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MedKoo Cat#: 406176 | Name: Degrasyn
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Description:

WARNING: This product is for research use only, not for human or veterinary use.

Degrasyn, also known as WP1130, is a small molecule that specifically and rapidly down-regulates both wild-type and mutant Bcr/Abl protein without affecting bcr/abl gene expression in chronic myelogenous leukemia (CML) cells. WP1130 was more effective in reducing leukemic versus normal hematopoietic colony formation and strongly inhibited colony formation of cells derived from patients with T315I mutant Bcr/Abl-expressing CML in blast crisis. WP1130 suppressed the growth of K562 heterotransplanted tumors as well as both wild-type Bcr/Abl and T315I mutant Bcr/Abl-expressing BaF/3 cells transplanted into nude mice. WP1130 may be useful in treating CML.

Chemical Structure

Degrasyn
Degrasyn
CAS#856243-80-6

Theoretical Analysis

MedKoo Cat#: 406176

Name: Degrasyn

CAS#: 856243-80-6

Chemical Formula: C19H18BrN3O

Exact Mass: 383.0633

Molecular Weight: 384.27

Elemental Analysis: C, 59.39; H, 4.72; Br, 20.79; N, 10.94; O, 4.16

Price and Availability

Size Price Availability Quantity
50mg USD 450.00 2 Weeks
100mg USD 750.00 2 Weeks
200mg USD 1,250.00 2 Weeks
500mg USD 2,650.00 2 Weeks
1g USD 3,850.00 2 Weeks
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Related CAS #
No Data
Synonym
WP1130; WP-1130; WP 1130; Degrasyn
IUPAC/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
Appearance
white solid powder
Purity
>98% (or refer to the Certificate of Analysis)
Shipping Condition
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition
Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility
Soluble in DMSO, not in water
Shelf Life
>2 years if stored properly
Drug Formulation
This drug may be formulated in DMSO
Stock Solution Storage
0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code
2934.99.9001
More Info
        
