product name YM201636
Description: YM201636 is a selective PIKfyve inhibitor with IC50 of 33 nM, it is less potent to p110α and insensitive to Fabl (yeast orthologue). The pyridofuropyrimidine compound, YM201636, is a small-molecule inhibitor of PIKfyve. In the in vitro assay, it inhibits PIKfyve with IC50 value of 33nM and shows no inhibition of yeast orthologue of PIKfyve. It inhibits PtdIns3P p110α and type Iα PtdInsP kinase with IC50 values of 3μM and > 2μM, respectively. The type IIγ PtdInsP kinase is found to be insensitive to YM201636. In serum-starved NIH3T3 cells, YM201636 inhibits PtdIns (3, 5) P2 production by 80% at concentration of 800nM.
References: EMBO Rep. 2008 Feb;9(2):164-70; Biochem Biophys Res Commun. 2009 May 8;382(3):566-70.
467.48
Formula
C25H21N7O3
CAS No.
371942-69-7
Storage
-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)
DMSO: 35 mg/mL (74.9 mM)
Water: <1 mg/mL
Ethanol: <1 mg/mL
Solubility (In vivo)
Chemical Name
6-amino-N-[3-(4-morpholin-4-ylpyrido[2,3]furo[2,4-b]pyrimidin-2-yl)phenyl]pyridine-3-carboxamide
other peoduct :
| In Vitro |
In vitro: YM201636 is a selective PIKfyve inhibitor with IC50 of 33 nM, less potent to p110α and insensitive to Fabl (yeast orthologue). Kinase Assay: The assay is performed in kinase buffer (25 mM HEPES pH 7.4, 120 mM NaCl, 1.5 mM MgCl2, 5 mM 2-glycerophosphate, and 1 mM DTT) containing 100 μM PI(3)P, GST-PIKfyve, 50 μM ATP/10 μCi [32P]γATP and increasing concentrations of YM201636 in a final volume of 65 μL. The reactions are incubated for 15 minutes at 30 °C, and stopped by the addition of 243 μL of 2:1 MeOH : CHCl3 (volume : volume). Lipid products labelled with 32P are analysed by thin-layer chromatography and quantified by Cerenkov counting. IC50 value is determined by using Graphpad Prism and errors are given as ±95% confidence limit. Cell Assay: YM201636 potently inhibits mammalian PIKfyve with an IC50 of 33 nM but not yeast orthologue Fab1 with an IC50 of >5 μM, exhibiting around 100-fold selectivity for PtdIns3P p110α with an IC50 of 3 μM. YM201636 (0.8 μM) significantly decreases the production of PtdIns(3,5)P2 by 80% in serum-starved NIH3T3 cells followed by serum stimulation with no effect on serum-stimulated protein kinase B (PKB) Ser 473 phosphorylation. YM-201636 reversibly impairs endosomal trafficking in NIH3T3 cells by blocking PIKfyve and PtdIns(3,5)P2 production, mimicking the effect produced by depleting PIKfyve with siRNA. YM-201636 (0.8 μM) also significantly reduces retroviruses budding from cells by 80%, apparently through interfering with the endosomal sorting complex required for transport (ESCRT) machinery. In 3T3L1 adipocytes, YM-201636 inhibits basal and insulin-activated 2-deoxyglucose uptake with an IC50 of 54 nM, with almost complete inhibition at doses as low as 160 nM. YM-201636 (0.1 μM) has also been shown to completely block insulin-dependent activation of class IA PI 3-kinase. Although not involved in NPM-ALK-dependent proliferation and migration, YM201636 (0.4 μM) strongly reduces invasive capacities of NPM-ALK-expressing cells and their capacity to degrade the extracellular matrix. YM201636 treatment blocks the continuous recycling of junctional proteins claudin-1 and claudin-2 in MDCK cells, leading to the intracellular accumulation and delay of epithelial barrier formation. |
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| References | [1] Jefferies HB, et al. EMBO Rep, 2008, 9(2), 164-170. |
