Standard
Discovery of 2-[1-(4,4-Difluorocyclohexyl)piperidin-4-yl]-6-fluoro-3-oxo-2,3-dihydro-1H-isoindole-4-carboxamide (NMS-P118): A Potent, Orally Available, and Highly Selective PARP-1 Inhibitor for Cancer Therapy. / Papeo, G.; Posteri, H.; Borghi, D.; Busel, A.A.; Caprera, F.; Casale, E.; Ciomei, M.; Cirla, A.; Corti, E.; D'Anello, M.; Fasolini, M.; Forte, B.; Galvani, A.; Isacchi, A.; Khvat, A.; Krasavin, M.Y.; Lupi, R.; Orsini, P.; Perego, R.; Pesenti, E.; Pezzetta, D.; Rainoldi, S.; Riccardi-Sirtori, F.; Scolaro, A.; Sola, F.; Zuccotto, F.; Felder, E.R.; Donati, D.; Montagnoli, A.
In:
Journal of Medicinal Chemistry, No. 17, 2015, p. 6875-6898.
Research output: Contribution to journal › Article
Harvard
Papeo, G, Posteri, H, Borghi, D, Busel, AA, Caprera, F, Casale, E, Ciomei, M, Cirla, A, Corti, E, D'Anello, M, Fasolini, M, Forte, B, Galvani, A, Isacchi, A, Khvat, A
, Krasavin, MY, Lupi, R, Orsini, P, Perego, R, Pesenti, E, Pezzetta, D, Rainoldi, S, Riccardi-Sirtori, F, Scolaro, A, Sola, F, Zuccotto, F, Felder, ER, Donati, D & Montagnoli, A 2015, '
Discovery of 2-[1-(4,4-Difluorocyclohexyl)piperidin-4-yl]-6-fluoro-3-oxo-2,3-dihydro-1H-isoindole-4-carboxamide (NMS-P118): A Potent, Orally Available, and Highly Selective PARP-1 Inhibitor for Cancer Therapy',
Journal of Medicinal Chemistry, no. 17, pp. 6875-6898.
https://doi.org/10.1021/acs.jmedchem.5b00680APA
Papeo, G., Posteri, H., Borghi, D., Busel, A. A., Caprera, F., Casale, E., Ciomei, M., Cirla, A., Corti, E., D'Anello, M., Fasolini, M., Forte, B., Galvani, A., Isacchi, A., Khvat, A.
, Krasavin, M. Y., Lupi, R., Orsini, P., Perego, R., ... Montagnoli, A. (2015).
Discovery of 2-[1-(4,4-Difluorocyclohexyl)piperidin-4-yl]-6-fluoro-3-oxo-2,3-dihydro-1H-isoindole-4-carboxamide (NMS-P118): A Potent, Orally Available, and Highly Selective PARP-1 Inhibitor for Cancer Therapy.
Journal of Medicinal Chemistry, (17), 6875-6898.
https://doi.org/10.1021/acs.jmedchem.5b00680Vancouver
Author
Papeo, G. ; Posteri, H. ; Borghi, D. ; Busel, A.A. ; Caprera, F. ; Casale, E. ; Ciomei, M. ; Cirla, A. ; Corti, E. ; D'Anello, M. ; Fasolini, M. ; Forte, B. ; Galvani, A. ; Isacchi, A. ; Khvat, A.
; Krasavin, M.Y. ; Lupi, R. ; Orsini, P. ; Perego, R. ; Pesenti, E. ; Pezzetta, D. ; Rainoldi, S. ; Riccardi-Sirtori, F. ; Scolaro, A. ; Sola, F. ; Zuccotto, F. ; Felder, E.R. ; Donati, D. ; Montagnoli, A. /
Discovery of 2-[1-(4,4-Difluorocyclohexyl)piperidin-4-yl]-6-fluoro-3-oxo-2,3-dihydro-1H-isoindole-4-carboxamide (NMS-P118): A Potent, Orally Available, and Highly Selective PARP-1 Inhibitor for Cancer Therapy. In:
Journal of Medicinal Chemistry. 2015 ; No. 17. pp. 6875-6898.
