1623819-94-2Relevant academic research and scientific papers
Rational Design of Suprastat: A Novel Selective Histone Deacetylase 6 Inhibitor with the Ability to Potentiate Immunotherapy in Melanoma Models
Noonepalle, Satish,Shen, Sida,Ptá?ek, Jakub,Tavares, Maurício T.,Zhang, Guiping,Stránsky, Jan,Pavlí?ek, Ji?í,Ferreira, Glaucio M.,Hadley, Melissa,Pelaez, Guido,Ba?inka, Cyril,Kozikowski, Alan P.,Villagra, Alejandro
, p. 10246 - 10262 (2020)
Selective inhibition of histone deacetylase 6 (HDAC6) is being recognized as a therapeutic approach for cancers. In this study, we designed a new HDAC6 inhibitor, named Suprastat, using in silico simulations. X-ray crystallography and molecular dynamics simulations provide strong evidence to support the notion that the aminomethyl and hydroxyl groups in the capping group of Suprastat establish significant hydrogen bond interactions, either direct or water-mediated, with residues D460, N530, and S531, which play a vital role in regulating the deacetylase function of the enzyme and which are absent in other isoforms. In vitro characterization of Suprastat demonstrates subnanomolar HDAC6 inhibitory potency and a hundred- to a thousand-fold HDAC6 selectivity over the other HDAC isoforms. In vivo studies reveal that a combination of Suprastat and anti-PD1 immunotherapy enhances antitumor immune response, mediated by a decrease of protumoral M2 macrophages and increased infiltration of antitumor CD8+ effector and memory T-cells.
Reductive Amination Revisited: Reduction of Aldimines with Trichlorosilane Catalyzed by Dimethylformamide─Functional Group Tolerance, Scope, and Limitations
Campbell, Joanna L. P.,Davies, Christopher D.,Ho?ek, Jan,Ko?ovsky, Pavel,Kysilka, Ond?ej,Popov, Kirill K.,Pour, Milan
, p. 920 - 943 (2022/01/27)
Aldimines, generated in situ from aliphatic, aromatic, and heteroaromatic aldehydes and aliphatic, aromatic, and heteroaromatic primary or secondary amines, can be reduced with trichlorosilane in the presence of dimethylformamide (DMF) as an organocatalys
Tunable Synthesis of α-Amino Boronic Esters from Available Aldehydes and Amines through Sequential One-Pot Dehydration and Copper-Catalyzed Borylacylation
Xia, Qi,Chang, Hua-Rong,Li, Juan,Wang, Jia-Yi,Peng, Yan-Qing,Song, Gong-Hua
, p. 2716 - 2724 (2020/01/31)
Copper-catalyzed multicomponent borylacylation of imines with acid chlorides and bis(pinacolato)diboron was developed for the preparation of synthetically useful and pharmacologically relevant α-amino boronic acid derivatives. Starting from a range of acid chlorides and imines with aryl, heteroaryl, and alkyl substituents, most of these ligand-free reactions proceeded smoothly at room temperature in moderate to good yields. Furthermore, a facile and convenient one-pot, multistep access to the direct synthesis of α-amino boronic acid derivatives from available aldehydes and amines was also developed.
Design and Synthesis of C3-Substituted β-Carboline-Based Histone Deacetylase Inhibitors with Potent Antitumor Activities
Ling, Yong,Feng, Jiao,Luo, Lin,Guo, Jing,Peng, Yanfu,Wang, Tingting,Ge, Xiang,Xu, Qibing,Wang, Xinyang,Dai, Hong,Zhang, Yanan
supporting information, p. 646 - 651 (2017/05/15)
A series of hydroxamic acid histone deacetylase (HDAC) inhibitors in which the β-carboline motif has been incorporated were designed and synthesized. The effect of substitution at the C3 amide on HDAC inhibition and antiproliferative activities was invest
Development of novel β-carboline-based hydroxamate derivatives as HDAC inhibitors with DNA damage and apoptosis inducing abilities
Liu, Ji,Wang, Tingting,Wang, Xinyang,Luo, Lin,Guo, Jing,Peng, Yanfu,Xu, Qibing,Miao, Jiefei,Zhang, Yanan,Ling, Yong
supporting information, p. 1213 - 1219 (2017/07/11)
A series of novel β-carboline-based hydroxamate derivatives (8a-n) as HDAC inhibitors have been designed and synthesized. Most of these compounds displayed potent histone deacetylase inhibitory effects and good antiproliferative activity with IC50/s
