Degrasyn (WP-1130)

This product is for research use only, not for human use. We do not sell to patients.

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Size	Price	Stock
250mg	$900	Check With Us
500mg	$1420	Check With Us
1g	$2130	Check With Us

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Cat #: V0680 CAS #: 856243-80-6 Purity ≥ 98%

Description: Degrasyn (formerly also known as WP1130) is a novel, potent, and selective small molecule inhibitor of deubiquitinases (DUBs such as USP5, USP14, USP9x, UCH-L1, and UCH37). It also suppresses Bcr/Abl, also a JAK2 transducer without affecting 20S proteasome and an activator of transcription (STAT). It exhibits excellent in vivo antitumor efficacy in Swiss Nu/Nu mice transplanted with K562 tumor cells.

References: [1]. Bartholomeusz GA, et al. Activation of a novel Bcr/Abl destruction pathway by WP1130 induces apoptosis of chronic myelogenous leukemia cells. Blood. 2007 Apr 15;109(8):3470-8.

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Physicochemical and Storage Information
Protocol
Related Biological Data
Stock Solution Preparation
Quality Control Documentation

Molecular Weight (MW)	384.27
Molecular Formula	C19H18BrN3O
CAS No.	856243-80-6
Storage	-20℃ for 3 years in powder formr
Storage	-80℃ for 2 years in solvent
Solubility In Vitro	DMSO: 77 mg/mL (200.4 mM)r
	Water:<1 mg/mLr
	Ethanol: 18 mg/mL (46.8 mM)
Solubility In Vivo	Chemical Name: (S,E)-3-(6-bromopyridin-2-yl)-2-cyano-N-(1-phenylbutyl)acrylamide InChi Key: LIDOPKHSVQTSJY-VMEIHUARSA-N InChi Code: InChI=1S/C19H18BrN3O/c1-2-7-17(14-8-4-3-5-9-14)23-19(24)15(13-21)12-16-10-6-11-18(20)22-16/h3-6,8-12,17H,2,7H2,1H3,(H,23,24)/b15-12+/t17-/m0/s1 SMILES Code: O=C(N[C@H](C1=CC=CC=C1)CCC)/C(C#N)=C/C2=NC(Br)=CC=C2
SMILES Code	O=C(N[C@H](C1=CC=CC=C1)CCC)/C(C#N)=C/C2=NC(Br)=CC=C2
Synonyms	WP 1130; Degrasyn; WP1130; WP-1130;

