YM-201636

YM-201636 is an inhibitor of retroviral budding and PIKfyve-catalyzed PtdIns(3, 5)P2 synthesis, and can also halt glucose entry by insulin in adipocytes. YM-201636 almost completely inhibited basal and insulin-activated 2-deoxyglucose uptake at doses as low as 160 nM, with IC(50)=54+/-4 nM for the net insulin response. Insulin-induced GLUT4 translocation was partially inhibited at substantially higher doses, comparable to those required for inhibition of insulin-induced phosphorylation of Akt/PKB. In addition to PIKfyve, YM-201636 also completely inhibited insulin-dependent activation of class IA PI 3-kinase.

Product information

CAS Number: 371942-69-7

Molecular Weight: 467.48

Formula: C25H21N7O3

Synonym:

YM 201636

YM201636

YM-201636

Chemical Name: 6-amino-N-(3-(4-(4-morpholinyl)pyrido(3',2'-4,5)furo(3,2-d)pyrimidin-2-yl)phenyl)-3-pyridinecarboxamide

Smiles: NC1=CC=C(C=N1)C(=O)NC1=CC(=CC=C1)C1N=C(C2OC3=NC=CC=C3C=2N=1)N1CCOCC1

InChiKey: YBPIBGNBHHGLEB-UHFFFAOYSA-N

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)

Technical Data

Appearance: Solid Power.

Purity: ≥98% (or refer to the Certificate of Analysis)

Solubility: Soluble in DMSO, not in water

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis

Storage Condition: Dry, dark and -20 ^oC for 1 year or refer to the Certificate of Analysis.

Shelf Life: ≥12 months if stored properly.

Stock Solution Storage: 0 - 4 ^oC for 1 month or refer to the Certificate of Analysis.

Drug Formulation: To be determined.

HS Tariff Code: 382200

How to use

In Vitro:

Acute treatment of cells with YM-201636 shows that the PIKfyve pathway is involved in the sorting of endosomal transport, with inhibition leading to the accumulation of a late endosomal compartment and blockade of retroviral exit. The yeast orthologue of PIKfyve, Fab1, is found to be insensitive to YM-201636 (IC50>5 μM). YM-201636 does not inhibit a type IIγ PtdInsP kinase even at 10 μM and inhibits a mouse type Iα PtdInsP kinase with an IC50>2 μM. YM-201636 almost completely inhibits basal and insulin-activated 2-deoxyglucose uptake at doses as low as 160 nM, with IC50=54 nM for the net insulin response. YM-201636 also completely inhibits insulin-dependent activation of class IA PI 3-kinase. At low doses (10-25 nM), YM-201636 inhibits preferentially PtdIns5P rather than PtdIns(3, 5)P2 production, whereas at higher doses, the two products are similarly inhibited. YM-201636 at 160 nM inhibits PtdIns5P synthesis twice more effectively compared with PtdIns(3, 5)P2 synthesis. MDCK cells treated with YM-201636 accumulate the tight junction protein claudin-1 intracellularly. YM-201636 treatment blocks the continuous recycling of claudin-1/claudin-2 and delays epithelial barrier formation.

References:

1. Fernandes F, Chen K, Ehrlich LS, Jin J, Chen MH, Medina GN, Symons M, Montelaro R, Donaldson J, Tjandra N, Carter CA. Phosphoinositides direct equine infectious anemia virus gag trafficking and release. Traffic. 2011 Apr;12(4):438-51. doi: 10.1111/j.1600-0854.2010.01153.x. Epub 2011 Feb 1. PubMed PMID: 21176037; PubMed Central PMCID: PMC3064743.
2. Sbrissa D, Ikonomov OC, Filios C, Delvecchio K, Shisheva A. Functional dissociation between PIKfyve-synthesized PtdIns5P and PtdIns(3,5)P2 by means of the PIKfyve inhibitor YM201636. Am J Physiol Cell Physiol. 2012 May 23. [Epub ahead of print] PubMed PMID: 22621786.
3. Dukes JD, Whitley P, Chalmers AD. The PIKfyve inhibitor YM201636 blocks the continuous recycling of the tight junction proteins claudin-1 and claudin-2 in MDCK cells. PLoS One. 2012;7(3):e28659. Epub 2012 Mar 1. PubMed PMID: 22396724; PubMed Central PMCID: PMC3291620.

Products are for research use only. Not for human use.