937271-47-1Relevant academic research and scientific papers
Discovery of KDM5A inhibitors: Homology modeling, virtual screening and structure-activity relationship analysis
Wu, Xiaoai,Fang, Zhen,Yang, Bo,Zhong, Lei,Yang, Qiuyuan,Zhang, Chunhui,Huang, Shenzhen,Xiang, Rong,Suzuki, Takayoshi,Li, Lin-Li,Yang, Sheng-Yong
supporting information, p. 2284 - 2288 (2016/04/20)
Herein we report the discovery of a series of new KDM5A inhibitors. A three-dimensional (3D) structure model of KDM5A jumonji domain was firstly established based on homology modeling. Molecular docking-based virtual screening was then performed against c
Discovery of kinase spectrum selective macrocycle (16E)-14-methyl-20-oxa-5, 7,14,26-tetraazatetracyclo[19.3.1.1(2,6).1(8,12)]heptacosa-1(25),2(26),3,5,8(27) ,9,11,16,21,23-decaene (SB1317/TG02), a potent inhibitor of cyclin dependent kinases (CDKs), Janus kinase 2 (JAK2), and Fms-like tyrosine kinase-3 (FLT3) for the treatment of cancer
William, Anthony D.,Lee, Angeline C.-H.,Goh, Kee Chuan,Blanchard, Stéphanie,Poulsen, Anders,Teo, Ee Ling,Nagaraj, Harish,Lee, Chai Ping,Wang, Haishan,Williams, Meredith,Sun, Eric T.,Hu, Changyong,Jayaraman, Ramesh,Pasha, Mohammed Khalid,Ethirajulu, Kantharaj,Wood, Jeanette M.,Dymock, Brian W.
experimental part, p. 169 - 196 (2012/03/12)
Herein, we describe the design, synthesis, and SAR of a series of unique small molecule macrocycles that show spectrum selective kinase inhibition of CDKs, JAK2, and FLT3. The most promising leads were assessed in vitro for their inhibition of cancer cell proliferation, solubility, CYP450 inhibition, and microsomal stability. This screening cascade revealed 26h as a preferred compound with target IC50 of 13, 73, and 56 nM for CDK2, JAK2 and FLT3, respectively. Pharmacokinetic (PK) studies of 26h in preclinical species showed good oral exposures. Oral efficacy was observed in colon (HCT-116) and lymphoma (Ramos) xenograft studies, in line with the observed PK/PD correlation. 26h (SB1317/TG02) was progressed into development in 2010 and is currently undergoing phase 1 clinical trials in advanced leukemias and multiple myeloma.
Pyrimidine-based inhibitors of CaMKIIδ
Mavunkel, Babu,Xu, Yong-jin,Goyal, Bindu,Lim, Don,Lu, Qing,Chen, Zheng,Wang, Dan-Xiong,Higaki, Jeffrey,Chakraborty, Indrani,Liclican, Albert,Sideris, Steve,Laney, Maureen,Delling, Ulrike,Catalano, Rosanne,Higgins, Linda S.,Wang, Hui,Wang, Jing,Feng, Ying,Dugar, Sundeep,Levy, Daniel E.
, p. 2404 - 2408 (2008/09/21)
Non-ATP competitive pyrimidine-based inhibitors of CaMKIIδ were identified. Computational studies were enlisted to predict the probable mode of binding. The results of the computational studies led to the design of ATP competitive inhibitors with optimized hinge interactions. Inhibitors of this class possessed improved enzyme and cellular activity compared to early leads.