Protocol	In Vitro	In vitro activity: In addition to inducing rapid down-regulation of Bcr/Abl without affecting Bcr or c-Abl, WP1130 also regulates the stability of Jak2 and c-Myc without affecting other kinases (HER1, HER2, c-Kit, FAK, ERK1, ERK2, Akt, Btk, Src and Src-related kinases) or transcription factors (wild-type p53, STAT1, STAT3, STAT5, c-Jun, NF-κB, and Max). Unlike adaphostin and Trisenox, WP1130 induces down-regulation of Bcr/Abl within 60 minutes. WP1130 is more effective in inducing apoptosis of myeloid and lymphoid tumor cells with IC50 of ~0.5-2.5 μM compared with normal CD34+ hematopoietic precursors, dermal fibroblasts, or endothelial cells with IC50 of ~5-10 μM. WP1130 (5 μM) specifically and rapidly down-regulates both wild-type and T315I mutant Bcr/Abl protein without affecting bcr/abl gene expression or engaging the proteasomal degradation pathway in chronic myelogenous leukemia (CML) cells, accompanied by induction of apoptosis. WP1130 is more effective in reducing leukemic cell colony formation compared with normal progenitor cells, and effective against primary leukemic cells harboring the T315I mutation. WP1130 induces rapid proteasomal-dependent degradation of c-Myc protein in MM-1 multiple myeloma and other tumor cell lines, correlated with tumor growth inhibition. Unlike AG490, WP1130 acts as a partly selective deubiquitinase (DUB) inhibitor to induce a rapid and marked accumulation of polyubiquitinated (K48/K63-linked) proteins into juxtanuclear aggresomes without affecting proteasome activity. WP1130 (5 μM) directly inhibits DUB activity of USP9x, USP5, USP14, UCH-L1, and UCH37, but not UCH-L3, resulting in downregulation of antiapoptotic and upregulation of proapoptotic proteins, such as MCL-1 and p53. Kinase Assay: Degrasyn (WP1130) is a cell-permeable deubiquitinase (DUB) inhibitor, directly inhibiting DUB activity of USP9x, USP5, USP14, and UCH37. Degrasyn has been shown to downregulate the antiapoptotic proteins Bcr-Abl and JAK2. Cell Assay: Cells (BV173, BV173R, K562, and BaF/3) are treated with increasing concentrations of WP1130 (0.08-10 μM) in 96-well plates. Plates are incubated at 37 °C for 72 hours, after which 20 μL of MTT reagent is added, and the plates are incubated at 37 °C for another 2 hours. Cells are lysed with 100 μL lysis buffer (20% sodium dodecyl sulfate [SDS] in 50% N, N-dimethylformamide adjusted to pH 4.7 with 80% acetic acid and 1 M hydrochloric acid; final concentration of acetic acid is 2.5% and hydrochloric acid is 2.5%) and incubated for 6 hours. The optical density of each sample at 570 nm is determined with a SPECTRA MAX M2 plate reader.
	In Vivo	Administration of WP1130 inhibits the growth of K562 tumors as well as both wildtype Bcr/Abl and T315I mutant Bcr/Abl-expressing BaF/3 cells transplanted into nude mice. Consistent with the down-regulation of c-Myc, WP1130 displays potent inhibitory activity against A375 melanoma tumors established in nude mice.
	Animal model	Swiss Nu/Nu mice transplanted with K562 tumor cells, BaF/3wt cells, or BaF/3/T315I cells
	Formulation	Formulated in solution of 1:1 dimethylsulfoxide to polyethylene glycol 30
	Dosages	40 mg/kg/day; i.p. injection

These protocols are for reference only. InvivoChem does not independently validate these methods.

Related Biological Data

WP1130 reduces the growth of CML tumors and Bcr/Abl-expressing cells in nude mice. Blood. 2007 Apr 15;109(8):3470-8.

Down-regulation of Bcr/Abl protein by WP1130 is not associated with changes in Hsp70 and is not suppressed by protease inhibition. Blood. 2007 Apr 15;109(8):3470-8.

WP1130 reduces the viability of cells expressing wild-type and mutant Bcr/Abl. Blood. 2007 Apr 15;109(8):3470-8.

Preparing Stock Solutions

Solvent volume to be added	Mass (the weight of a compound)
Mother liquor concentration	1mg	5mg	10mg	20mg
1mM	2.6023 mL	13.0117 mL	26.0234 mL	52.0467 mL
5mM	0.5205 mL	2.6023 mL	5.2047 mL	10.4093 mL
10mM	0.2602 mL	1.3012 mL	2.6023 mL	5.2047 mL
20mM	0.1301 mL	0.6506 mL	1.3012 mL	2.6023 mL

Quality Control Documentation	Select Batch Purity ≥ 98% COA MSDS NMR HPLC

The molarity calculator equation

Mass(g) = Concentration(mol/L) × Volume(L) × Molecular Weight(g/mol)

Mass

Concentration

Volume

Molecular Weight*

The dilution calculator equation

Concentration_(start) × Volume_(start) = Concentration_(final) × Volume_(final)

This equation is commonly abbreviated as: C₁ V₁ = C₂ V₂

Concentration_(start)

Volume_(start)

Concentration_(final)

Volume_(final)

Step One: Enter information below

Dosage mg/kg Average weight of animals g Dosing volume per animal µL Number of animals

Step Two: Enter the in vivo formulation

%DMSO + % + %Tween 80 + %ddH₂O

Calculation Results:

Working concentration: mg/ml;

Method for preparing DMSO master liquid: mg drug pre-dissolved in µL DMSO(Master liquid concentration mg/mL) ,Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.

Method for preparing in vivo formulation: Take µL DMSO master liquid, next add µL PEG300, mix and clarify, next add µL Tween 80,mix and clarify, next add µL ddH₂O,mix and clarify.

Note:

(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.