK) inhibitor (Figure 36). A proposed combination of CGP-60474 and compound 361 led to the discovery of the [l,3,5]triazino-pyridines 362 as a new series of potent CDK inhibitors <2005JME4535>. 

Small HY, Montezano AC, Rios FJ et al (2014) Hypertension due to antiangiogenic cancer therapy with vascular endothelial growth factor inhibitors understanding and managing a new syndrome. Can J Cardiol 30 534-543... 

Faruque LI, Lin M, Battistella M et al (2014) Systematic review of the risk of adverse outcomes associated with vascular endothelial growth factor inhibitors for the treatment of cancer. PLoS... 

Mintz-Hittner HA. Treatment of retinopathy of prematurity with vascular endothelial growth factor inhibitors. Early Hum Dev December 2012 88(12) 937-41. http //dx.doi.Org/10.1016/j.earlhumdev.2012.09.019. Epub 2012 October 15. PubMed PMID 23078830. 

Campbell RJ, GiU SS, BronskiU SE, Paterson JM, Whitehead M, Bell CM. Adverse events with intravitreal injection of vascular endothelial growth factor inhibitors nested case-control study. BMJ July 4, 2012 345 e4203. http //dx.doi.org/10.1136/bmj.e4203. PubMed PMID 22763393 PubMed Central PMOD PMC3389519. 

Optimization of the large (MW = 512), lipophilic (clogP = 7.6), and very potent (Kj = 0.22 nM) Vascular Endothelial Growth Factor Receptor Tyrosine Kinase (VEGFR TK) inhibitor 8 (LLE = 2.1) to produce the development candidate axitinib (9) was recently reported [17]. 

B.K., Yu, S. and Hartman, G.D. (2004) Potent N-(l,3-thiazoyl-2-yl)pyridine-2-amine vascular endothelial growth factor receptor tyrosine kinase inhibitors with excellent pharmacokinetics and low affinity for the hERG ion channel. Journal of Medicinal Chemistry, 47, 6363-6372. 

Recent studies have demonstrated that overexpression of HDACl represses the tumor suppressors, p53 and von Hippel-Lindau (VHL), but induces the hypoxia-responsive genes, hypoxia inducible factor alpha (HIF-la) and vascular endothelial growth factor (VEGF) and increases angiogenesis. Conversely, HDAC inhibitors derepress the tumor suppressors, p53 and VHL, and repress HIF-la and VEGF [68, 69]. 

Nusgens, B.V and Castronovo, V. (2002) Histone deacetylases inhibitors as anti-angiogenic agents altering vascular endothelial growth factor signaling. Oncogene, 21, 427-436. 

Development of Angiogenesis Inhibitors to Vascular Endothelial Growth Factor Receptor 2 for Cancer Therapy... 

Schlaeppi JM, Wood JM. Targeting vascular endothelial growth factor (VEGF) for anti-tumor therapy, by anti-VEGF neutralizing monoclonal antibodies or by VEGF receptor tyrosine kinase inhibitors. Cancer Metastasis Rev 1999 18 4734-81. 

Fong TAT, Shawver LK, Sun L, et al. SU5416 is a potent and selective inhibitor of the vascular endothelial growth factor receptor (Flk-l/KDR) that inhibits tyrosine kinase catalysis, tumor vascularization, and growth of multiple tumor types. Cancer Res 1999 59 99-106. 

Wedge SR, Ogilvie DJ, Dukes M, Kendrew J, Curwen JO, Hennequin LF, et al. ZD4190 an orally active inhibitor of vascular endothelial growth factor signaling with broad-spectrum antitumor efficacy. Cancer Res 2000 60 970-975. 

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