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Effective chemotherapeutic strategies are currently lacking which combat this deadly disease curatively. The glioma-specific chloride ion channel represents a specific target for therapy. Chlorotoxin (CTX), a peptide derived from scorpion venom, has been shown to be specific and efficacious in blocking glioma Cl<jats:sup>\u2212<\/jats:sup> channel activity. Here, we report on two new derivatives (termed CA4 and CTX-23) designed and generated on the basis of the peptide sequence alignments of CTX and BmKCT. The novel peptides CA4 and CTX-23 are both effective in reducing glioma cell proliferation. In addition, CTX, CA4 and CTX-23 impact on cell migration and spheroid migration. These effects are accompanied by diminished cell extensions and increased nuclear sizes. Furthermore, we found that CA4 and CTX-23 are selective with low toxicity against primary neurons and astrocytes. In the <jats:italic>ex vivo<\/jats:italic> VOGiM, which maintain the entire brain tumor microenvironment, both CTX and CA4 display anti-tumor activity and reduce tumor volume. Hence, CTX and CA4 reveal anti-angiogenic properties with endothelial and angiogenic hotspots disrupting activities. These data report on the identification of two novel CTX derivatives with multiple anti-glioma properties including anti-angiogenesis.<\/jats:p>","DOI":"10.1038\/srep19799","type":"journal-article","created":{"date-parts":[[2016,2,2]],"date-time":"2016-02-02T10:01:45Z","timestamp":1454407305000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Identification of two novel Chlorotoxin derivatives CA4 and CTX-23 with chemotherapeutic and anti-angiogenic potential"],"prefix":"10.1038","volume":"6","author":[{"given":"Tengfei","family":"Xu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zheng","family":"Fan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenxin","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"Dietel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingliang","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthias W.","family":"Beckmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jana K.","family":"Wrosch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Buchfelder","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilker Y.","family":"Eyupoglu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhijian","family":"Cao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolai E.","family":"Savaskan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2016,2,2]]},"reference":[{"key":"BFsrep19799_CR1","doi-asserted-by":"publisher","first-page":"1403","DOI":"10.1016\/0041-0101(91)90128-E","volume":"29","author":"JA DeBin","year":"1991","unstructured":"DeBin, J. 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