Product Data
Product Data
Instruction
View handling instruction
Biological target:
Degrasyn (WP1130) is a cell-permeable deubiquitinase (DUB) inhibitor, directly inhibiting DUB activity of USP9x, USP5, USP14, and UCH37 that also downregulates the antiapoptotic proteins Bcr-Abl (IC50: 1.8 μM) and JAK2.
In vitro activity:
An in vitro analysis using cell lysates was performed to investigate direct DUB inhibition by WP1130. Briefly, untreated Z138 cell lysates were incubated with 5 μmol/L WP1130 or vehicle alone for 1 hour at 37°C, followed by labeling with HA-UbVS. Incubation of cell lysate with WP1130 showed a reduction of HA labeling of the same DUBs as those noted in intact cells (Fig. 4C), suggesting that WP1130 caused direct DUB inhibition. As shown in Fig. 5A, treatment with 5 μmol/L WP1130 reduced the activities of USP9x, USP5, and UCH-L1 by ≥80% (detail in Supplementary Fig. S4). No inhibition was observed against UCH-L3 activity, suggesting that WP1130 may be partly selective. The loss of USP5 activity was confirmed using HA-UbVS labeling, which showed ∼80% reduction in HA labeling on incubation with WP1130 (Fig. 5B). Interestingly, observed a time-dependent increase in cathepsin B activity from the lysates of WP1130-treated cells (Supplementary Fig. S5) was also observed. Reference: Cancer Res. 2010 Nov 15;70(22):9265-76. https://pubmed.ncbi.nlm.nih.gov/21045142/
In vivo activity:
To determine whether degrasyn can reduce the tumorigenicity in a xenograft model, PANC‐1 cells were injected subcutaneously into right flank of mice to construct xenograft mouse model. All xenografted mice were divided in two groups according to degrasyn treatment or not. Tumours in degrasyn‐treated mice were significantly smaller than those in control mice (Figure7A). Similarly, tumour growth was significantly reduced in degrasyn‐treated mice compared with control mice (Figure7B). Furthermore, degrasyn reduced the average tumour volume by 43% compared with negative control (Figure7C). Also, degrasyn treatment resulted in 36% decrease in average tumour weight (Figure7D). Consistent with the results in cell lines, degrasyn reduced the protein levels of WT1 but increased E‐cadherin (Figure7E). Reference: J Cell Mol Med. 2020 Jan; 24(2): 1370–1382. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6991651/
Solvent mg/mL mM
Solubility
DMSO 64.0 166.55
Ethanol 30.0 78.07
Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 384.27 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Recalculate based on batch purity %
Concentration / Solvent Volume / Mass 1 mg 5 mg 10 mg
1 mM 1.15 mL 5.76 mL 11.51 mL
5 mM 0.23 mL 1.15 mL 2.3 mL
10 mM 0.12 mL 0.58 mL 1.15 mL
50 mM 0.02 mL 0.12 mL 0.23 mL
Formulation protocol:
1. Kapuria V, Peterson LF, Fang D, Bornmann WG, Talpaz M, Donato NJ. Deubiquitinase inhibition by small-molecule WP1130 triggers aggresome formation and tumor cell apoptosis. Cancer Res. 2010 Nov 15;70(22):9265-76. doi: 10.1158/0008-5472.CAN-101530. Epub 2010 Nov 2. PMID: 21045142. 2. Kim S, Woo SM, Min KJ, Seo SU, Lee TJ, Kubatka P, Kim DE, Kwon TK. WP1130 Enhances TRAIL-Induced Apoptosis through USP9X-Dependent miR-708-Mediated Downregulation of c-FLIP. Cancers (Basel). 2019 Mar 11;11(3):344. doi: 10.3390/cancers11030344. PMID: 30862047; PMCID: PMC6469024. 3. Li J, Li H, Zhu W, Zhou B, Ying J, Wu J, Zhang H, Sun H, Gao S. Deubiquitinase inhibitor degrasyn suppresses metastasis by targeting USP5-WT1-E-cadherin signalling pathway in pancreatic ductal adenocarcinoma. J Cell Mol Med. 2020 Jan;24(2):13701382. doi: 10.1111/jcmm.14813. Epub 2019 Dec 17. PMID: 31845546; PMCID: PMC6991651. 4. Bartholomeusz G, Talpaz M, Bornmann W, Kong LY, Donato NJ. Degrasyn activates proteasomal-dependent degradation of cMyc. Cancer Res. 2007 Apr 15;67(8):3912-8. doi: 10.1158/0008-5472.CAN-06-4464. PMID: 17440106.
