ACS Medicinal Chemistry Letters, volume 11, issue 6, pages 1324-1329
Discovery of CPI-1612: A Potent, Selective, and Orally Bioavailable EP300/CBP Histone Acetyltransferase Inhibitor
Jonathan Wilson
1
,
Gaurav Patel
2
,
Chirag Patel
2
,
Francois Brucelle
1
,
Annissa J. Huhn
1
,
Anna Gardberg
1
,
Florence Poy
1
,
Nico Cantone
1
,
Archana Bommi Reddy
1
,
Robert J. Sims
1
,
Richard T Cummings
1
,
Julian Levell
1
1
Constellation Pharmaceuticals, 215 First Street, Suite 200, Cambridge, Massachusetts 02142, United States
|
2
Piramal Enterprises Limited-Discovery Solutions, Ahmedabad, Gujarat 382 213, India
|
Publication type: Journal Article
Publication date: 2020-04-23
Journal:
ACS Medicinal Chemistry Letters
Quartile SCImago
Q1
Quartile WOS
Q2
Impact factor: 4.2
ISSN: 19485875, 19485875
Organic Chemistry
Drug Discovery
Biochemistry
Abstract
The histone acetyltransferases, CREB binding protein (CBP) and EP300, are master transcriptional co-regulators that have been implicated in numerous diseases, such as cancer, inflammatory disorders, and neurodegeneration. A novel, highly potent, orally bioavailable EP300/CBP histone acetyltransferase (HAT) inhibitor, CPI-1612 or 17, was developed from the lead compound 3. Replacement of the indole scaffold of 3 with the aminopyridine scaffold of 17 led to improvements in potency, solubility, and bioavailability. These characteristics resulted in a 20-fold lower efficacious dose for 17 relative to lead 3 in a JEKO-1 tumor mouse xenograft study.
Top-30
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1 publication, 2.13%
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1 publication, 2.13%
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1 publication, 2.13%
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1 publication, 2.13%
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1 publication, 2.13%
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1 publication, 2.13%
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1 publication, 2.13%
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1 publication, 2.13%
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1 publication, 2.13%
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1 publication, 2.13%
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1 publication, 2.13%
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Citations by publishers
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American Chemical Society (ACS)
17 publications, 36.17%
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Elsevier
9 publications, 19.15%
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Springer Nature
5 publications, 10.64%
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Wiley
2 publications, 4.26%
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Multidisciplinary Digital Publishing Institute (MDPI)
1 publication, 2.13%
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Public Library of Science (PLoS)
1 publication, 2.13%
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Oxford University Press
1 publication, 2.13%
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Taylor & Francis
1 publication, 2.13%
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Cold Spring Harbor Laboratory
1 publication, 2.13%
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Frontiers Media S.A.
1 publication, 2.13%
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- We do not take into account publications without a DOI.
- Statistics recalculated only for publications connected to researchers, organizations and labs registered on the platform.
- Statistics recalculated weekly.
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Wilson J. et al. Discovery of CPI-1612: A Potent, Selective, and Orally Bioavailable EP300/CBP Histone Acetyltransferase Inhibitor // ACS Medicinal Chemistry Letters. 2020. Vol. 11. No. 6. pp. 1324-1329.
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Wilson J., Patel G., Patel C., Brucelle F., Huhn A. J., Gardberg A., Poy F., Cantone N., Bommi Reddy A., Sims R. J., Cummings R. T., Levell J. Discovery of CPI-1612: A Potent, Selective, and Orally Bioavailable EP300/CBP Histone Acetyltransferase Inhibitor // ACS Medicinal Chemistry Letters. 2020. Vol. 11. No. 6. pp. 1324-1329.
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RIS
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TY - JOUR
DO - 10.1021/acsmedchemlett.0c00155
UR - https://doi.org/10.1021/acsmedchemlett.0c00155
TI - Discovery of CPI-1612: A Potent, Selective, and Orally Bioavailable EP300/CBP Histone Acetyltransferase Inhibitor
T2 - ACS Medicinal Chemistry Letters
AU - Patel, Gaurav
AU - Patel, Chirag
AU - Brucelle, Francois
AU - Poy, Florence
AU - Cantone, Nico
AU - Bommi Reddy, Archana
AU - Sims, Robert J.
AU - Wilson, Jonathan
AU - Levell, Julian
AU - Huhn, Annissa J.
AU - Gardberg, Anna
AU - Cummings, Richard T
PY - 2020
DA - 2020/04/23 00:00:00
PB - American Chemical Society (ACS)
SP - 1324-1329
IS - 6
VL - 11
SN - 1948-5875
SN - 1948-5875
ER -
Cite this
BibTex
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@article{2020_Wilson,
author = {Gaurav Patel and Chirag Patel and Francois Brucelle and Florence Poy and Nico Cantone and Archana Bommi Reddy and Robert J. Sims and Jonathan Wilson and Julian Levell and Annissa J. Huhn and Anna Gardberg and Richard T Cummings},
title = {Discovery of CPI-1612: A Potent, Selective, and Orally Bioavailable EP300/CBP Histone Acetyltransferase Inhibitor},
journal = {ACS Medicinal Chemistry Letters},
year = {2020},
volume = {11},
publisher = {American Chemical Society (ACS)},
month = {apr},
url = {https://doi.org/10.1021/acsmedchemlett.0c00155},
number = {6},
pages = {1324--1329},
doi = {10.1021/acsmedchemlett.0c00155}
}
Cite this
MLA
Copy
Wilson, Jonathan, et al. “Discovery of CPI-1612: A Potent, Selective, and Orally Bioavailable EP300/CBP Histone Acetyltransferase Inhibitor.” ACS Medicinal Chemistry Letters, vol. 11, no. 6, Apr. 2020, pp. 1324-1329. https://doi.org/10.1021/acsmedchemlett.0c00155.