BibTeX
@article{ef9601ae76354e71b84f4d3087fdeffd,
title = "Discovery of 2-[1-(4,4-Difluorocyclohexyl)piperidin-4-yl]-6-fluoro-3-oxo-2,3-dihydro-1H-isoindole-4-carboxamide (NMS-P118): A Potent, Orally Available, and Highly Selective PARP-1 Inhibitor for Cancer Therapy",
abstract = "{\textcopyright} 2015 American Chemical Society.The nuclear protein poly(ADP-ribose) polymerase-1 (PARP-1) has a well-established role in the signaling and repair of DNA and is a prominent target in oncology, as testified by the number of candidates in clinical testing that unselectively target both PARP-1 and its closest isoform PARP-2. The goal of our program was to find a PARP-1 selective inhibitor that would potentially mitigate toxicities arising from cross-inhibition of PARP-2. Thus, an HTS campaign on the proprietary Nerviano Medical Sciences (NMS) chemical collection, followed by SAR optimization, allowed us to discover 2-[1-(4,4-difluorocyclohexyl)piperidin-4-yl]-6-fluoro-3-oxo-2,3-dihydro-1H-isoindole-4-carboxamide (NMS-P118, 20by). NMS-P118 proved to be a potent, orally available, and highly selective PARP-1 inhibitor endowed with excellent ADME and pharmacokinetic profiles and high efficacy in vivo both as a single agent and in combination with Temozolomide in MDA-MB-436 and Capan-1 xenograft models, respectivel",
author = "G. Papeo and H. Posteri and D. Borghi and A.A. Busel and F. Caprera and E. Casale and M. Ciomei and A. Cirla and E. Corti and M. D'Anello and M. Fasolini and B. Forte and A. Galvani and A. Isacchi and A. Khvat and M.Y. Krasavin and R. Lupi and P. Orsini and R. Perego and E. Pesenti and D. Pezzetta and S. Rainoldi and F. Riccardi-Sirtori and A. Scolaro and F. Sola and F. Zuccotto and E.R. Felder and D. Donati and A. Montagnoli",
year = "2015",
doi = "10.1021/acs.jmedchem.5b00680",
language = "English",
pages = "6875--6898",
journal = "Journal of Medicinal Chemistry",
issn = "0022-2623",
publisher = "American Chemical Society",
number = "17",
}
RIS
TY - JOUR
T1 - Discovery of 2-[1-(4,4-Difluorocyclohexyl)piperidin-4-yl]-6-fluoro-3-oxo-2,3-dihydro-1H-isoindole-4-carboxamide (NMS-P118): A Potent, Orally Available, and Highly Selective PARP-1 Inhibitor for Cancer Therapy
AU - Papeo, G.
AU - Posteri, H.
AU - Borghi, D.
AU - Busel, A.A.
AU - Caprera, F.
AU - Casale, E.
AU - Ciomei, M.
AU - Cirla, A.
AU - Corti, E.
AU - D'Anello, M.
AU - Fasolini, M.
AU - Forte, B.
AU - Galvani, A.
AU - Isacchi, A.
AU - Khvat, A.
AU - Krasavin, M.Y.
AU - Lupi, R.
AU - Orsini, P.
AU - Perego, R.
AU - Pesenti, E.
AU - Pezzetta, D.
AU - Rainoldi, S.
AU - Riccardi-Sirtori, F.
AU - Scolaro, A.
AU - Sola, F.
AU - Zuccotto, F.
AU - Felder, E.R.
AU - Donati, D.
AU - Montagnoli, A.
PY - 2015
Y1 - 2015
N2 - © 2015 American Chemical Society.The nuclear protein poly(ADP-ribose) polymerase-1 (PARP-1) has a well-established role in the signaling and repair of DNA and is a prominent target in oncology, as testified by the number of candidates in clinical testing that unselectively target both PARP-1 and its closest isoform PARP-2. The goal of our program was to find a PARP-1 selective inhibitor that would potentially mitigate toxicities arising from cross-inhibition of PARP-2. Thus, an HTS campaign on the proprietary Nerviano Medical Sciences (NMS) chemical collection, followed by SAR optimization, allowed us to discover 2-[1-(4,4-difluorocyclohexyl)piperidin-4-yl]-6-fluoro-3-oxo-2,3-dihydro-1H-isoindole-4-carboxamide (NMS-P118, 20by). NMS-P118 proved to be a potent, orally available, and highly selective PARP-1 inhibitor endowed with excellent ADME and pharmacokinetic profiles and high efficacy in vivo both as a single agent and in combination with Temozolomide in MDA-MB-436 and Capan-1 xenograft models, respectivel
AB - © 2015 American Chemical Society.The nuclear protein poly(ADP-ribose) polymerase-1 (PARP-1) has a well-established role in the signaling and repair of DNA and is a prominent target in oncology, as testified by the number of candidates in clinical testing that unselectively target both PARP-1 and its closest isoform PARP-2. The goal of our program was to find a PARP-1 selective inhibitor that would potentially mitigate toxicities arising from cross-inhibition of PARP-2. Thus, an HTS campaign on the proprietary Nerviano Medical Sciences (NMS) chemical collection, followed by SAR optimization, allowed us to discover 2-[1-(4,4-difluorocyclohexyl)piperidin-4-yl]-6-fluoro-3-oxo-2,3-dihydro-1H-isoindole-4-carboxamide (NMS-P118, 20by). NMS-P118 proved to be a potent, orally available, and highly selective PARP-1 inhibitor endowed with excellent ADME and pharmacokinetic profiles and high efficacy in vivo both as a single agent and in combination with Temozolomide in MDA-MB-436 and Capan-1 xenograft models, respectivel
U2 - 10.1021/acs.jmedchem.5b00680
DO - 10.1021/acs.jmedchem.5b00680
M3 - Article
SP - 6875
EP - 6898
JO - Journal of Medicinal Chemistry
JF - Journal of Medicinal Chemistry
SN - 0022-2623
IS - 17
ER -
