Ju, Eun Ji Yeon, Seul Ki Park, Jong-Hyun Cheon, So Young Choi, Ji Won Ha, Taehwan Jang, Bo Ko Kim, Siwon Kang, Yong Gu Hwang, Hayoung Cho, Sung Jin Cheong, Eunji Bahn, Yong Sun Pae, Ae Nim Kim, Sung Min Park, Ki Duk 2024-01-20T05:00:58Z 2024-01-20T05:00:58Z 2021-09-04 2016-02-17 1860-7179 https://pubs.kist.re.kr/handle/201004/124377 Neuromyelitis optica (NMO) is a demyelinating autoimmune disease of the optic nerve and spinal cord triggered by binding of NMO-specific immunoglobulinG (NMO-IgG) auto-antibodies to the water channel aquaporin-4 (AQP4) in astrocytes. To find potential NMO therapeutics, a screening system was established and used to identify inhibitors of NMO-IgG-mediated complement-dependent cytotoxicity (CDC). The screening of approximately 400 compounds yielded potent hit compounds with inhibitory effects against CDC in U87-MG cells expressing human AQP4. Derivatives of the hit compounds were synthesized and evaluated for their inhibition of CDC. Of the small molecules synthesized, (E)-1-(2-((4-methoxyphenyl)sulfonyl)vinyl)-[4-[(3-trifluoromethyl)phenyl] methoxy]benzene (5c) showed the most potent activity in both stably transfected U87-MG cells and mice-derived astrocytes. The results of this study suggest that 5c, which targets NMO-IgG-specific CDC, may be useful as a research tool and a potential candidate for therapeutic development for the treatment of NMO. English WILEY-V C H VERLAG GMBH MULTIPLE-SCLEROSIS AQUAPORIN-4 ANTIBODIES IMMUNOGLOBULIN-G WATER CHANNEL IGG BINDING MECHANISMS BRAIN DISTINCTION DISCOVERY DISEASE Screening, Synthesis, and In Vitro Evaluation of Vinyl Sulfones as Inhibitors of Complement-Dependent Cytotoxicity in Neuromyelitis Optica Article 10.1002/cmdc.201500546 1 CHEMMEDCHEM, v.11, no.4, pp.377 - 381 CHEMMEDCHEM 11 4 377 381 scie scopus 000370738300005 2-s2.0-84958845782 Chemistry, Medicinal Pharmacology & Pharmacy Pharmacology & Pharmacy Article MULTIPLE-SCLEROSIS AQUAPORIN-4 ANTIBODIES IMMUNOGLOBULIN-G WATER CHANNEL IGG BINDING MECHANISMS BRAIN DISTINCTION DISCOVERY DISEASE aquaporin-4 complement-dependent cytotoxicity neuromyelitis optica NMO-specific immunoglobulinG autoantibodies vinyl sulfones