WP1066

貨號 Cat. No.: S2796
規格 Size: 5~200mg
品牌 Brand: Selleckchem

Description

WP1066

Catalog No.S2796

1 Reviews 2 Product Citations

WP1066 is a novel inhibitor of JAK2 and STAT3 with IC50 of 2.30 μM and 2.43 μM in HEL cells; shows activity to JAK2, STAT3, STAT5, and ERK1/2 not JAK1 and JAK3.

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10mM/1mLIn DMSO	USD 158	In stock	0 1 2 3 4 5 6 7 8 9 10
10mg	USD 138	In stock	0 1 2 3 4 5 6 7 8 9 10
25mg	USD 340	In stock	0 1 2 3 4 5 6 7 8 9 10

Distributor Tel: +886-2-2827-1197jimmy@new.abscience.com.tw

Biological Activity

Description	WP1066 is a novel inhibitor of JAK2 and STAT3 with IC50 of 2.30 μM and 2.43 μM in HEL cells; shows activity to JAK2, STAT3, STAT5, and ERK1/2 not JAK1 and JAK3.
Targets	JAK2	STAT3
IC50	2.3 μM ^[1]	2.43 μM ^[2]
In vitro	WP1066 markedly inhibits the growth of HEL cells carrying the JAK2 V617F mutant isoform in a dose-dependent manner with IC20, IC50 and IC80 of 0.8, 2.3 and 3.8 μM. WP1066 at concentrations of 0.5, 1.0, 2.0, 3.0, or 4.0 μM inhibits the phosphorylation of JAK2, STAT3, STAT5, and ERK1/2 without affecting the phosphorylation of JAK1 and JAK3 in erythroid leukemia HEL cells that express the JAK2 V617F isoform. ^[1]WP1066 at concentrations ranging from 0.5 to 3.0 μM inhibits the proliferation of AML colony-forming cells obtained from patients and that of the AML cell lines OCIM2 and K562 in a dose-dependent manner. WP1066 at concentrations of 0.5, 1.0, 2.0, 3.0, or 4.0 μM dose-dependently decreases JAK2 and pJAK2 protein levels as well as downstream phosphorylation levels of STAT3, STAT5, and AKT in OCIM2 and K562 cells. WP1066 at concentrations of 2 μM inhibits OCIM2 cell multiplication by inducing accumulation of cells at the G0-G1 phase of the cell cycle. WP1066 at concentrations of 1, 2, or 3 μM induces apoptosis in both OCIM2 and K562 cells in a dose-dependent fashion by activating procaspase-3 and cleaving PARP. ^[3] WP1066 at concentrations of 5 μM prevents the phosphorylation of STAT3, and at concentrations of 2.5μM WP1066 significantly inhibits cell survival and proliferation in Caki-1 and 786-O renal cancer cells. WP1066 at concentrations of 5 μM suppresses HIF1α and HIF2α expression and VEGF production in Caki-1 and 786-O renal cancer cells. ^[4]
In vivo	WP1066 orally administrated at dose of 40 mg/kg once daily for 19 days significantly inhibits the tumours growth in Caki-1 xenograft mice, with decreased immunostaining of phosphorylated STAT3 and reduced length of CD34-positive vessels. ^[4]
Features	Similar to its parent compound AG490, WP1066 inhibits the phosphorylation of JAK2, but unlike AG490, WP1066 also degraded JAK2 protein.

Protocol(Only for Reference)

Cell Assay: ^[1]

Cell lines	HEL cells carrying the JAK2 V617F mutant isoform, HL60, K562, Raji, PEER, CMK, TM and RHN cells
Concentrations	0 - 6 μM
Incubation Time	72 hours
Method	The 3, [4,5-dimethylthiazol-2-yl]-5-[3-carboxymethoxyphenyl]-2-[4-sulfophenyl]-2H-tetrazolium (MTT) assay is done using an MTT-based cell proliferation/cytotoxicity assay system. Briefly, fresh low-density peripheral blood cells and various cell lines at the logarithmic phase of their growth are washed twice in RPMI 1640 containing 10% FCS and counted in a hemocytometer. Cell viability is assessed by the trypan blue (0.1%) staining method. Equal numbers of viable cells (5 × 10⁴ per well) are incubated in a total volume of 100 μL of RPMI 1640 supplemented with 10% FCS alone or with WP1066 at increasing concentrations; the incubations are continued for up to 72 h in 96-well flat-bottomed plates at 37 °C in a humidified 5% CO₂ atmosphere. Experiments for each condition are done in triplicate. After incubation, 20 μL of CellTiter96 One Solution Reagent are added to each well. The plates are then incubated for an additional 60 min at 37 °C in a humidified 5% CO₂ atmosphere. Immediately after incubation, absorbance is read using a 96-well plate reader at a wavelength of 490 nm.

Animal Study: ^[4]

Animal Models	Caki-1 xenograft mice
Dosages	40 mg/kg
Administration	Orally administrated

References

Clinical Trial Information( data from http://clinicaltrials.gov)

NCT Number	Recruitment	Conditions	Sponsor /Collaborators	Start Date	Phases
NCT01904123	Not yet recruiting	Brain Cancer\|Central Nervous System Neoplasms\|Melanoma\|Solid Tumors	M.D. Anderson Cancer Center\|National Institutes of Health (NIH)	2013-11	Phase 1

Chemical Information

Download WP1066 SDF

Molecular Weight (MW)	356.22
Formula	C₁₇H₁₄BrN₃O
CAS No.	857064-38-1

Storage	3 years -20â„ƒPowder
Storage	6 months-80â„ƒin DMSO
Syonnyms	N/A

Solubility (25°C) *	In vitro	DMSO	72 mg/mL (202 mM)
		Water	<1 mg/mL (<1 mM)
		Ethanol	<1 mg/mL (<1 mM)
* <1 mg/ml means slightly soluble or insoluble. * Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

Chemical Name	(S,E)-3-(6-bromopyridin-2-yl)-2-cyano-N-(1-phenylethyl)acrylamide

Preparing Stock Solutions

Stock Solution (1ml DMSO)	1mM	10mM	20mM	30mM
Mass(mg)	0.35622	3.5622	7.1244	10.6866

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Customer Reviews (1)

Click to enlarge	Rating
	Source	WP1066 purchased from Selleck
	Method	MTT
	Cell Lines	monolayer and adherent CSC
	Concentrations	30, 100, 300 uM uM
	Incubation Time	72 h
	Results	flow cytometric analysis of annexin V-stained cells demonstrated that treatment with the STAT3 inhibitor WP1066 or S3I-201 had a greater effect on the induction of apoptosis in adherent CSCs than in glioma monolayers.