title: Novel scaffold evolution through combinatorial 3D-QSAR model studies of two types of JNK3 inhibitors.
abstract: JNK3 is an emerging target for neurodegenerative diseases including AD and PD, with histological selectivity. Specifically, in AD, JNK3 is the main protein kinase for APP phosphorylation, which is an important mechanism for Aβ processing, and a biomarker of Alzheimer's disease. Therefore, targeting JNK3 is a reasonable strategy for drug discovery in neurodegenerative diseases. In order to find a novel scaffold for JNK3 inhibitors, we performed 3D-QSAR modeling studies with two different JNK3 inhibitor series. The CoMFA model was obtained with a q2value of 0.806 and an r2value of 0.850. Based on CoMFA and CoMSIA models, rational design was conducted and led to a novel scaffold, N-(thiophen-2-yl)-8H-pyrazolo[1,5-a]pyrido[1,2-c]pyrimidine-10-carboxamide.
authors.affiliation: Department of Pharmacy, College of Pharmacy & Institute of Pharmaceutical Science and Technology, Hanyang University, 55 Hanyangdaehak-ro, Sangnok-gu, Ansan, Gyeonggi-do 426-791, Republic of Korea.
authors.forename: Hoyong
authors.initials: H
authors.lastname: Jung
authors.affiliation: Department of Pharmacy, College of Pharmacy & Institute of Pharmaceutical Science and Technology, Hanyang University, 55 Hanyangdaehak-ro, Sangnok-gu, Ansan, Gyeonggi-do 426-791, Republic of Korea; Kohat University of Science & Technology, Kohat, Khyber Pukhtunkhwa, Pakistan.
authors.forename: Waqar
authors.initials: W
authors.lastname: Aman
authors.affiliation: Department of Pharmacy, College of Pharmacy & Institute of Pharmaceutical Science and Technology, Hanyang University, 55 Hanyangdaehak-ro, Sangnok-gu, Ansan, Gyeonggi-do 426-791, Republic of Korea. Electronic address: jhah@hanyang.ac.kr.
authors.forename: Jung-Mi
authors.initials: JM
authors.lastname: Hah
mesh_terms: D015195:Drug Design; D006801:Humans; D020128:Inhibitory Concentration 50; D048057:Mitogen-Activated Protein Kinase 10 / Q000737:chemistry / Q000378:metabolism*; D008958:Models, Molecular; D047428:Protein Kinase Inhibitors / Q000737:chemistry* / Q000378:metabolism; D021281:Quantitative Structure-Activity Relationship
chemical_list: D047428:Protein Kinase Inhibitors; D048057:Mitogen-Activated Protein Kinase 10
keywords: 3D-QSAR; JNK3; Neurodegenerative disease