In vitro protocol:
1. Kapuria V, Peterson LF, Fang D, Bornmann WG, Talpaz M, Donato NJ. Deubiquitinase inhibition by small-molecule WP1130 triggers aggresome formation and tumor cell apoptosis. Cancer Res. 2010 Nov 15;70(22):9265-76. doi: 10.1158/0008-5472.CAN-101530. Epub 2010 Nov 2. PMID: 21045142. 2. Kim S, Woo SM, Min KJ, Seo SU, Lee TJ, Kubatka P, Kim DE, Kwon TK. WP1130 Enhances TRAIL-Induced Apoptosis through USP9X-Dependent miR-708-Mediated Downregulation of c-FLIP. Cancers (Basel). 2019 Mar 11;11(3):344. doi: 10.3390/cancers11030344. PMID: 30862047; PMCID: PMC6469024.
In vivo protocol:
1. Li J, Li H, Zhu W, Zhou B, Ying J, Wu J, Zhang H, Sun H, Gao S. Deubiquitinase inhibitor degrasyn suppresses metastasis by targeting USP5-WT1-E-cadherin signalling pathway in pancreatic ductal adenocarcinoma. J Cell Mol Med. 2020 Jan;24(2):13701382. doi: 10.1111/jcmm.14813. Epub 2019 Dec 17. PMID: 31845546; PMCID: PMC6991651. 2. Bartholomeusz G, Talpaz M, Bornmann W, Kong LY, Donato NJ. Degrasyn activates proteasomal-dependent degradation of cMyc. Cancer Res. 2007 Apr 15;67(8):3912-8. doi: 10.1158/0008-5472.CAN-06-4464. PMID: 17440106.
1: Bartholomeusz G, Talpaz M, Bornmann W, Kong LY, Donato NJ. Degrasyn activates proteasomal-dependent degradation of c-Myc. Cancer Res. 2007 Apr 15;67(8):3912-8. doi: 10.1158/0008-5472.CAN-06-4464. PMID: 17440106. 2: Lee KM, Le P, Sieber SA, Hacker SM. Degrasyn exhibits antibiotic activity against multi-resistant Staphylococcus aureus by modifying several essential cysteines. Chem Commun (Camb). 2020 Mar 5;56(19):2929-2932. doi: 10.1039/c9cc09204h. PMID: 32039420. 3: Li J, Li H, Zhu W, Zhou B, Ying J, Wu J, Zhang H, Sun H, Gao S. Deubiquitinase inhibitor degrasyn suppresses metastasis by targeting USP5-WT1-E-cadherin signalling pathway in pancreatic ductal adenocarcinoma. J Cell Mol Med. 2020 Jan;24(2):1370-1382. doi: 10.1111/jcmm.14813. Epub 2019 Dec 17. PMID: 31845546; PMCID: PMC6991651. 4: Peng Z, Maxwell DS, Sun D, Bhanu Prasad BA, Schuber PT Jr, Pal A, Ying Y, Han D, Gao L, Wang S, Levitzki A, Kapuria V, Talpaz M, Young M, Showalter HD, Donato NJ, Bornmann WG. Degrasyn-like symmetrical compounds: possible therapeutic agents for multiple myeloma (MM-I). Bioorg Med Chem. 2014 Feb 15;22(4):1450-8. doi: 10.1016/j.bmc.2013.12.048. Epub 2014 Jan 3. PMID: 24457091; PMCID: PMC4158738. 5: Pham LV, Tamayo AT, Li C, Bornmann W, Priebe W, Ford RJ. Degrasyn potentiates the antitumor effects of bortezomib in mantle cell lymphoma cells in vitro and in vivo: therapeutic implications. Mol Cancer Ther. 2010 Jul;9(7):2026-36. doi: 10.1158/1535-7163.MCT-10-0238. Epub 2010 Jul 6. PMID: 20606045; PMCID: PMC5483974. 6: Nowak Ł, Krajewski W, Dejnaka E, Małkiewicz B, Szydełko T, Pawlak A. Ubiquitin-Specific Proteases as Potential Therapeutic Targets in Bladder Cancer- In Vitro Evaluation of Degrasyn and PR-619 Activity Using Human and Canine Models. Biomedicines. 2023 Mar 2;11(3):759. doi: 10.3390/biomedicines11030759. PMID: 36979739; PMCID: PMC10045593. 7: Garcia-Caballero A, Gadotti VM, Ali MY, Bladen C, Gambeta E, Van Humbeck JF, MacCallum JL, Zamponi GW. A Synthetically Accessible Small-Molecule Inhibitor of USP5-Cav3.2 Calcium Channel Interactions with Analgesic Properties. ACS Chem Neurosci. 2022 Feb 16;13(4):524-536. doi: 10.1021/acschemneuro.1c00765. Epub 2022 Feb 3. PMID: 35113527. 8: Song N, Deng L, Zeng L, He L, Liu C, Liu L, Fu R. USP9X deubiquitinates and stabilizes CDC123 to promote breast carcinogenesis through regulating cell cycle. Mol Carcinog. 2023 Jun 14. doi: 10.1002/mc.23591. Epub ahead of print. PMID: 37314216. 