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
Q1
Q2
SJR: 0.883
CiteScore: 7.3
Impact factor: 3.5
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.
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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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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 - Wilson, Jonathan
AU - Patel, Gaurav
AU - Patel, Chirag
AU - Brucelle, Francois
AU - Huhn, Annissa J.
AU - Gardberg, Anna
AU - Poy, Florence
AU - Cantone, Nico
AU - Bommi Reddy, Archana
AU - Sims, Robert J.
AU - Cummings, Richard T
AU - Levell, Julian
PY - 2020
DA - 2020/04/23
PB - American Chemical Society (ACS)
SP - 1324-1329
IS - 6
VL - 11
PMID - 32551019
SN - 1948-5875
ER -
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BibTex (up to 50 authors)
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@article{2020_Wilson,
author = {Jonathan Wilson and Gaurav Patel and Chirag Patel and Francois Brucelle and Annissa J. Huhn and Anna Gardberg and Florence Poy and Nico Cantone and Archana Bommi Reddy and Robert J. Sims and Richard T Cummings and Julian Levell},
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.