title: Recent Advances in the Discovery of HIF-1α-p300/CBP Inhibitors as Anti-Cancer Agents.
abstract: Hypoxia-inducible factor-1 (HIF-1), a heterodimeric (containing α and β subunits) transcription factor, is involved in hypoxia response pathway that regulates the expression of many tumorrelated genes. The stabilized HIF-1 heterodimer couples to the general co-activators p300/CBP (CREB binding protein), forming an active transcription factor to initiate hypoxic responses. Inhibiting the transcription factor-coactivator HIF-1α-p300/CBP interaction represents an attractive approach for blocking hypoxia pathway in tumors. Recently, diverse HIF-1α-p300/CBP inhibitors have been designed and their anti-tumor activities have been evaluated. The developments of inhibitors of HIF-1α- p300/CBP are discussed in this review. An outline of structures and biological activities of these inhibitors can be traced, along with the approaches for inhibitors discovery. The challenges in identifying novel and selective potent inhibitors of HIF-1α-p300/CBP are also put forward.
authors.affiliation: Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing 210009, P.R. China.|State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, P.R. China.
authors.forename: Jinlian
authors.initials: J
authors.lastname: Wei
authors.affiliation: Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing 210009, P.R. China.|State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, P.R. China.
authors.forename: Yingrui
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing 210009, P.R. China.|State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, P.R. China.
authors.forename: Mengchen
authors.initials: M
authors.lastname: Lu
authors.affiliation: Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing 210009, P.R. China.|State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, P.R. China.
authors.forename: Yonghua
authors.initials: Y
authors.lastname: Lei
authors.affiliation: Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing 210009, P.R. China.|State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, P.R. China.
authors.forename: Lili
authors.initials: L
authors.lastname: Xu
authors.affiliation: Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing 210009, P.R. China.|State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, P.R. China.
authors.forename: Zhengyu
authors.initials: Z
authors.lastname: Jiang
authors.affiliation: Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing 210009, P.R. China.|State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, P.R. China.
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Xu
authors.affiliation: Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing 210009, P.R. China.|State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, P.R. China.
authors.forename: Xiaoke
authors.initials: X
authors.lastname: Guo
authors.affiliation: Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing 210009, P.R. China.|State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, P.R. China.|Department of Organic Chemistry, School of Science, China Pharmaceutical University, Nanjing 210009, P.R. China.
authors.forename: Xiaojin
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing 210009, P.R. China.|State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, P.R. China.|Department of Medicinal Chemistry, School of Pharmacy, China Pharmaceutical University, Nanjing 210009, P.R. China.
authors.forename: Haopeng
authors.initials: H
authors.lastname: Sun
authors.affiliation: Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing 210009, P.R. China.|State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, P.R. China.
authors.forename: Qidong
authors.initials: Q
authors.lastname: You
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D051784:Aryl Hydrocarbon Receptor Nuclear Translocator / Q000037:antagonists & inhibitors*; D050882:CREB-Binding Protein / Q000037:antagonists & inhibitors*; D049109:Cell Proliferation / Q000187:drug effects; D055808:Drug Discovery; D050881:E1A-Associated p300 Protein / Q000037:antagonists & inhibitors*; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000037:antagonists & inhibitors*; D015394:Molecular Structure; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology
chemical_list: C497396:ARNT protein, human; D000970:Antineoplastic Agents; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D051784:Aryl Hydrocarbon Receptor Nuclear Translocator; D050882:CREB-Binding Protein; C494363:CREBBP protein, human; D050881:E1A-Associated p300 Protein; C494360:EP300 protein, human
keywords: Anticancer; HIF-1α/p300 inhibitors; cancer therapy; hypoxia response pathway; hypoxia-inducible factor-1; p300/CREB binding protein