9: Busker S, Page B, Arnér ESJ. To inhibit TrxR1 is to inactivate STAT3-Inhibition of TrxR1 enzymatic function by STAT3 small molecule inhibitors. Redox Biol. 2020 Sep;36:101646. doi: 10.1016/j.redox.2020.101646. Epub 2020 Jul 17. PMID: 32863208; PMCID: PMC7378686. 10: Yan B, Guo J, Wang Z, Ning J, Wang H, Shu L, Hu K, Chen L, Shi Y, Zhang L, Liu S, Tao Y, Xiao D. The ubiquitin-specific protease 5 mediated deubiquitination of LSH links metabolic regulation of ferroptosis to hepatocellular carcinoma progression. MedComm (2020). 2023 Jul 22;4(4):e337. doi: 10.1002/mco2.337. PMID: 37492786; PMCID: PMC10363799. 11: Paemka L, Mahajan VB, Ehaideb SN, Skeie JM, Tan MC, Wu S, Cox AJ, Sowers LP, Gecz J, Jolly L, Ferguson PJ, Darbro B, Schneider A, Scheffer IE, Carvill GL, Mefford HC, El-Shanti H, Wood SA, Manak JR, Bassuk AG. Seizures are regulated by ubiquitin-specific peptidase 9 X-linked (USP9X), a de-ubiquitinase. PLoS Genet. 2015 Mar 12;11(3):e1005022. doi: 10.1371/journal.pgen.1005022. PMID: 25763846; PMCID: PMC4357451. 12: Sen E, Kota KP, Panchal RG, Bavari S, Kiris E. Screening of a Focused Ubiquitin-Proteasome Pathway Inhibitor Library Identifies Small Molecules as Novel Modulators of Botulinum Neurotoxin Type A Toxicity. Front Pharmacol. 2021 Sep 27;12:763950. doi: 10.3389/fphar.2021.763950. PMID: 34646144; PMCID: PMC8503599. 13: Lu L, Liu D, Yang Y, Wang F. [WP1130 relieves septic shock in mice by inhibiting NLRP3 inflammasome activation]. Nan Fang Yi Ke Da Xue Xue Bao. 2022 Dec 20;42(12):1747-1754. Chinese. doi: 10.12122/j.issn.1673-4254.2022.12.01. PMID: 36651241; PMCID: PMC9878421. 14: Chen XH, Xu YJ, Wang XG, Lin P, Cao BY, Zeng YY, Wang Q, Zhang ZB, Mao XL, Zhang T. Mebendazole elicits potent antimyeloma activity by inhibiting the USP5/c-Maf axis. Acta Pharmacol Sin. 2019 Dec;40(12):1568-1577. doi: 10.1038/s41401-019-0249-1. Epub 2019 Jun 13. PMID: 31197245; PMCID: PMC7468578. 15: Ma T, Chen W, Zhi X, Liu H, Zhou Y, Chen BW, Hu L, Shen J, Zheng X, Zhang S, Zhang B, Li H, Liang T. USP9X inhibition improves gemcitabine sensitivity in pancreatic cancer by inhibiting autophagy. Cancer Lett. 2018 Nov 1;436:129-138. doi: 10.1016/j.canlet.2018.08.010. Epub 2018 Aug 15. PMID: 30118840. 16: Chen W, Huang Y, Zhang S, Zheng X, Xie S, Mao J, Cai Y, Lu X, Hu L, Shen J, Dong Y, Chai K. MicroRNA-212 suppresses nonsmall lung cancer invasion and migration by regulating ubiquitin-specific protease-9. J Cell Biochem. 2019 Apr;120(4):6482-6489. doi: 10.1002/jcb.27939. Epub 2018 Oct 18. PMID: 30335901. 17: de Las Pozas A, Reiner T, De Cesare V, Trost M, Perez-Stable C. Inhibiting Multiple Deubiquitinases to Reduce Androgen Receptor Expression in Prostate Cancer Cells. Sci Rep. 2018 Sep 3;8(1):13146. doi: 10.1038/s41598-018-31567-3. PMID: 30177856; PMCID: PMC6120934. 18: Drießen S, Berleth N, Friesen O, Löffler AS, Böhler P, Hieke N, Stuhldreier F, Peter C, Schink KO, Schultz SW, Stenmark H, Holland P, Simonsen A, Wesselborg S, Stork B. Deubiquitinase inhibition by WP1130 leads to ULK1 aggregation and blockade of autophagy. Autophagy. 2015;11(9):1458-70. doi: 10.1080/15548627.2015.1067359. PMID: 26207339; PMCID: PMC4590650. 19: Charbonneau ME, Gonzalez-Hernandez MJ, Showalter HD, Donato NJ, Wobus CE, O'Riordan MX. Small molecule deubiquitinase inhibitors promote macrophage anti- infective capacity. PLoS One. 2014 Aug 5;9(8):e104096. doi: 10.1371/journal.pone.0104096. PMID: 25093325; PMCID: PMC4122495. 20: Liu H, Chen W, Liang C, Chen BW, Zhi X, Zhang S, Zheng X, Bai X, Liang T. WP1130 increases doxorubicin sensitivity in hepatocellular carcinoma cells through usp9x-dependent p53 degradation. Cancer Lett. 2015 Jun 1;361(2):218-25. doi: 10.1016/j.canlet.2015.03.001. Epub 2015 Mar 5. PMID: 25749422.