2007
DOI: 10.1158/0008-5472.can-07-1826
|View full text |Cite
|
Sign up to set email alerts
|

Meriolins, a New Class of Cell Death–Inducing Kinase Inhibitors with Enhanced Selectivity for Cyclin-Dependent Kinases

Abstract: Protein kinases represent promising anticancer drug targets. We describe here the meriolins, a new family of inhibitors of cyclin-dependent kinases (CDK). Meriolins represent a chemical structural hybrid between meridianins and variolins, two families of kinase inhibitors extracted from various marine invertebrates. Variolin B is currently in preclinical evaluation as an antitumor agent. A selectivity study done on 32 kinases showed that, compared with variolin B, meriolins display enhanced specificity toward … Show more

Help me understand this report
View preprint versions

Search citation statements

Order By: Relevance

Paper Sections

Select...
3
1
1

Citation Types

3
149
0

Year Published

2008
2008
2022
2022

Publication Types

Select...
4
3

Relationship

1
6

Authors

Journals

citations
Cited by 104 publications
(152 citation statements)
references
References 49 publications
3
149
0
Order By: Relevance
“…CDK1/cyclin B (M-phase starfish oocytes, native), CDK2/ cyclin A, CDK2/cyclin E, CDK5/p25, and CDK7/cyclin H (human, recombinant) were prepared as described previously (44). Their kinase activity was assayed in buffer C, with 1 mg histone H1/mL, in the presence of 15 Amol/L [g- 33 P]ATP (3,000 Ci/mmol; 10 mCi/mL) in a final volume of 30 AL.…”
Section: Methodsmentioning
confidence: 99%
“…CDK1/cyclin B (M-phase starfish oocytes, native), CDK2/ cyclin A, CDK2/cyclin E, CDK5/p25, and CDK7/cyclin H (human, recombinant) were prepared as described previously (44). Their kinase activity was assayed in buffer C, with 1 mg histone H1/mL, in the presence of 15 Amol/L [g- 33 P]ATP (3,000 Ci/mmol; 10 mCi/mL) in a final volume of 30 AL.…”
Section: Methodsmentioning
confidence: 99%
“…However, the inhibition of CDK9 (IC50 26 nM) was determined to be even more potent than that of either CDK1 (IC50 60 nM) or CDK2 (IC50 80 nM). Strong inhibition by variolin B of several other kinases was observed, including casein kinase-1 (CK1), FMS-like tyrosine kinase 3, and glycogen synthase kinase-3 (GSK3) [7,8]. The unique heterocyclic framework of variolin thus emerged as a new scaffold for the design of new inhibitors of CDKs.…”
Section: β-Pyridopyrrolopyrimidine Alkaloids: Variolins a New Familymentioning
confidence: 99%
“…A new class of 7-azaindole-containing analogues have been thus designed and the term "meriolin" has been coined to describe this hybrid structure ( Figure 4) [7,8]. Meriolins (22)(23)(24)(25) display potent inhibitory activity and relative selectivity toward CDKs and also exhibit better antiproliferative and proapoptotic properties in cell cultures than their ''inspirational parent'' molecules.…”
Section: β-Pyridopyrrolopyrimidine Alkaloids: Variolins a New Familymentioning
confidence: 99%
See 2 more Smart Citations