{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T08:31:08Z","timestamp":1789029068656,"version":"build-2803163510"},"reference-count":14,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,8,31]],"date-time":"2021-08-31T00:00:00Z","timestamp":1630368000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"},{"start":{"date-parts":[[2021,8,31]],"date-time":"2021-08-31T00:00:00Z","timestamp":1630368000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"}],"funder":[{"DOI":"10.13039\/501100001809","name":"national natural science foundation of china","doi-asserted-by":"publisher","award":["82073872"],"award-info":[{"award-number":["82073872"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Invest New Drugs"],"published-print":{"date-parts":[[2022,2]]},"DOI":"10.1007\/s10637-021-01169-4","type":"journal-article","created":{"date-parts":[[2021,8,31]],"date-time":"2021-08-31T12:02:52Z","timestamp":1630411372000},"page":"10-20","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Design, synthesis and biological evaluation of dual HDAC and VEGFR inhibitors as multitargeted anticancer agents"],"prefix":"10.1007","volume":"40","author":[{"given":"Xia","family":"Xue","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingjie","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongxiang","family":"Liao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deqing","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lina","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongjie","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun","family":"Luan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6230-709X","authenticated-orcid":false,"given":"Xiaogang","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,8,31]]},"reference":[{"key":"1169_CR1","doi-asserted-by":"publisher","first-page":"650","DOI":"10.1056\/NEJMra1805035","volume":"383","author":"SE Bates","year":"2020","unstructured":"Bates SE (2020) Epigenetic Therapies for Cancer. N Engl J Med 383:650\u2013663","journal-title":"N Engl J Med"},{"key":"1169_CR2","doi-asserted-by":"publisher","first-page":"1373","DOI":"10.1002\/med.21437","volume":"37","author":"C Zagni","year":"2017","unstructured":"Zagni C, Floresta G, Monciino G, Rescifina A (2017) The search for potent, small-molecule HDACIs in cancer treatment: a decade after Vorinostat. Med Res Rev 37:1373\u20131428","journal-title":"Med Res Rev"},{"key":"1169_CR3","doi-asserted-by":"publisher","first-page":"1216","DOI":"10.1021\/acs.chemrev.7b00181","volume":"118","author":"I Ali","year":"2018","unstructured":"Ali I, Conrad RJ, Verdin E, Ott M (2018) Lysine Acetylation Goes Global: From Epigenetics to Metabolism and Therapeutics. Chem Rev 118:1216\u20131252","journal-title":"Chem Rev"},{"key":"1169_CR4","doi-asserted-by":"crossref","unstructured":"Wu P, Nielsen TE, Clausen MH (2015) FDA-approved small-molecule kinase inhibitors.Trends Pharmacol Sci 36:422\u2013439","DOI":"10.1016\/j.tips.2015.04.005"},{"key":"1169_CR5","doi-asserted-by":"publisher","first-page":"10797","DOI":"10.1021\/jm301085w","volume":"55","author":"F Musumeci","year":"2012","unstructured":"Musumeci F, Radi M, Brullo C, Schenone S (2012) Vascular endothelial growth factor (VEGF) receptors: drugs and new inhibitors. J Med Chem 55:10797\u201310822","journal-title":"J Med Chem"},{"key":"1169_CR6","doi-asserted-by":"publisher","first-page":"1814","DOI":"10.1056\/NEJMoa1510016","volume":"373","author":"TK Choueiri","year":"2015","unstructured":"Choueiri TK, Escudier B, Powles T, Mainwaring PN, Rini BI, Donskov F, Hammers H, Hutson TE, Lee JL, Peltola K, Roth BJ, Bjarnason GA, G\u00e9czi L, Keam B, Maroto P, Heng DY, Schmidinger M, Kantoff PW, Borgman-Hagey A, Hessel C, Scheffold C, Schwab GM, Tannir NM, Motzer RJ, Investigators METEOR (2015) Cabozantinib versus Everolimus in Advanced Renal-Cell Carcinoma. N Engl J Med 373:1814\u20131823","journal-title":"N Engl J Med"},{"key":"1169_CR7","doi-asserted-by":"publisher","first-page":"130","DOI":"10.1016\/j.jprot.2017.08.015","volume":"170","author":"S Vyse","year":"2018","unstructured":"Vyse S, McCarthy F, Broncel M, Paul A, Wong JP, Bhamra A, Huang PH (2018) Quantitative phosphoproteomic analysis of acquired cancer drug resistance to pazopanib and dasatinib. J Proteomics 170:130\u2013140","journal-title":"J