title: Adnectin-targeted inhibitors: rationale and results.
abstract: Adnectins are a family of binding proteins derived from the 10th type III domain of human fibronectin (10Fn3), which is part of the immunoglobulin superfamily and normally binds integrin. The 10Fn3 has the potential for broad therapeutic applications given its structural stability, ability to be manipulated, and its abundance in the human body. The most commonly studied adnectin is CT-322, which is an inhibitor of vascular endothelial growth factor receptor-2. A bispecific adnectin, El-Tandem, has also been developed and binds to epidermal growth factor receptor and insulin-like growth factor-1 receptor simultaneously. Pre-clinical studies have shown promising results in relation to reducing tumor growth, decreasing microvessel density, and promoting normalization of tumor architecture. The phase I trial with CT-322 demonstrates relatively low toxicities. However, the phase II study done with CT-322 in recurrent glioblastoma does not reveal as promising results.
authors.affiliation: Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, 8700 Beverly Blvd, Los Angeles, CA, 90048, USA, esha.sachdev@cshs.org.
authors.forename: Esha
authors.initials: E
authors.lastname: Sachdev
authors.forename: Jun
authors.initials: J
authors.lastname: Gong
authors.forename: Bobbie
authors.initials: B
authors.lastname: Rimel
authors.forename: Monica
authors.initials: M
authors.lastname: Mita
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000069286:Bortezomib / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D004353:Drug Evaluation, Preclinical; D005353:Fibronectins / Q000627:therapeutic use*; D006801:Humans; D000077269:Lenalidomide; D058990:Molecular Targeted Therapy / Q000379:methods*; D009369:Neoplasms / Q000188:drug therapy*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010880:Piperidines; D011720:Pyrazoles / Q000627:therapeutic use; D011743:Pyrimidines / Q000627:therapeutic use; D013792:Thalidomide / Q000031:analogs & derivatives / Q000627:therapeutic use; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000037:antagonists & inhibitors*
chemical_list: D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D005353:Fibronectins; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010880:Piperidines; D011720:Pyrazoles; D011743:Pyrimidines; C551803:ibrutinib; D013792:Thalidomide; D000069286:Bortezomib; D040301:Vascular Endothelial Growth Factor Receptor-2; D000077269:Lenalidomide; D000225:Adenine