WS6inducer of β cell proliferation CAS# 1421227-53-3 |
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| Cas No. | 1421227-53-3 | SDF | Download SDF |
| PubChem ID | 71566751 | Appearance | Powder |
| Formula | C29H31F3N6O3 | M.Wt | 568.59 |
| Type of Compound | N/A | Storage | Desiccate at -20°C |
| Solubility | DMSO : ≥ 100 mg/mL (175.87 mM) *"≥" means soluble, but saturation unknown. | ||
| Chemical Name | N-[6-[4-[2-[4-[(4-methylpiperazin-1-yl)methyl]-3-(trifluoromethyl)anilino]-2-oxoethyl]phenoxy]pyrimidin-4-yl]cyclopropanecarboxamide | ||
| SMILES | CN1CCN(CC1)CC2=C(C=C(C=C2)NC(=O)CC3=CC=C(C=C3)OC4=NC=NC(=C4)NC(=O)C5CC5)C(F)(F)F | ||
| Standard InChIKey | FTODTDQFHDJWIQ-UHFFFAOYSA-N | ||
| Standard 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) | ||
| General tips | For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months. We recommend that you prepare and use the solution on the same day. However, if the test schedule requires, the stock solutions can be prepared in advance, and the stock solution must be sealed and stored below -20℃. In general, the stock solution can be kept for several months. Before use, we recommend that you leave the vial at room temperature for at least an hour before opening it. |
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| About Packaging | 1. The packaging of the product may be reversed during transportation, cause the high purity compounds to adhere to the neck or cap of the vial.Take the vail out of its packaging and shake gently until the compounds fall to the bottom of the vial. 2. For liquid products, please centrifuge at 500xg to gather the liquid to the bottom of the vial. 3. Try to avoid loss or contamination during the experiment. |
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| Shipping Condition | Packaging according to customer requirements(5mg, 10mg, 20mg and more). Ship via FedEx, DHL, UPS, EMS or other couriers with RT, or blue ice upon request. | ||
| Description | WS6 is a novel small molecule that promotes β cell proliferation in rodent and human primary islets with EC50 of 0.28 uM(R7T1 cell viability).
EC50 value: 0.28 uM [1]
Target: β cell proliferation agonist
in vitro: WS6 induced up to 4% of rat β cells to proliferate, with an EC50 of 0.4 μM. In the same format, WS6 also induced 3% of human β cells to proliferate, with a similar potency to the rat β cells. WS6 induced R7T1 proliferation in dose response, with EC50 value of 0.28 μM, Proliferation of R7T1 cells, which are cultured in suspension and grow as clusters, was apparent by visible inspection.
in vivo: RIP-DTA mice were fed Dox in the drinking water until the onset of overt diabetes (blood glucose reading >300 mg/dL, typically 4-10 days), at which point Dox treatment was discontinued and treatment with WS6 was initiated (5 mg/kg every other day via intraperitoneal injection). Pharmacokinetic studies with WS6 at 50 mg/kg revealed a CMAX of ～5 μM and T1/2 of ～2 h. Treatment with WS6 caused a progressive reduction of blood glucose over time, starting around 2 weeks. References: | |||||
WS6 Dilution Calculator
WS6 Molarity Calculator
| 1 mg | 5 mg | 10 mg | 20 mg | 25 mg | |
| 1 mM | 1.7587 mL | 8.7937 mL | 17.5874 mL | 35.1747 mL | 43.9684 mL |
| 5 mM | 0.3517 mL | 1.7587 mL | 3.5175 mL | 7.0349 mL | 8.7937 mL |
| 10 mM | 0.1759 mL | 0.8794 mL | 1.7587 mL | 3.5175 mL | 4.3968 mL |
| 50 mM | 0.0352 mL | 0.1759 mL | 0.3517 mL | 0.7035 mL | 0.8794 mL |
| 100 mM | 0.0176 mL | 0.0879 mL | 0.1759 mL | 0.3517 mL | 0.4397 mL |
| * Note: If you are in the process of experiment, it's necessary to make the dilution ratios of the samples. The dilution data above is only for reference. Normally, it's can get a better solubility within lower of Concentrations. | |||||
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WS6 is a small-molecule inducer of β cell proliferation [1].
β cells are a subset of cells in the pancreatic islets and play an important role in regulating glucose homeostasis through the production of insulin [1].
WS6 is a small-molecule inducer of β cell proliferation. In mouse β cell line R7T1, WS6 induced cell proliferation with EC50 value of 0.28 µM. WS6 was very active in primary human and rodent islets. In primary rat and human β cells, WS6 induced rat β cell proliferation with EC50 value of 0.4 µM and increased 4% of rat β cells and 3% of human β cells to proliferate. In intact islet cultures, WS6 significantly induced proliferation [1]. In cultured human islets, WS6 induced β cell proliferation and also α cell proliferation. However, WS6 didn’t influence the expression of β cell-specific transcription factors and the amount of insulin-positive β cells, which suggested that WS6 didn’t influence β cell differentiation and human islet cell viability [2].
In type 1 diabetes (T1D) mice, WS6 significantly reduced blood glucose and increased β cell proliferation from 3.8% to 6.4% [1].
References:
[1]. Shen W, Tremblay MS, Deshmukh VA, et al. Small-Molecule Inducer of β Cell Proliferation Identified by High-Throughput Screening. J Am Chem Soc, 2013, 135(5): 1669-1672.
[2]. Boerner BP, George NM, Mir SU, et al. WS6 induces both alpha and beta cell proliferation without affecting differentiation or viability. Endocr J, 2015, 62(4): 379-386.
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WS6 induces both alpha and beta cell proliferation without affecting differentiation or viability.[Pubmed:25739404]
Endocr J. 2015;62(4):379-86.
Agents that stimulate human pancreatic beta cell proliferation are needed to improve diabetes mellitus treatment. Recently, a small molecule, WS6, was observed to stimulate human beta cell proliferation. However, little is known about its other effects on human islets. To better understand the role of WS6 as a possible beta cell regenerative therapy, we carried out in-depth phenotypic analysis of WS6-treated human islets, exploring its effects on non-beta cell proliferation, beta cell differentiation, and islet cell viability. WS6 not only stimulated beta cell proliferation in cultured human islets (in agreement with previous reports), but also human alpha cell proliferation, indicating that WS6 is not a beta cell-specific mitogen. WS6 did not change the proportion of insulin-positive beta cells or the expression of beta cell-specific transcription factors, suggesting that WS6 does not alter beta cell differentiation, and WS6 had no effect on human islet cell apoptosis or viability. In conclusion, WS6 stimulates proliferation of both human beta and alpha cells while maintaining cellular viability and the beta cell differentiated phenotype. These findings expand the literature on WS6 and support the suggestion that WS6 may help increase human islet mass needed for successful treatment of diabetes.
