Lee, Ju-Hyeon Shin, Sang Chul Seo, Seon Hee Seo, Young Ho Jeong, Nakcheol Kim, Chan-Wha Kim, Eunice EunKyeong Keum, Gyochang 2024-01-20T02:31:30Z 2024-01-20T02:31:30Z 2021-09-04 2017-01-15 0960-894X https://pubs.kist.re.kr/handle/201004/123199 A novel series of heat shock protein 90 (Hsp90) inhibitors was identified by X-ray crystal analysis of complex structures at solvent-exposed exit pocket C. The 2-amino-pyrrolo[2,3-d]pyrimidine derivatives, 7-deazapurines substituted with a benzyl moiety at C5, showed potent Hsp90 inhibition and broadspectrum antiproliferative activity against NCI-60 cancer cell lines. The most potent compound, 6a, inhibited Hsp90 with an IC50 of 36 nM and showed a submicromolar mean GI(50) value against NCI-60 cell lines. The interaction of 6a at the ATP-binding pocket of Hsp90 was confirmed by X-ray crystallography and Western blot analysis. (C) 2016 Published by Elsevier Ltd. English Pergamon Press Ltd. SHOCK-PROTEIN 90 MOLECULAR CHAPERONE INHIBITORS CANCER-THERAPY ANTITUMOR-ACTIVITY MODELS DISCOVERY PATHWAYS BIIB021 TUMORS Synthesis and in vitro antiproliferative activity of C5-benzyl substituted 2-amino-pyrrolo[2,3-d]pyrimidines as potent Hsp90 inhibitors Article 10.1016/j.bmcl.2016.11.062 1 Bioorganic & Medicinal Chemistry Letters, v.27, no.2, pp.237 - 241 Bioorganic & Medicinal Chemistry Letters 27 2 237 241 scie scopus 000392558500024 2-s2.0-85006850831 Chemistry, Medicinal Chemistry, Organic Pharmacology & Pharmacy Chemistry Article SHOCK-PROTEIN 90 MOLECULAR CHAPERONE INHIBITORS CANCER-THERAPY ANTITUMOR-ACTIVITY MODELS DISCOVERY PATHWAYS BIIB021 TUMORS Hsp90 Structure-based design Cancer Antiproliferative Pyrrolo[2,3-d]pyrimidines