Proteomics"},{"key":"1169_CR8","doi-asserted-by":"publisher","first-page":"1507","DOI":"10.1007\/s00432-013-1465-6","volume":"139","author":"D Chan","year":"2013","unstructured":"Chan D, Zheng Y, Tyner JW, Chng WJ, Chien WW, Gery S, Leong G, Braunstein GD, Koeffler HP (2013) Belinostat and panobinostat (HDACI): in vitro and in vivo studies in thyroid cancer. J Cancer Res Clin Oncol 139:1507\u20131514","journal-title":"J Cancer Res Clin Oncol"},{"key":"1169_CR9","doi-asserted-by":"publisher","first-page":"16367","DOI":"10.18632\/oncotarget.14829","volume":"8","author":"L Booth","year":"2017","unstructured":"Booth L, Roberts JL, Sander C, Lee J, Kirkwood JM, Poklepovic A, Dent P (2017) The HDAC inhibitor AR42 interacts with pazopanib to kill trametinib\/dabrafenib-resistant melanoma cells in vitro and in vivo. Oncotarget 8:16367\u201316386","journal-title":"Oncotarget"},{"key":"1169_CR10","doi-asserted-by":"publisher","first-page":"578","DOI":"10.4161\/cbt.28163","volume":"15","author":"S Tavallai","year":"2014","unstructured":"Tavallai S, Hamed HA, Grant S, Poklepovic A, Dent P (2014) Pazopanib and HDAC inhibitors interact to kill sarcoma cells. Cancer Biol Ther 15:578\u2013585","journal-title":"Cancer Biol Ther"},{"issue":"11","key":"1169_CR11","doi-asserted-by":"publisher","first-page":"1231","DOI":"10.1200\/JCO.2016.70.5350","volume":"35","author":"R Aggarwal","year":"2017","unstructured":"Aggarwal R, Thomas S, Pawlowska N, Bartelink I, Grabowsky J, Jahan T, Cripps A, Harb A, Leng J, Reinert A, Mastroserio I, Truong TG, Ryan CJ, Munster PN (2017) Inhibiting Histone Deacetylase as a Means to Reverse Resistance to Angiogenesis Inhibitors: Phase I Study of Abexinostat Plus Pazopanib in Advanced Solid Tumor Malignancies. J Clin Oncol 35(11):1231\u20131239. https:\/\/doi.org\/10.1200\/JCO.2016.70.5350","journal-title":"J Clin Oncol"},{"key":"1169_CR12","doi-asserted-by":"publisher","first-page":"5304","DOI":"10.1021\/acs.jmedchem.8b00384","volume":"61","author":"J Zang","year":"2018","unstructured":"Zang J, Liang X, Huang Y, Jia Y, Li X, Xu W, Chou CJ, Zhang Y (2018) Discovery of Novel Pazopanib-Based HDAC and VEGFR Dual Inhibitors Targeting Cancer Epigenetics and Angiogenesis Simultaneously. J Med Chem 61:5304\u20135322","journal-title":"J Med Chem"},{"key":"1169_CR13","doi-asserted-by":"publisher","first-page":"9942","DOI":"10.1021\/acs.jmedchem.6b01385","volume":"59","author":"JJ McClure","year":"2016","unstructured":"McClure JJ, Zhang C, Inks ES, Peterson YK, Li J, Chou CJ (2016) Development of Allosteric Hydrazide-Containing Class I Histone Deacetylase Inhibitors for Use in Acute Myeloid Leukemia. J Med Chem 59:9942\u20139959","journal-title":"J Med Chem"},{"key":"1169_CR14","doi-asserted-by":"publisher","first-page":"297","DOI":"10.2183\/pjab.93.019","volume":"93","author":"M Yoshida","year":"2017","unstructured":"Yoshida M, Kudo N, Kosono S, Ito A (2017) Chemical and structural biology of protein lysine deacetylases. Proc Jpn Acad Ser B Phys Biol Sci 93:297\u2013321","journal-title":"Proc Jpn Acad Ser B Phys Biol Sci"}],"container-title":["Investigational New Drugs"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10637-021-01169-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s10637-021-01169-4\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10637-021-01169-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,3,11]],"date-time":"2023-03-11T04:39:09Z","timestamp":1678509549000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s10637-021-01169-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,8,31]]},"references-count":14,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2022,2]]}},"alternative-id":["1169"],"URL":"https:\/\/doi.org\/10.1007\/s10637-021-01169-4","relation":{},"ISSN":["0167-6997","1573-0646"],"issn-type":[{"value":"0167-6997","type":"print"},{"value":"1573-0646","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,8,31]]},"assertion":[{"value":"23 June 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"18 August 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"31 August 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"This article does not contain any studies with human participants or animals performed by any of the authors.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}