Synthetic Optimization and MAPK Pathway Activation Anticancer Mechanism of Polyisoprenylated Cysteinyl Amide Inhibitors.
ERK1/2
KRAS
MAPK
MEK1/2
PCAIs
p90RSK
Journal
Cancers
ISSN: 2072-6694
Titre abrégé: Cancers (Basel)
Pays: Switzerland
ID NLM: 101526829
Informations de publication
Date de publication:
17 Nov 2021
17 Nov 2021
Historique:
received:
18
10
2021
revised:
14
11
2021
accepted:
15
11
2021
entrez:
27
11
2021
pubmed:
28
11
2021
medline:
28
11
2021
Statut:
epublish
Résumé
Abnormalities of the MAPK pathway play vital roles in cancer initiation and progression. RAS GTPases that are key upstream mediators of the pathway are mutated in 30% of human cancers. Polyisoprenylated cysteinyl amide inhibitors (PCAIs) were designed as potential targeted therapies against the RAS-driven cancers. The current study reports on the optimization of the PCAIs and the determination of their mechanisms of action in KRAS-mutant cancer cells. They display ClogP values ranging from 3.01 to 6.35, suppressing the viabilities of KRAS-mutant MDA-MB-231, A549, MIA PaCa-2, and NCI-H1299 cells in 2D and 3D cultures with EC
Identifiants
pubmed: 34830912
pii: cancers13225757
doi: 10.3390/cancers13225757
pmc: PMC8616522
pii:
doi:
Types de publication
Journal Article
Langues
eng
Subventions
Organisme : NCI NIH HHS
ID : SC1 CA190505
Pays : United States
Organisme : NIMHD NIH HHS
ID : U54 MD007582
Pays : United States
Organisme : NIH HHS
ID : SC1CA190505
Pays : United States
Organisme : NIH HHS
ID : U54 MD007582
Pays : United States
Références
Nat Rev Mol Cell Biol. 2016 Feb;17(2):110-22
pubmed: 26790532
Eur J Med Chem. 2014 Jun 23;81:323-33
pubmed: 24852279
Cell Cycle. 2009 Apr 15;8(8):1168-75
pubmed: 19282669
Nat Rev Drug Discov. 2014 Nov;13(11):828-51
pubmed: 25323927
Front Biosci. 2008 May 01;13:4258-75
pubmed: 18508509
Adv Cancer Res. 1998;74:49-139
pubmed: 9561267
Nat Rev Drug Discov. 2020 Aug;19(8):533-552
pubmed: 32528145
Biochim Biophys Acta. 2007 Aug;1773(8):1177-95
pubmed: 17428555
Proc Natl Acad Sci U S A. 1987 Oct;84(19):6899-903
pubmed: 3477813
Semin Cancer Biol. 2018 Feb;48:53-61
pubmed: 28476656
Oncol Rep. 2015 Jan;33(1):119-24
pubmed: 25394563
J Am Chem Soc. 2012 Jul 18;134(28):11503-10
pubmed: 22721555
Oncotarget. 2017 May 9;8(19):31726-31744
pubmed: 28423648
Mol Cancer Res. 2015 Sep;13(9):1325-35
pubmed: 26037647
Genes Cancer. 2011 Mar;2(3):359-72
pubmed: 21779505
Endocr Rev. 2001 Apr;22(2):153-83
pubmed: 11294822
Cold Spring Harb Perspect Med. 2019 Jan 2;9(1):
pubmed: 29358316
Oncol Lett. 2017 Dec;14(6):6999-7010
pubmed: 29344128
Biochemistry. 1994 Mar 15;33(10):3014-22
pubmed: 8130214
IUBMB Life. 2006 Nov;58(11):621-31
pubmed: 17085381
Biochemistry. 1997 Oct 21;36(42):13102-9
pubmed: 9335573
Oncotarget. 2018 May 25;9(40):25781-25795
pubmed: 29899821
Growth Factors. 2006 Mar;24(1):21-44
pubmed: 16393692
CA Cancer J Clin. 2021 Jan;71(1):7-33
pubmed: 33433946
Proteomics. 2010 Apr;10(8):1716-20
pubmed: 20127689
Nature. 1988 Aug 25;334(6184):715-8
pubmed: 2842685
Nat Rev Mol Cell Biol. 2011 Dec 22;13(1):39-51
pubmed: 22189424
Science. 2004 Jun 4;304(5676):1497-500
pubmed: 15118125
J Biol Chem. 1995 Apr 28;270(17):9809-12
pubmed: 7730360
Cancers (Basel). 2019 Dec 20;12(1):
pubmed: 31861875
FEBS J. 2010 Jan;277(1):2-21
pubmed: 19843174
Trends Biochem Sci. 2006 May;31(5):268-75
pubmed: 16603362
Clin Cancer Res. 1997 Apr;3(4):515-22
pubmed: 9815714
Mol Cancer. 2006 Aug 09;5:31
pubmed: 16899113
J Biol Chem. 2000 Jul 21;275(29):22172-9
pubmed: 10777480
Am J Cancer Res. 2017 Jul 01;7(7):1515-1527
pubmed: 28744401
Curr Cancer Drug Targets. 2019;19(10):838-851
pubmed: 30914025
Microbiol Mol Biol Rev. 2011 Mar;75(1):50-83
pubmed: 21372320
Cell. 2007 Jun 1;129(5):865-77
pubmed: 17540168
Curr Med Chem. 2021;28(18):3476-3489
pubmed: 33176634
Biophys J. 2016 Jul 12;111(1):113-22
pubmed: 27410739
Nature. 2015 Apr 16;520(7547):278-80
pubmed: 25877186
Cancer Res. 2020 Jul 15;80(14):2969-2974
pubmed: 32209560
Pathol Res Pract. 2009;205(12):858-62
pubmed: 19679400
Cancer Res. 2013 Oct 15;73(20):6099-105
pubmed: 24097826