fr | en

meriolin 3

Target nature : Multitarget inhibitor of Cyclin-Dependent Kinases (CDKs)
CAS n° : 954143-48-7
Mecanism of action : A cell-permeable, ATP site (Type I)-targeting azaindolopyrimidine compound that is reported to inhibit kinase activity.
Physico-chemical properties : MW=241.25g/mol OK to freeze (protect from light) Solubility in DMSO: 50mg/mL Index of Refraction: 1.719 Molar Refractivity: 68.3±0.3 cm3 ACD/LogP: 1.55 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) Cell line 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
Toxicity : 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
Chaine SMILES : COc2ccnc3[nH]cc(c1ccnc(N)n1)c23
Contacter l'auteur de la sonde