@article {KANG4929, author = {CHUNG HYO KANG and SANG UN CHOI and YOU HWA SON and HEUNG KYOUNG LEE and HYE GWANG JEONG and CHANG-SOO YUN and SUNJOO AHN and CHI HOON PARK}, title = {Discovery of a Novel Chemical Scaffold Against Mutant Isocitrate Dehydrogenase 1 (IDH1)}, volume = {40}, number = {9}, pages = {4929--4935}, year = {2020}, doi = {10.21873/anticanres.14496}, publisher = {International Institute of Anticancer Research}, abstract = {Background: Mutations in the isocitrate dehydrogenase 1 (IDH1) gene are frequently found in various cancer types. IDH1 mutants produce 2-hydroxyglutarate (2-HG), an oncometabolite, from alpha-ketoglutarate (α-KG). This 2-HG plays a key role in tumorigenesis via inhibition of α-KG dependent enzymes. For this reason, IDH1 mutant could be an ideal target for the treatment of cancer. Materials and Methods: To find a new IDH1 inhibitor, 8,364 compounds were obtained from Korea Chemical Bank. Using high-throughput screening (HTS) of a chemical library, we unveiled a compound that could inhibit the IDH1 mutant. Results: According to the enzyme assay, our compound (KRC-09) effectively inhibited the activity of IDH1 R132H mutant. In addition, KRC-09 decreased the concentration of intracellular 2-HG in the U-87 MG cell line harboring IDH1 R132H. Conclusion: In this article, we present a novel chemical scaffold that suppresses the activity of an IDH1 mutant.}, issn = {0250-7005}, URL = {https://ar.iiarjournals.org/content/40/9/4929}, eprint = {https://ar.iiarjournals.org/content/40/9/4929.full.pdf}, journal = {Anticancer Research} }