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
PubMed ID:
32551019
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
Journals
|
1
2
3
4
5
6
|
|
|
Journal of Medicinal Chemistry
6 publications, 12%
|
|
|
ACS Chemical Biology
3 publications, 6%
|
|
|
Nature Chemical Biology
2 publications, 4%
|
|
|
Bioorganic and Medicinal Chemistry Letters
2 publications, 4%
|
|
|
Nature Communications
2 publications, 4%
|
|
|
European Journal of Medicinal Chemistry
2 publications, 4%
|
|
|
Journal of Chemical Information and Modeling
2 publications, 4%
|
|
|
ACS Medicinal Chemistry Letters
2 publications, 4%
|
|
|
JACS Au
2 publications, 4%
|
|
|
Cancers
1 publication, 2%
|
|
|
Oncogenesis
1 publication, 2%
|
|
|
Current Opinion in Chemical Biology
1 publication, 2%
|
|
|
PLoS ONE
1 publication, 2%
|
|
|
Cell Chemical Biology
1 publication, 2%
|
|
|
Molecular Oncology
1 publication, 2%
|
|
|
Bioorganic Chemistry
1 publication, 2%
|
|
|
Neuro-Oncology
1 publication, 2%
|
|
|
European Journal of Organic Chemistry
1 publication, 2%
|
|
|
Journal of the American Chemical Society
1 publication, 2%
|
|
|
Journal of Biomolecular Structure and Dynamics
1 publication, 2%
|
|
|
Saudi Pharmaceutical Journal
1 publication, 2%
|
|
|
Trends in Pharmacological Sciences
1 publication, 2%
|
|
|
Frontiers in Oncology
1 publication, 2%
|
|
|
Bioconjugate Chemistry
1 publication, 2%
|
|
|
Cancer Letters
1 publication, 2%
|
|
|
Current Pharmaceutical Design
1 publication, 2%
|
|
|
1
2
3
4
5
6
|
Publishers
|
2
4
6
8
10
12
14
16
18
|
|
|
American Chemical Society (ACS)
17 publications, 34%
|
|
|
Elsevier
11 publications, 22%
|
|
|
Cold Spring Harbor Laboratory
8 publications, 16%
|
|
|
Springer Nature
5 publications, 10%
|
|
|
Wiley
2 publications, 4%
|
|
|
MDPI
1 publication, 2%
|
|
|
Public Library of Science (PLoS)
1 publication, 2%
|
|
|
Oxford University Press
1 publication, 2%
|
|
|
Taylor & Francis
1 publication, 2%
|
|
|
Frontiers Media S.A.
1 publication, 2%
|
|
|
Bentham Science Publishers Ltd.
1 publication, 2%
|
|
|
Royal Society of Chemistry (RSC)
1 publication, 2%
|
|
|
2
4
6
8
10
12
14
16
18
|
- 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.
Are you a researcher?
Create a profile to get free access to personal recommendations for colleagues and new articles.
Metrics
Cite this
GOST |
RIS |
BibTex |
MLA
Cite this
GOST
Copy
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.
GOST all authors (up to 50)
Copy
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.
Cite this
RIS
Copy
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
PB - American Chemical Society (ACS)
SP - 1324-1329
IS - 6
VL - 11
PMID - 32551019
SN - 1948-5875
ER -
Cite this
BibTex
Copy
@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.