WS6 --- β Cell Proliferation Inducer

WS6 is a highly potent and selective small molecule that promotes pancreatic β cell proliferation in rodent and human primary islets, identified by a high-throughput, cell-based screening using rodent pancreatic β cells. It can induce proliferation of mouse R7T1 cells with an EC50 ~0.28 µM, and induce up to 4% of rat β cells and 3% of human β cells to proliferate, with a similar EC50 of 0.4 μM. WS6 induces proliferation of primary rat and human β cells in intact islet format at 0.2-1.0 µM concentration. In the RIP-DTA mouse model of β cell ablation, WS6 demonstrated excellent in vivo effect on normalizing blood glucose and inducing concomitant increases in β cell proliferation and β cell number. Affinity pulldown and kinase profiling studies implicate Erb3 binding protein-1 and the IκB kinase pathway in the mechanism of action of WS6.

Product information

CAS Number: 1421227-53-3

Molecular Weight: 568.59

Formula: C29H31F3N6O3

Chemical Name: N-(6-(4-(2-((4-((4-methylpiperazin-1-yl)methyl)-3-(trifluoromethyl)phenyl)amino)-2-oxoethyl)phenoxy)pyrimidin-4-yl)cyclopropanecarboxamide

Smiles: CN1CCN(CC2=CC=C(C=C2C(F)(F)F)NC(=O)CC2C=CC(=CC=2)OC2=CC(NC(=O)C3CC3)=NC=N2)CC1

InChiKey: FTODTDQFHDJWIQ-UHFFFAOYSA-N

InChi: InChI=1S/C29H31F3N6O3/c1-37-10-12-38(13-11-37)17-21-6-7-22(15-24(21)29(30,31)32)35-26(39)14-19-2-8-23(9-3-19)41-27-16-25(33-18-34-27)36-28(40)20-4-5-20/h2-3,6-9,15-16,18,20H,4-5,10-14,17H2,1H3,(H,35,39)(H,33,34,36,40)

Technical Data

Appearance: Solid Power.

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

Solubility: DMSO up to 100 mM

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:

WS6 was used at 0.5-1 µM concentration in beta cell proliferation assays.

In Vivo:

WS6 was intraperitoneally (IP) dosed to mice 5 mg/kg every other day.

References:

1. Shen W, et al. Small-Molecule Inducer of β Cell Proliferation Identified by High-Throughput Screening. (2013) J Am Chem Soc. In press.

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

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