PMID- 37197453
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20240512
IS  - 1948-5875 (Print)
IS  - 1948-5875 (Electronic)
IS  - 1948-5875 (Linking)
VI  - 14
IP  - 5
DP  - 2023 May 11
TI  - Discovery of a Novel Series of Potent SHP2 Allosteric Inhibitors.
PG  - 645-651
LID - 10.1021/acsmedchemlett.3c00059 [doi]
AB  - Src homology 2-containing protein tyrosine phosphatase 2 (SHP2) is the first 
      reported nonreceptor oncogenic tyrosine phosphatase connecting multiple signal 
      transduction cascades and exerting immunoinhibitory function through the PD-1 
      checkpoint receptor. As part of a drug discovery program aimed at obtaining novel 
      allosteric SHP2 inhibitors, a series of pyrazopyrazine derivatives bearing an 
      original bicyclo[3.1.0]hexane basic moiety on the left-hand side region of the 
      molecule were identified. We report herein the discovery process, the in vitro 
      pharmacological profile, and the early developability features of compound 25, 
      one of the most potent members of the series.
CI  - (c) 2023 American Chemical Society.
FAU - Petrocchi, Alessia
AU  - Petrocchi A
AD  - IRBM S.p.A, Via Pontina Km 30.600, 00070 Pomezia, Italy.
FAU - Grillo, Alessandro
AU  - Grillo A
AD  - Promidis, Via Olgettina 60, 20132 Milano, Italy.
FAU - Ferrante, Luca
AU  - Ferrante L
AD  - Promidis, Via Olgettina 60, 20132 Milano, Italy.
FAU - Randazzo, Pietro
AU  - Randazzo P
AD  - Promidis, Via Olgettina 60, 20132 Milano, Italy.
FAU - Prandi, Adolfo
AU  - Prandi A
AD  - Promidis, Via Olgettina 60, 20132 Milano, Italy.
FAU - De Matteo, Marilenia
AU  - De Matteo M
AD  - Promidis, Via Olgettina 60, 20132 Milano, Italy.
FAU - Iaccarino, Costanza
AU  - Iaccarino C
AD  - IRBM S.p.A, Via Pontina Km 30.600, 00070 Pomezia, Italy.
FAU - Bisbocci, Monica
AU  - Bisbocci M
AD  - IRBM S.p.A, Via Pontina Km 30.600, 00070 Pomezia, Italy.
FAU - Cellucci, Antonella
AU  - Cellucci A
AD  - IRBM S.p.A, Via Pontina Km 30.600, 00070 Pomezia, Italy.
FAU - Alli, Cristina
AU  - Alli C
AD  - IRBM S.p.A, Via Pontina Km 30.600, 00070 Pomezia, Italy.
FAU - Nibbio, Martina
AU  - Nibbio M
AD  - IRBM S.p.A, Via Pontina Km 30.600, 00070 Pomezia, Italy.
FAU - Pucci, Vincenzo
AU  - Pucci V
AD  - IRBM S.p.A, Via Pontina Km 30.600, 00070 Pomezia, Italy.
FAU - Amaudrut, Jerome
AU  - Amaudrut J
AUID- ORCID: 0000-0003-0498-4089
AD  - IRBM S.p.A, Via Pontina Km 30.600, 00070 Pomezia, Italy.
FAU - Montalbetti, Christian
AU  - Montalbetti C
AD  - IRBM S.p.A, Via Pontina Km 30.600, 00070 Pomezia, Italy.
FAU - Toniatti, Carlo
AU  - Toniatti C
AD  - IRBM S.p.A, Via Pontina Km 30.600, 00070 Pomezia, Italy.
FAU - Di Fabio, Romano
AU  - Di Fabio R
AUID- ORCID: 0000-0002-5818-6544
AD  - IRBM S.p.A, Via Pontina Km 30.600, 00070 Pomezia, Italy.
AD  - Promidis, Via Olgettina 60, 20132 Milano, Italy.
LA  - eng
PT  - Journal Article
DEP - 20230417
PL  - United States
TA  - ACS Med Chem Lett
JT  - ACS medicinal chemistry letters
JID - 101521073
PMC - PMC10184159
COIS- The authors declare no competing financial interest.
EDAT- 2023/05/18 01:07
MHDA- 2023/05/18 01:08
PMCR- 2024/05/11
CRDT- 2023/05/17 20:02
PHST- 2023/02/21 00:00 [received]
PHST- 2023/04/10 00:00 [accepted]
PHST- 2023/05/18 01:08 [medline]
PHST- 2023/05/18 01:07 [pubmed]
PHST- 2023/05/17 20:02 [entrez]
PHST- 2024/05/11 00:00 [pmc-release]
AID - 10.1021/acsmedchemlett.3c00059 [doi]
PST - epublish
SO  - ACS Med Chem Lett. 2023 Apr 17;14(5):645-651. doi: 
      10.1021/acsmedchemlett.3c00059. eCollection 2023 May 11.