Target nature :
Multitarget inhibitor of Cyclin-Dependent Kinases (CDKs)
CAS n° :
Mecanism of action :
A cell-permeable, ATP site (Type I)-targeting azaindolopyrimidine compound that is reported to inhibit kinase activity.
Physico-chemical properties :
OK to freeze (protect from light)
Solubility in DMSO: 50mg/mL
Index of Refraction: 1.719
Molar Refractivity: 68.3±0.3 cm3
Density: 1.4±0.1 g/cm3
Probe availability :
Commercial (ex. Calbiochem product number 445821)
Princeps reference :
Bettayeb K. et al. 2007. Meriolins, a new class of cell death inducing kinase inhibitors with enhanced selectivity for cyclin-dependent kinases. Cancer Res. 2007 Sep 1;67(17):8325-34.
More bibliography :
Echalier, A. et al. 2008. J. Med. Chem.51, 737.
Jarry M. et al. 2014. Neuro Oncol. 2014 Nov;16(11):1484-98.
Drießen D. et al. 2019. Bioorg Med Chem. 2019 Aug 1;27(15):3463-3468.
Other available information on the probe :
Synthetic derivatives from molecules initially isolated from various marine invertebrates. New CDK inhibitory scaffold, with promising antitumor activity.
This probes is a member of a serie of derivatives including (R is the methoxy group in Meriolin 3): Meriolin 1: R=H, Meriolin 2: R=OH, Meriolin 3: R=OMe, Meriolin 4: R= OEt)
Other information on the target :
Cyclin-dependent kinases (CDKs) are critical regulatory enzymes that drive all cell cycle transitions, and their activity is under stringent control to ensure successful cell division.
Selectivity profile :
Meriolin 3 inhibits the kinase activity of CDK9/cyclin T, CDK2/cyclin A, CDK1/cyclin B, CDK5/p25 (IC50 = 6, 11, 170, 170 nM, respectively), DYRK1A, CKIdelta/epsilon, GSK-3alpha/ß (IC50 = 29, 200, and 230 nM, respectively), as well as CDK3/cyclin E, CDK4/cyclin D1, CDK6/cyclin D1, CDK7/cyclin H, and FLT3 (IC50<400 nM), while showing much reduced activity agasint 21 other kinases (IC50 >1 µM).
In vivo data :
Shown to effectively retard LS174T-derived tumor growth in mice in vivo (1 to 5 mg/kg/day, i.p.)
Meriolin 3 potently inhibits tumor growth in two mouse xenograft cancer models, namely, Ewing's sarcoma and LS174T colorectal carcinoma [Cancer Res 2007;67(17):8325-34].
In vitro data :
Shown to effectively inhibit cellular CDK substrates phosphorylation and induce apoptosis in SH-SY5Y neuroblastoma cultures (Effective conc. 0.3 to 1 µM) in vitro. Cell viability tests reveal that Meriolin 3 selectively affects the viability of a panel of 8 cancer lines (IC50<380 nM) in comparison to normal human foreskin fibroblasts (IC50 = 8 µM)
Meriolin 3 was tested at various concentrations for its effects on nine different cell lines. Cell survival was estimated 48 h after the addition of meriolin 3 using the MTS reduction assay. IC50 values (average of triplicate values) are reported in micromoles per liter.
Cell survival (IC50, ¿mol/L; MTS reduction)
LS 174T (colorectal adenocarcinoma) 0.13
HCT116 (colon) 0.94
KMS-11 (myeloma) 0.12
GBM (glioma) 0.14
Huh7 (hepatoma) 0.12
F1 (hepatoma) 0.26
SH-SY5Y (neuroblastoma) 0.072
HEK293 (embryon kidney) 0.38
Human foreskin fibroblasts 8.00
Respiratory protection required when dusts are generated (Recommended Filter type: Filter type P1)
Full contact: Material: Nitrile rubber Minimum layer thickness: 0,11 mm Break through time: 480 min
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