Jang, Jae Wan Song, Chi Man Choi, Kee Hyun Cho, Yong Seo Baek, Du-Jong Shin, Kye Jung Pae, Ae Nim 2024-01-20T17:35:09Z 2024-01-20T17:35:09Z 2021-09-02 2011-01-20 0253-2964 https://pubs.kist.re.kr/handle/201004/130725 Human ether-a-go-go related gene (hERG) potassium channel blockade, an undesirable side effect which might cause sudden cardiac death, is one of the major concerns facing the pharmaceutical industry. The purpose of this study is to develop an in silico QSAR model which uncovers the structural parameters of T-type calcium channel blockers to reduce hERG blockade. Comparative molecular similarity indices analysis (CoMSIA) was conducted on a series of piperazine and benzimidazole derivatives bearing methyl 5-(ethyl(methyl)amino)-2-isopropyl-2-phenylpentanoate moieties, which was synthesized by our group. Three different alignment methods were applied to obtain a reliable model: ligand based alienment, pharmacophore based alignment, and receptor guided alignment. The CoMSIA model with receptor guided alignment yielded the best results : r(2) = 0.955, q(2) = 0.781, r(pred)(2) = 0.758. The generated CoMSIA contour maps using electrostatic, hydrophobic, H-bond donor, and acceptor fields explain well the structural requirements for h ERG non-blockers and also correlate with the lipophilic potential map of the hERG channel pore. English WILEY-V C H VERLAG GMBH LONG-QT-SYNDROME MOLECULAR SIMILARITY INDEXES VECTOR MACHINE METHOD POTASSIUM CHANNEL K+ CHANNEL DRUG-BINDING QSAR MODEL 3D QSAR CLASSIFICATION MODEL CARDIAC-ARRHYTHMIA In silico Analysis on hERG Channel Blocking Effect of a Series of T-type Calcium Channel Blockers Article 10.5012/bkcs.2011.32.1.251 1 BULLETIN OF THE KOREAN CHEMICAL SOCIETY, v.32, no.1, pp.251 - 262 BULLETIN OF THE KOREAN CHEMICAL SOCIETY 32 1 251 262 scie scopus kci ART001521246 000286538600046 2-s2.0-78951484777 Chemistry, Multidisciplinary Chemistry Article LONG-QT-SYNDROME MOLECULAR SIMILARITY INDEXES VECTOR MACHINE METHOD POTASSIUM CHANNEL K+ CHANNEL DRUG-BINDING QSAR MODEL 3D QSAR CLASSIFICATION MODEL CARDIAC-ARRHYTHMIA hERG T-type calcium channel blockers CoMSIA