YM201636

• CAT Number: I003368
• CAS Number: 371942-69-7
• Molecular Formula: C₂₅H₂₁N₇O₃
• Molecular Weight: 467.49
• Purity: ≥95%
• Target: PIKfyve
• Solubility: DMSO ≥33mg/mL Water <1.2mg/mL Ethanol <1.2mg/mL
• Storage: 3 years -20℃ powder
• IC50: 33 nM [1]
• IUPAC Name: 6-amino-N-[3-(6-morpholin-4-yl-8-oxa-3,5,10-triazatricyclo[7.4.0.02,7]trideca-1(9),2(7),3,5,10,12-hexaen-4-yl)phenyl]pyridine-3-carboxamide
• InChI: InChI=1S/C25H21N7O3/c26-19-7-6-16(14-28-19)24(33)29-17-4-1-3-15(13-17)22-30-20-18-5-2-8-27-25(18)35-21(20)23(31-22)32-9-11-34-12-10-32/h1-8,13-14H,9-12H2,(H2,26,28)(H,29,33)
• InChIKey: YBPIBGNBHHGLEB-UHFFFAOYSA-N
• SMILES: C1COCCN1C2=NC(=NC3=C2OC4=C3C=CC=N4)C5=CC(=CC=C5)NC(=O)C6=CN=C(C=C6)N

YM201636 (Cat.No:I003368) is a selective PIKfyve inhibitor with IC50 of 33 nM, less potent to p110α. 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.

Reference

1:PLoS One. 2013;8(3):e60152. doi: 10.1371/journal.pone.0060152. Epub 2013 Mar 27. Inhibition of PIKfyve by YM-201636 dysregulates autophagy and leads to apoptosis-independent neuronal cell death.Martin S,Harper CB,May LM,Coulson EJ,Meunier FA,Osborne SL, PMID: 23544129 PMCID: PMC3609765 DOI: 10.1371/journal.pone.0060152 Abstract: The lipid phosphatidylinositol 3,5-bisphosphate (PtdIns(3,5)P 2), synthesised by PIKfyve, regulates a number of intracellular membrane trafficking pathways. Genetic alteration of the PIKfyve complex, leading to even a mild reduction in PtdIns(3,5)P 2, results in marked neurodegeneration via an uncharacterised mechanism. In the present study we have shown that selectively inhibiting PIKfyve activity, using YM-201636, significantly reduces the survival of primary mouse hippocampal neurons in culture. YM-201636 treatment promoted vacuolation of endolysosomal membranes followed by apoptosis-independent cell death. Many vacuoles contained intravacuolar membranes and inclusions reminiscent of autolysosomes. Accordingly, YM-201636 treatment increased the level of the autophagosomal marker protein LC3-II, an effect that was potentiated by inhibition of lysosomal proteases, suggesting that alterations in autophagy could be a contributing factor to neuronal cell death.