Shrestha, Aarajana Kim, Nayeon Lee, Su-Jeong Jeon, Yong Hyun Song, Ji-Joon An, Hongchan Cho, Sung Jin Kadayat, Tara Man Chin, Jungwook 2024-01-19T13:33:06Z 2024-01-19T13:33:06Z 2022-02-17 2021-10 0022-2623 https://pubs.kist.re.kr/handle/201004/116281 Nuclear receptor-binding SET domain (NSD) proteins are a class of histone lysine methyltransferases (HKMTases) that are amplified, mutated, translocated, or overexpressed in various types of cancers. Several campaigns to develop NSD inhibitors for cancer treatment have begun following recent advances in knowledge of NSD1, NSD2, and NSD3 structures and functions as well as the U.S. FDA approval of the first HKMTase inhibitor (tazemetostat, an EZH2 inhibitor) to treat follicular lymphoma and epithelioid sarcoma. This perspective highlights recent findings on the structures of catalytic su(var), enhancer-of-zeste, trithorax (SET) domains and other functional domains of NSD methyltransferases. In addition, recent progress and efforts to discover NSD-specific small molecule inhibitors against cancer-targeting catalytic SET domains, plant homeodomains, and proline-tryptophan-tryptophan-proline domains are summarized. English American Chemical Society Targeting the Nuclear Receptor-Binding SET Domain Family of Histone Lysine Methyltransferases for Cancer Therapy: Recent Progress and Perspectives Article 10.1021/acs.jmedchem.1c01116 1 Journal of Medicinal Chemistry, v.64, no.20, pp.14913 - 14929 Journal of Medicinal Chemistry 64 20 14913 14929 N scie scopus 000713412900001 2-s2.0-85115611067 Chemistry, Medicinal Pharmacology & Pharmacy Article SQUAMOUS-CELL CARCINOMA PROTEIN METHYLTRANSFERASES GENE-EXPRESSION POOR-PROGNOSIS NSD FAMILY MMSET METHYLATION WHSC1 PROLIFERATION METASTASIS Histone Lysine Methyltransferases Nuclear receptor-binding SET domain (NSD) Cancer Therapy