PMID- 37669603
OWN - NLM
STAT- MEDLINE
DCOM- 20230922
LR  - 20230925
IS  - 1464-3391 (Electronic)
IS  - 0968-0896 (Linking)
VI  - 93
DP  - 2023 Oct 1
TI  - Discovery of three-dimensional bicyclo[3.3.1]nonanols as novel heat shock protein 
      90 inhibitors.
PG  - 117463
LID - S0968-0896(23)00311-5 [pii]
LID - 10.1016/j.bmc.2023.117463 [doi]
AB  - We developed an efficient synthetic method for constructing bicyclo[3.3.1]nonane, 
      an sp(3)-carbon-rich three-dimensional scaffold consisting of two fused 
      six-membered rings. Among the bicyclo[3.3.1]nonanols synthesized, several 
      bicyclo[3.3.1]nonane derivatives were found to inhibit gene transcription by 
      hypoxia-inducible factor-1 (HIF-1). The structure-activity relationship study 
      revealed that the number of hydrophobic functional groups and a carboxylic acid 
      moiety in the bicyclo[3.3.1]nonanols are important for inhibitory activities of 
      both gene transcription by HIF-1 and cell growth. Bicyclo[3.3.1]nonanols 
      fluctuated the amounts of client proteins of heat shock protein (HSP) 90 without 
      inducing a heat shock response in cells and specifically inhibited the ATPase 
      activity of HSP90. These results indicate that bicyclo[3.3.1]nonanols are novel 
      HSP90 inhibitors with a different mechanism of action from conventional HSP90 
      inhibitors.
CI  - Copyright (c) 2023 Elsevier Ltd. All rights reserved.
FAU - Miura, Kazuki
AU  - Miura K
AD  - Laboratory for Chemistry and Life Science, Institute of Innovative Research, 
      Tokyo Institute of Technology, 4259 Nagatsuta-cho, Midori-ku, Yokohama 226-8503, 
      Japan.
FAU - Joshi, Manjusha
AU  - Joshi M
AD  - Laboratory for Chemistry and Life Science, Institute of Innovative Research, 
      Tokyo Institute of Technology, 4259 Nagatsuta-cho, Midori-ku, Yokohama 226-8503, 
      Japan.
FAU - Morita, Taiki
AU  - Morita T
AD  - Laboratory for Chemistry and Life Science, Institute of Innovative Research, 
      Tokyo Institute of Technology, 4259 Nagatsuta-cho, Midori-ku, Yokohama 226-8503, 
      Japan.
FAU - Nakamura, Hiroyuki
AU  - Nakamura H
AD  - Laboratory for Chemistry and Life Science, Institute of Innovative Research, 
      Tokyo Institute of Technology, 4259 Nagatsuta-cho, Midori-ku, Yokohama 226-8503, 
      Japan. Electronic address: hiro@res.titech.ac.jp.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20230829
PL  - England
TA  - Bioorg Med Chem
JT  - Bioorganic & medicinal chemistry
JID - 9413298
RN  - T9W3VH6G10 (nonane)
RN  - 0 (Alkanes)
RN  - 0 (Antineoplastic Agents)
RN  - 7440-44-0 (Carbon)
RN  - 0 (HSP90 Heat-Shock Proteins)
SB  - IM
MH  - Humans
MH  - *Alkanes
MH  - *Antineoplastic Agents
MH  - Carbon
MH  - HSP90 Heat-Shock Proteins
OTO - NOTNLM
OT  - ATPase inhibitor
OT  - Bicyclo[3.3.1]nonane
OT  - Heat shock protein 90 inhibitor
OT  - Three-dimensional compound
OT  - sp(3)-carbon-rich
COIS- Declaration of Competing Interest The authors declare that they have no known 
      competing financial interests or personal relationships that could have appeared 
      to influence the work reported in this paper.
EDAT- 2023/09/06 00:41
MHDA- 2023/09/22 06:42
CRDT- 2023/09/05 18:11
PHST- 2023/07/22 00:00 [received]
PHST- 2023/08/29 00:00 [revised]
PHST- 2023/08/29 00:00 [accepted]
PHST- 2023/09/22 06:42 [medline]
PHST- 2023/09/06 00:41 [pubmed]
PHST- 2023/09/05 18:11 [entrez]
AID - S0968-0896(23)00311-5 [pii]
AID - 10.1016/j.bmc.2023.117463 [doi]
PST - ppublish
SO  - Bioorg Med Chem. 2023 Oct 1;93:117463. doi: 10.1016/j.bmc.2023.117463. Epub 2023 
      Aug 29.