PMID- 30771432
OWN - NLM
STAT- In-Data-Review
LR  - 20190329
IS  - 1872-7980 (Electronic)
IS  - 0304-3835 (Linking)
VI  - 449
DP  - 2019 May 1
TI  - Identification and characterization of small molecule inhibitors of the ubiquitin
      ligases Siah1/2 in melanoma and prostate cancer cells.
PG  - 145-162
LID - S0304-3835(19)30084-9 [pii]
LID - 10.1016/j.canlet.2019.02.012 [doi]
AB  - Inhibition of ubiquitin ligases with small molecule remains a very challenging
      task, given the lack of catalytic activity of the target and the requirement of
      disruption of its interactions with other proteins. Siah1/2, which are E3
      ubiquitin ligases, are implicated in melanoma and prostate cancer and represent
      high-value drug targets. We utilized three independent screening approaches in
      our efforts to identify small-molecule Siah1/2 inhibitors: Affinity
      Selection-Mass Spectrometry, a protein thermal shift-based assay and an in silico
      based screen. Inhibitors were assessed for their effect on viability of melanoma 
      and prostate cancer cultures, colony formation, prolyl-hydroxylase-HIF1alpha
      signaling, expression of selected Siah2-related transcripts, and Siah2 ubiquitin 
      ligase activity. Several analogs were further characterized, demonstrating
      improved efficacy. Combination of the top hits identified in the different assays
      demonstrated an additive effect, pointing to complementing mechanisms that
      underlie each of these Siah1/2 inhibitors.
CI  - Copyright (c) 2019 Elsevier B.V. All rights reserved.
FAU - Feng, Yongmei
AU  - Feng Y
AD  - Cancer Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, 
      92037, USA.
FAU - Sessions, E Hampton
AU  - Sessions EH
AD  - Cancer Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, 
      92037, USA.
FAU - Zhang, Fan
AU  - Zhang F
AD  - Vancouver Prostate Centre and Department of Urologic Sciences, University of
      British Columbia, Vancouver, British Columbia, Canada.
FAU - Ban, Fuqiang
AU  - Ban F
AD  - Vancouver Prostate Centre and Department of Urologic Sciences, University of
      British Columbia, Vancouver, British Columbia, Canada.
FAU - Placencio-Hickok, Veronica
AU  - Placencio-Hickok V
AD  - Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, 90048, USA.
FAU - Ma, Chen-Ting
AU  - Ma CT
AD  - Cancer Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, 
      92037, USA.
FAU - Zeng, Fu-Yue
AU  - Zeng FY
AD  - Cancer Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, 
      92037, USA.
FAU - Pass, Ian
AU  - Pass I
AD  - Cancer Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, 
      92037, USA.
FAU - Terry, David B
AU  - Terry DB
AD  - Cancer Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, 
      92037, USA.
FAU - Cadwell, Gregory
AU  - Cadwell G
AD  - Cancer Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, 
      92037, USA.
FAU - Bankston, Laurie A
AU  - Bankston LA
AD  - Cancer Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, 
      92037, USA.
FAU - Liddington, Robert C
AU  - Liddington RC
AD  - Cancer Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, 
      92037, USA.
FAU - Chung, Thomas D Y
AU  - Chung TDY
AD  - Cancer Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, 
      92037, USA.
FAU - Pinkerton, Anthony B
AU  - Pinkerton AB
AD  - Cancer Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, 
      92037, USA.
FAU - Sergienko, Eduard
AU  - Sergienko E
AD  - Cancer Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, 
      92037, USA.
FAU - Gleave, Martin
AU  - Gleave M
AD  - Vancouver Prostate Centre and Department of Urologic Sciences, University of
      British Columbia, Vancouver, British Columbia, Canada.
FAU - Bhowmick, Neil A
AU  - Bhowmick NA
AD  - Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, 90048, USA.
FAU - Jackson, Michael R
AU  - Jackson MR
AD  - Cancer Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, 
      92037, USA.
FAU - Cherkasov, Artem
AU  - Cherkasov A
AD  - Vancouver Prostate Centre and Department of Urologic Sciences, University of
      British Columbia, Vancouver, British Columbia, Canada.
FAU - Ronai, Ze'ev A
AU  - Ronai ZA
AD  - Cancer Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, 
      92037, USA. Electronic address: zeev@ronailab.net.
LA  - eng
GR  - P01 CA128814/CA/NCI NIH HHS/United States
PT  - Journal Article
DEP - 20190214
PL  - Ireland
TA  - Cancer Lett
JT  - Cancer letters
JID - 7600053
PMC - PMC6411447
MID - NIHMS1521739
OTO - NOTNLM
OT  - Melanoma
OT  - Prostate cancer
OT  - Siah1
OT  - Siah2
OT  - Ubiquitin ligase
EDAT- 2019/02/17 06:00
MHDA- 2019/02/17 06:00
CRDT- 2019/02/17 06:00
PMCR- 2020/05/01 00:00
PHST- 2018/10/19 00:00 [received]
PHST- 2018/12/10 00:00 [revised]
PHST- 2019/02/10 00:00 [accepted]
PHST- 2020/05/01 00:00 [pmc-release]
PHST- 2019/02/17 06:00 [pubmed]
PHST- 2019/02/17 06:00 [medline]
PHST- 2019/02/17 06:00 [entrez]
AID - S0304-3835(19)30084-9 [pii]
AID - 10.1016/j.canlet.2019.02.012 [doi]
PST - ppublish
SO  - Cancer Lett. 2019 May 1;449:145-162. doi: 10.1016/j.canlet.2019.02.012. Epub 2019
      Feb 14.