PMID- 28334506
OWN - NLM
STAT- MEDLINE
DCOM- 20170929
LR  - 20211204
IS  - 1860-7187 (Electronic)
IS  - 1860-7179 (Linking)
VI  - 12
IP  - 12
DP  - 2017 Jun 21
TI  - Molecular Features of the YAP Inhibitor Verteporfin: Synthesis of Hexasubstituted 
      Dipyrrins as Potential Inhibitors of YAP/TAZ, the Downstream Effectors of the 
      Hippo Pathway.
PG  - 954-961
LID - 10.1002/cmdc.201700063 [doi]
AB  - Porphyrin derivatives, in particular verteporfin (VP), a photosensitizer 
      initially designed for cancer therapy, have been identified as inhibitors of the 
      YAP-TEAD interaction and transcriptional activity. Herein we report the efficient 
      convergent synthesis of the dipyrrin half of protoporphyrin IX dimethyl ester 
      (PPIX-DME), in which the sensitive vinyl group was created at the final stage by 
      a dehydroiodination reaction. Two other dipyrrin derivatives were synthesized, 
      including dipyrrin 19 
      [(Z)-2-((3,5-dimethyl-4-vinyl-2H-pyrrol-2-ylidene)methyl)-3,5-dimethyl-4-vinyl-1H-pyrrole], 
      containing two vinyl groups. We found that VP and dipyrrin 19 showed significant 
      inhibitory effects on TEAD transcriptional activity in MDA-MB-231 human breast 
      cancer cells, whereas other compounds did not show significant changes. In 
      addition, we observed a marked decrease in both YAP and TAZ levels following VP 
      treatment, whereas dipyrrin 19 treatment primarily decreased the levels of YAP 
      and receptor kinase AXL, a downstream target of YAP. Together, our data suggest 
      that, due to their chemical structures, porphyrin- and dipyrrin-related 
      derivatives can directly target YAP and/or TAZ proteins and inhibit TEAD 
      transcriptional activity.
CI  - (c) 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.
FAU - Gibault, Floriane
AU  - Gibault F
AD  - Department of Onco and NeuroChemistry, University of Lille, INSERM UMR-S 1172, 
      Jean-Pierre Aubert Research Center, 3, rue du professeur Laguesse, BP 83, 59006, 
      Lille Cedex, France.
FAU - Bailly, Fabrice
AU  - Bailly F
AD  - Department of Onco and NeuroChemistry, University of Lille, INSERM UMR-S 1172, 
      Jean-Pierre Aubert Research Center, 3, rue du professeur Laguesse, BP 83, 59006, 
      Lille Cedex, France.
FAU - Corvaisier, Matthieu
AU  - Corvaisier M
AD  - Department of Mucins, Epithelial Differentiation and Carcinogenesis, University 
      of Lille, INSERM UMR-S 1172, Jean-Pierre Aubert Research Center, Batiment 
      Biserte, 1, place de Verdun, 59045, Lille Cedex, France.
FAU - Coevoet, Mathilde
AU  - Coevoet M
AD  - Department of Onco and NeuroChemistry, University of Lille, INSERM UMR-S 1172, 
      Jean-Pierre Aubert Research Center, 3, rue du professeur Laguesse, BP 83, 59006, 
      Lille Cedex, France.
FAU - Huet, Guillemette
AU  - Huet G
AD  - Department of Mucins, Epithelial Differentiation and Carcinogenesis, University 
      of Lille, INSERM UMR-S 1172, Jean-Pierre Aubert Research Center, Batiment 
      Biserte, 1, place de Verdun, 59045, Lille Cedex, France.
FAU - Melnyk, Patricia
AU  - Melnyk P
AUID- ORCID: 0000-0002-9555-3446
AD  - Department of Onco and NeuroChemistry, University of Lille, INSERM UMR-S 1172, 
      Jean-Pierre Aubert Research Center, 3, rue du professeur Laguesse, BP 83, 59006, 
      Lille Cedex, France.
FAU - Cotelle, Philippe
AU  - Cotelle P
AUID- ORCID: 0000-0003-0924-0433
AD  - Department of Onco and NeuroChemistry, University of Lille, INSERM UMR-S 1172, 
      Jean-Pierre Aubert Research Center, 3, rue du professeur Laguesse, BP 83, 59006, 
      Lille Cedex, France.
LA  - eng
PT  - Journal Article
DEP - 20170420
PL  - Germany
TA  - ChemMedChem
JT  - ChemMedChem
JID - 101259013
RN  - 0 (Adaptor Proteins, Signal Transducing)
RN  - 0 (Phosphoproteins)
RN  - 0 (Photosensitizing Agents)
RN  - 0 (Porphyrins)
RN  - 0 (Transcription Factors)
RN  - 0 (YAP-Signaling Proteins)
RN  - 0 (YAP1 protein, human)
RN  - 0X9PA28K43 (Verteporfin)
RN  - EC 2.3.- (Acyltransferases)
RN  - EC 2.3.1.- (TAFAZZIN protein, human)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
SB  - IM
MH  - Acyltransferases
MH  - Adaptor Proteins, Signal Transducing/*antagonists & inhibitors
MH  - Cell Line, Tumor
MH  - Hippo Signaling Pathway
MH  - Humans
MH  - Molecular Structure
MH  - Phosphoproteins/*antagonists & inhibitors
MH  - Photosensitizing Agents/chemical synthesis/chemistry/*pharmacology
MH  - Porphyrins/*chemical synthesis/chemistry/*pharmacology
MH  - Protein Serine-Threonine Kinases/*metabolism
MH  - Signal Transduction/*drug effects
MH  - Structure-Activity Relationship
MH  - Transcription Factors/*antagonists & inhibitors
MH  - Verteporfin
MH  - YAP-Signaling Proteins
OTO - NOTNLM
OT  - Hippo pathway
OT  - cancer
OT  - dipyrrins
OT  - non-photoinduced therapy
OT  - verteporfin
EDAT- 2017/03/24 06:00
MHDA- 2017/09/30 06:00
CRDT- 2017/03/24 06:00
PHST- 2017/01/30 00:00 [received]
PHST- 2017/03/17 00:00 [revised]
PHST- 2017/03/24 06:00 [pubmed]
PHST- 2017/09/30 06:00 [medline]
PHST- 2017/03/24 06:00 [entrez]
AID - 10.1002/cmdc.201700063 [doi]
PST - ppublish
SO  - ChemMedChem. 2017 Jun 21;12(12):954-961. doi: 10.1002/cmdc.201700063. Epub 2017 
      Apr 20.